Medicinal Plants in Australia Volume 4

MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary

Flower of the Blackbean, Castanospermum australe. (Courtesy Tony J Young)


Cheryll J Williams

ROSENBERG

First published in Australia in 2013 by Rosenberg Publishing Pty Ltd PO Box 6125, Dural Delivery Centre NSW 2158 Phone: 61 2 9654 1502 Fax: 61 2 9654 1338 Email: [email protected] Web: www.rosenbergpub.com.au Copyright © Cheryll J. Williams 2013 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher in writing. National Library of Australia Cataloguing-in-Publication data: Author: Williams, Cheryll. Title: Medicinal plants : an antipodean apothecary / Cheryll J. Williams. Print ISBN: 9781922013507 (hbk) Epdf ISBN: 9781925078084 Series: Medicinal plants in Australia ; v. 4 Notes: Includes bibliographical references and index. Subjects: Medicinal plants--Australia. Materia medica, Vegetable--Australia. Dewey Number:

615.321

Printed in China by Everbest Printing Co Limited

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Contents Foreword: Brendan Lepschi 7 Introduction: Re-evaluating the Past – Herbs for the Future 8 1 Flowers of the Materia Medica 18 A Potent Floral Pharmacy 19 Opium Extraction 22 Cardioactive Herbs 24 The Medicinal Rose 29 The Aromatic Rose 31 Remedies from Rosehips 32 Multipurpose Rose Remedies 35 Fragrance and Flavourings in Pharmacy 40 Table 1.1 Overview of the main essential oil yielding herbs and spices with flavouring qualities that are utilised in pharmacy 42 2 Asteraceae: Daisies of the Apothecary 47 The Garden Apothecary 47 A Wound-wort of Distinction: Bellis perennis 48 Analgesic Daisies 51 Table 2.1 Summary of investigations into ‘daisy’ herbs of medicinal value from the genera Acmella, Spilanthes and Wedelia 55 Beach Sunflowers and Singapore Daisies 59 Classic Chamomile 66 A Complex Essential Oil 70 Dandelion: a Famed Liver Tonic 70 A Traditional Anticancer Herb 74 Marigolds: Treasure in the Garden 77 Tagetes: American Marigolds 83 Stinking Roger: an Insecticidal Import 86 3 Validating Bush Medicines 90 Native Antibacterials 91 Pterocaulon: A Fragrant Wound Remedy 96 Plectranthus: Aromatic ‘Native Mints’ 98 Table 3.1 Summary of traditional uses of medicinal Plectranthus 101 Antifungal Plectranthus 103 Sneezeweeds 105 Headache Vines 110 An Aromatic Irritant: Tickweed (Cleome viscosa) 114 A Forgotten Herb: the Medicinal Pigweed 118 Buckthorn: a Native Source of Aesculin 123 A Renewed Interest in Native Flora 131 Table 3.2 Overview of Australian plants examined for biological properties in recent scientific literature that are of interest for medicinal purposes 132

4 New Roles for Old Remedies 137 Centella: Ancient Remedy for the Modern World 137 A Remarkable Therapeutic Repertoire 138 Circulatory and Cardiovascular Support 141 A Neuroprotective Agent 144 Table 4.1 Summary of recent investigations of Centella asiatica and its active components 147 Remedies for Recollection 150 Leprosy: Disease and Disfigurement 152 The Leprous Affliction 156 Leprosy Treatment 159 The Legendary Chaulmoogra 161 Achariaceae in Northern Australia 166 Cyanide in Pangium 168 New Roles for Chaulmoogra Oil? 169 Hydnocarpus: Flavonoids of Pharmacological Value 171 Herbal Drugs with Activity Against Mycobacteria 175 Australian Antimycobacterial Candidates 180 Table 4.2 Plants with antimycobacterial potential that are found in Australia (native or naturalised), and closely related native species 184 5 Earth Medicine: A Mineral Pharmacy 193 Antibiotics: The Dirt on Microorganisms 195 Antibacterial Earth 202 Antibacterial Metals 205 Earth as a Poison Antidote 211 Clay for Enterotoxins 214 A Dietary Detoxicant? 219 Drug–Clay Interactions 225 Table 5.1 Summary of clay types used in pharmacy and drug delivery systems 226 Contaminant Considerations 229 Soil Science: A New Look at Urban Earth 237 A Purification Effect 238 Into the Unknown: Microbes for the Future 243 6 A Desire for Dirt? 245 Ancient Art in an Ancient Landscape 245 Ornamentation and Display 246 Mines from Prehistory 251 Ancient Earth 253 Medicinal Muds 255 Mineral Spas 257 Dirt in the Diet? 261 Mineral Matters 264 Table 6.1 White Clay and termitaria samples from the Northern Territory 266 Table 6.2 Summary of Australian clay resources

utilised by Aboriginal people 266 The Downside of Clay Ingestion 269 Parasites from Poo 275 Bugs, Bacteria and the Immune System 278 A Parasite that Influences Behaviour? 283 Medicinal Mycobacteria 285 Therapeutic Earthworms 286 7 Arid Landscapes: Medicinals and Aromatics from the Desert 291 Boobialla Bush Tucker 293 Bastard Sandalwood: Fragrance from the Desert Termite Mounds: Underpinning Ecosystems 277 Precious Resources 306 A Poisonous Mystery 309 Desert Herbals 312 Table 7.1 Summary of the medicinal uses of Eremophila 313 Eremophila longifolia: A Variable Essential Oil 320 A Focus on Antimicrobials 321 Verbascoside: A Versatile Pharmacological Agent 325 Tribe Myoporeae: Intriguing Chemical Complexity 327 Table 7.2 A brief summary of the major chemical components in the Myoporaceae 327 Eeremophilanes from the Asteraceae 329 Dodonaea: A Rather Remarkable Continental Pioneer 331 Table 7.3 Medicinal use of the Dodonaea genus: antimicrobial and healing properties 334 Table 7.4 Additional medicinal uses of the Dodonaea genus 335 8 Ancient Drugs in a Modern World 340 Sorcerous Solanaceae 342 Medicinal Solanaceae 345 The Black Henbane (Hyoscamus niger) 348 Stramonium in Australia 349 Old Herbs for New Drugs 355 Table 8.1 Solanaceae herbs utilised as medicinal plants or for drug production 355 A Modern Market 358 Physostigmine: From Poison to Invaluable Medicine 360 The Infamous ‘Ordeal Bean of Old Calabar’ 361 Discovery of a Miracle Drug 362 Drugs for Memory and Warfare 364 9 Pituri: A Mysterious Narcotic 369 An Outback Drug Plant 372 Pituri: Trade Across a Continent 373 The Problem of Identification 374 The Poison Puzzle 375 Discovery of a Mydriatic and Intoxicant 383 Duboisine or Atropine: the Commercial Market 386 Alkaloid Conundrums 388 A Native Drug for the War Effort 393

The Puzzle of Chemical Variation 395 Table 9.1 Duboisia species and the main chemical constituents of pharmacological interest 398 Table 9.2 Australian Solanaceae and their alkaloidal constituents 399 A Toxic Harvest 400 Success … and Failure: The Australian Experience 400 A Matter of Overseas Development 401 10 Tobacco Tales 403 Wild Tobacco 403 Table 10.1 Australian Nicotiana: distribution, use and chemistry 407 Tobacco as Medicine 408 Risky Business 414 Table 10.2 Summary of the Symptoms of Nicotinic Acid Poisoning 416 A Local Tobacco Trade 418 Native Campanulaceae 422 11 Steroids from Yams 432 Dioscorea: Steroidal Substances 432 A Wild Harvest Table 11.1 The Dioscorea genus as a source of diosgenin and herbal medicines 434 Folk Healing Traditions Table 11.2 Traditional medicinal uses of Dioscorea yams 437 Natural Anticholesterol Agents? 440 Anticancer Yams 444 Alternative Steroid Resources 447 12 K angaroo Apples and Blackberry Nightshades 451 Solasodine for Steroid Production 452 Australian Kangaroo Apples 454 Table 12.1 Summary of Important Medicinal and Toxic Glycoalkaloids in Common Solanaceae 455 The Feral Devil’s Fig 458 The Blackberry Nightshades 462 Table 12.2 Summary of the medicinal uses of Solanum nigrum in different cultures 466 Neurological Influences 469 Anticancer Solanaceae 472 White Nightshade 474 Table 12.3 Traditional Chinese medicine anticancer preparations utilising Solanum nigrum 475 A Curative Anticancer Cream 475 More Medicinal Solanum 481 Table 12.4 Research into additional medicinal uses of the Solanum genus 482 Cestrum, Calcium and Vitamin D 487 Resources 491 Index 541

Foreword As botanists working in a national scientific research institution, my colleagues and I receive many queries from the general public. One of the most frequent areas of enquiry relates to the uses of Australian plants by humans, either for ornament, food or, more significantly, their toxic or medicinal qualities. The last subject has always been a difficult one to respond to, due to the dearth of recent, reliable information. Information on the medicinal properties of Australian plants does exist, but it is widely scattered throughout the scientific and popular literature and as such is not readily available. At least that was the case, until Cheryll Williams embarked upon her ambitious and impressive series, Medicinal Plants in Australia. I first became aware of Cheryll and her work in 2008, when I received an enquiry from her regarding scientific name changes in the Myrtaceae. Thankfully this is an area in which I have some expertise (as opposed to medicinal plants, of which I am largely ignorant), and I was able to help. I also referred her to the Australian Plant Census (APC), a national, collaborative project managed on behalf of the Australian taxonomic botany community by my home institution, the Australian National Herbarium. There began a fruitful and enjoyable relationship; I was impressed and pleased that Cheryll went to such effort to ensure accuracy in a subject (plant taxonomy and nomenclature) that many authors seem content to ignore. As Cheryll mentioned in the first volume of Medicinal Plants in Australia: ‘It [plant taxonomy and nomenclature] is an extraordinarily complex subject … and can drive one to distraction’. I may not always have been able to answer her queries with absolute certainty, the fluid nature of taxonomy and differing opinions negating a definitive answer in some cases; nonetheless, for the most part I like to think I have helped prevent Cheryll from sliding into complete despair and despondency when wrestling with the concepts I and my fellow taxonomists are responsible for generating. When the first volume appeared, I was amazed at the scope and depth of the information presented. My knowledge of medicinal plants is limited at best, and I had no idea of the number of species in the Australian flora which have known or suspected medicinal properties. I had initially thought that Cheryll was intending to publish a single, stand-alone volume, but I

soon realised that there was far, far more to this subject than I had imagined. Cheryll’s careful research and collation of this otherwise scattered information makes for authoritative and entertaining reading. There is the danger that such works may lean too far towards a popular interpretation and sacrifice accuracy for readability, or alternatively tend towards overt and unnecessary detail. Medicinal Plants in Australia is neither of these. The information presented is clear, concise and (most importantly) reliable, referenced as it is to the large scientific literature on this subject and interpreted by someone who is an authority in the field. Through regular email exchanges, I also became aware of the enormous amount of effort required to see each subsequent volume through to fruition and I found myself keenly anticipating the arrival of each new volume. However, in my case it was more a matter of pleasant satisfaction at seeing the finished work, as opposed to exhausted relief at having completed another huge undertaking! Even when struggling under the weight of proofreading, chasing obscure references or interpreting my responses to her queries(!), Cheryll manages an enviably cheerful outlook. I always look forward to the snippets of news from her north Queensland home that often accompany a query or an update on the status of the next volume: newly hatched cassowary chicks in the backyard, three metres of rain falling in five minutes, flying foxes on the back verandah, all things quite foreign to someone in cool, dry Canberra!

Medicinal Plants in Australia is a work that sits prominently in the libraries of both the Australian National Herbarium and the Australian National Botanic Gardens here in Canberra; no doubt it has also found a place in many other libraries in Australia and overseas, as well as on the shelves of anyone interested in Australian plants. It is a work that speaks of the drive, determination and passionate interest of its author, and one that I am very pleased to have been involved with in some small way. Brendan Lepschi Curator, Australian National Herbarium Canberra, 2013

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Introduction

Re-evaluating the Past – Herbs for the Future We live in a world where technological advancement reigns supreme – each day bringing tidings of great strides in the scientific world and quite remarkable innovative technologies. Yet, such innovations are not the mainstay of herbal medicine – and perhaps this is rightly so, for the knowledge that underpins this profession is many centuries old and based on an irreplaceable wealth of clinical experience. This does not preclude the profession from enjoying the benefits that new technologies bring – innovative advances have been made in the extraction, purification and maintenance of the integrity of herbal medicines. Indeed, today we have the choice of a wealth of

remedies, the access to which was once quite restricted. Yet there is the challenge of maintaining the integrity of the knowledge that has been handed down, and to build wisely upon the traditions bequeathed to us from the past. It is a journey that is full of surprises, not because of what we leave behind – but because so many of these old traditions are being validated. In the 1900s, great advances in chemical science were accompanied by some less-than-complimentary views regarding the value of plant-based medicinal products. Strangely enough, this is no less true today. This was reflected in a lack of appreciation of Australia’s floral resources – an attitude that, until relatively recently, endured in many scientific circles. A love of science and innovation leaves many with the desire to seek brighter horizons, with a seemingly old, outdated past relegated to the vaults of disinterest. This perception, unfortunately, leaves many with a lack of appreciation of the great achievements upon which our world is built. In the late 1800s Sir Joseph Hooker made a rather cynical comment about the future of herbal medicine in his introductory essay on the Flora of Australia (then appended to the Flora of Tasmania): I have not alluded to pharmaceutical plants: such may exist, and multitudes of the weeds, seeds and roots of Australia will no doubt enjoy a more or less substantial reputation as drugs for a period, and then be consigned to oblivion. This is the pharmaceutical history of the plants of all countries that have long been inhabited by civilised man, and Australia will form no exception to them, the fact being that of the multitude of names of plants that appear in Pharmacopoeias, the number of really active and useful plants is extremely small.

Red Rock Heart (original artwork courtesy Peter Brooke). In this volume we get to glimpse the greater continental landscape upon which the floral images of discovery are painted. They were not only found in the coastal fringes or the tropical northern jungles. Those searching for medicinal plants trekked across inhospitable territories far inland – a great adventure that resulted in some rather dramatic discoveries that were to rival some indispensable European drugs of the time. 8

Re-evaluating the Past – Herbs for the Future

This perspective was fairly widespread – a sceptical belief that persisted throughout the twentieth century. Sir Joseph was incorrect on a couple of counts. Firstly, there are cultures with successful traditional medicine systems that have evolved a high degree of clinical competency in herbal therapies. Traditional Chinese and Indian Ayurvedic medicine are among the most successful of these, with an excellent reputation for efficacy. There are many other respected traditions that continue to be practiced – Indonesian Jamu, Japanese Kampo, Thai and Korean traditional medicines. An intriguing testament to their validity is the fact that modern drug companies have acquired numerous pharmacological ‘leads’ from these traditional pharmacopoeias. Everyday, a vast variety of herbs continue to be investigated with the ultimate aim of producing new drugs. Secondly, the range of useful plant-based chemicals is extremely diverse. The evaluation of their pharmacological activity continues to inspire numerous discoveries every year. A remarkable diversity of journals, which are devoted to these chemical discoveries, readily attest to this. On the other hand, Hooker’s observations on the lack of interest regarding the development of medicinal plants in clinical practice was, unfortunately, all too accurate. The discovery of antibiotics and synthetic chemistry in the early to mid 1900s led many to blindly invest their faith in the new ‘magic bullet’ era of pharmaceuticals that had arrived. Only much later would the unhappy consequences of the prolonged use of many of these drugs become apparent – and their detrimental side-effects truly become appreciated. The evolution of drug-resistant strains of microbes presents an even more worrying problem for the future. It is these areas of concern regarding drug safety that has led to a greater willingness to support herbal medicine traditions. Almost a century after Hooker published his criticism, the words of the distinguished American Professor Norman Farnsworth illustrate a far different perspective on plant-based medicinals. The low incidence of toxic reactions was deemed worthy of particular comment: There are many proponents of traditional medicine who maintain that the use of decoctions, infusions and/or Galenical preparations of botanicals is the most highly developed form of drug-taking that is desirable or

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necessary. In many instances I am inclined to support this opinion. It is clear to practically everyone what the consequences of continued use of synthetic drugs (including purified natural products of known structure) are, in the way of producing undesirable and/or toxic effects. In the United States, as well as elsewhere, there is a growing sentiment in favour of a return to the use of effective crude botanicals for the treatment of some diseases. Much of this sentiment arises out of knowledge that, at least in the United States, synthetic drugs lead to iatrogenic disease. This has cost the American public about $2 billion annually in additional health care funding. An average hospital stay is increased by 3–5 days owing to these drug-induced side-effects. Although it is difficult to acquire hard data relative to documentation of the incidence of adverse effects due to Galenical forms of medicinal plants (indeed, such data may not exist), it is generally felt by most persons knowledgeable in the use of traditional medicine that side-effects are rarely encountered (Farnsworth 1980).

This was written around three decades ago – and little has changed. Despite remarkable advances in diagnostic tests, scanning technology and drug delivery systems, the medical system crumbles from within. In many places the incidence of iatrogenic disease has risen, the quality of patient care diminished, and continued crises occur with regard to hospital waiting lists and emergency care. Indeed, the basic practice of medicine has come to rely on the provision of drugs as its mainstay – and many physicians have little time to address other factors leading to the ills that plague us, particularly poor lifestyle options and emotional distress. One cannot belittle the beneficial drugs that have resulted from chemical discoveries, nor can it be implied that synthetic developments all exhibit undesirable side effects. However, it is an accepted fact that drug toxicity is a very real part of modern medical practice. It therefore becomes important to realise that these drugs are not the only treatment option available. This is an extremely valid proposition that needs to be given a lot more support in orthodox circles. Many plant-based preparations not only retain their therapeutic validity – investigations continue to expand the knowledge of their benefits, particularly in the area of preventive medicine. However, there are a number of pervasive contradictory perceptions that surround the use of herbal remedies:

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• They are all ‘old folk tales’ and therefore ineffective. • Herbal remedies are innocuous and their use is little more than ‘faith healing’. • Herbal remedies are dangerous, for one reason or another. Yet the past history of drug development is full of ‘old folk tales’ that have resulted in exceptionally effective medicines – some of which continue in use, in one form or another, to this day. In addition, a reliance on potent, sometimes poisonous, plants has certainly been the mainstay of medical practice since time immemorial – and this avenue of investigation continues to be actively researched in the hope of developing new drugs. The cardiotonic drug digitalis from Foxglove herb (Digitalis purpurea), the antihypertensive agent reserpine from the Indian Snakeroot (Rauvolfia serpentina), the anticancer drugs vincristine and vinblastine from the Madagascar Periwinkle (Catharanthus roseus) and taxol from the Pacific Yew (Taxus baccata) are probably the classic examples of successful drug developments – although there are many more natural product discoveries that lie unappreciated. Antifungal, antibiotic and anticancer agents from microbial sources would be among the most prominent. Indeed, 40 per cent of prescription drugs continue to be based on natural products, as are 49 per cent of the new chemical products registered by the American FDA. In the decade between 1983– 1994 around 60 per cent of approved new drugs (including those in anticancer clinical trials) and 78 per cent of new antibacterial agents were natural product-based. Indeed, these resources have been the traditional source of ‘pathfinder compounds’ – the diversity of which continues to be unrivalled by any chemical database in existence (Strobel & Daisy 2003). In some western countries, herbal medicines have progressively acquired a more vital therapeutic role – particularly for those wishing to take more responsibility for their own health. These remedies, in many cases, have already proven to be of inestimable worth in clinical situations. As toxic plants have been largely discarded from the herbalists’ repertoire, the majority of traditional herbal medicines have an excellent track record of use. Because so little is known about these remedies by orthodox medicine, those concerned about drug interactions tend to try

and exclude herbs from the therapeutic equation – often laying the blame for a drug interaction with a herbal medicine and, subsequently, the opportunity for a bit of scaremongering sometimes arises. Which, to be quite honest, seems strangely illogical given the fact that people who are trying to be responsible for their own health care are exactly what the medical profession and the regulatory authorities need. Many forget that it is the drug treatment that is usually the foreign component in the equation.

Aconite (also known as Wolfsbane or Monkshood, Aconitum napellus) is one of the toxic ornamental herbs prized for its wonderful blue flowers. Joseph Maiden mentioned: ‘There is a large demand for the dried root for the preparation of aconite liniment and tincture. The root is very poisonous, and intending growers must be warned not to mistake it for horse-radish’ (Maiden 1892). While its toxic reputation ensured that Aconite was only utilised externally in European traditions, it was valued for centuries in China as an anti-arthritic herbal medicine. This was due to the development of a detoxification process that significantly modified the poisonous qualities of the drug (see Chapter 5 for further details). Aconite was later developed as a valuable homoeopathic remedy that was recommended for the treatment of fevers and inflammation – and emotional disorders characterised by fear.


The chemical complexity of a herb is exceptionally hard to define – and, while we often appreciate the fact that a number of main components are responsible for a remedy’s activity, the entire picture can be elusive. This is not necessarily a problem in herbal medicine, which is based on quality extraction processes that utilise the whole herb – not a single chemical component. The latter is more appropriate for drug development purposes, hence the proliferation of literature emphasising the discovery of new chemical components. While this type of analysis does provide valuable insights into why a plant works, all too often it only hints at the remarkable chemistry that nature has provided. An appreciation of the multifaceted character of a plant remedy is integral to the practice of herbal medicine. There is a need for a change of attitude that supports tried and tested remedies with a good clinical history. There is enormous scope, particularly for immune supportive herbs. There are liver and kidney detoxicants that can mediate drug side-effects, and a range of antidiabetic agents with effective blood sugar regulation attributes. These can often act as a complement to drug therapy and prevent long-term complications. The scope is quite extraordinary and this work provides numerous illustrations with significant future value. It is, in many ways, unfortunate that analytical chemical developments allowed a ‘new’ drug-based form of medicine to replace the old herbal traditions in such an all-encompassing manner. As a result, the knowledge of many remedies from native Aboriginal lore, as well as from traditional European sources, faded over time. In particular, in the 1940s, the perception that there was simply no need for many of the old remedies with the advent of antibiotics became prevalent – even though, at that time, the phenomena of drug-resistant bacteria and individuals who were allergic to penicillin had already been made manifest. Those with an interest in our floral heritage may mourn the loss of so much knowledge, yet we are lucky that the art of herbal medicine, enshrined in the teachings of traditional practitioners, survived at all. The importance of this for mainstream medicine is also little appreciated – for had we lost this vast repository of practical herbal knowledge our scientific world would be bereft of much of its inspiration today. Yet another threat looms. This comes from a

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lack of appreciation by those who are not clinicians with regard to the complicated process of diagnosis and treatment. It is easy to do ‘test tube chemistry’ – but the reality of clinical practice is far different. Experience cannot be replaced by lessons in biochemistry, physiology and drug management, or by bestowing qualifications that ignore the essential need for practical skills based on clinical care. Even the language of modern medicine tends to dehumanise the clinical symptom picture, leaving little appreciation of the suffering and stress associated with many conditions. The problem also lies in the fact that clinicians are not researchers, nor do they usually have the time, resources or finances to undertake such a role. Overall, there are too few of their reports in the literature – and in this way we continually lose an extraordinary amount of irreplaceable knowledge with regard to the properties, mode of preparation and practical use of herbal medicines. Those who would evaluate the literature often fail to acknowledge the vast experience of practitioners in the field. As a result research papers are published that have little true appreciation of the complexity that is inherent in treatment protocols. The addition of an unsympathetic, and often uninformed, bureaucracy to the equation does little to inspire confidence in a fair appraisal of the art of herbal medicine.1 In my own case, I have had proprietary homoeopathic medicines confiscated because they contained yohimbine and I did not have the appropriate permit – even though, as homoeopathics, they were not strictly illegal. However, I was advised that to organise the paperwork would take too long (over ten days) and I risked being fined. It was simply not worth the effort and the goods were destroyed. On another occasion I had sent medicines from Papua New Guinea (where I was residing at the time) to family in Australia. These were confiscated by Customs – even though they had been originally purchased and manufactured in Australia. 1 Indeed, a recent bright bureaucratic idea involved a restrictive ban on plants that contained chemical compounds which could be considered to have potential as illicit ‘drug plants’. The fact that many ornamental plants, a fair number of native species, and quite a few weeds, could fit in this category could easily have criminalised all walks of life – ranging from plant nurseries, botanic gardens and plant collectors, to backyard gardeners. Needless to say, the legislation was variously described as ‘insane’, ‘idiotic’ and ‘insulting’. Assurances that the legislation was only designed to target the illegal drug market were met with a great deal of scepticism (see Kirk 2012).

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Ephedrine: An Invaluable Discovery

Ephedra major subsp. procera. Ephedra plants are fairly unassuming shrubby herbs or small shrubs with twiggy stems. Numerous species contain alkaloids, primarily ephedrine and pseudoephedrine. Official sources are the Chinese species Ephedra sinica, E. distachya and E. equisetina – although species from other countries, such as E. major and E. intermedia, can provide alternative resources.

Ma Huang has an extremely ancient history, with records dated around 3100 BC (some 5,000 years ago) mentioning its use. This remedy was destined to make invaluable contributions to medical science after the discovery of ephedrine from Ephedra sinica in the 1920s by the pharmacologist Ku Kuei Chen. As with many of the truly famous plantderived drugs the herb itself was not destined to achieve notable pharmaceutical fame – it was the chemical ephedrine, which had effects similar to adrenaline, that quickly became approved for use by the American Medical Association in 1926. Importantly, its significant decongestant and antispasmodic effects were suitable for commercial exploitation by drug companies. For the better part of a century this discovery has provided inspiration for pharmaceutical drug derivatives that have earned the industry billions of dollars in revenue – yet few have acknowledged the great value of this humble herb. Indeed, in Australia, its use is banned to the very profession that traditionally deployed the herb for centuries. The term Ma Huang refers to the herb as used in Chinese medicine; it should not be applied to the extracted alkaloids or their various combinations. The integrity of the herbal product relies on the species which is utilised, as well as processing methods and storage conditions. Certainly, the use of the herb is not equivalent to the deployment of specific alkaloids – and the two should not be confused. While the traditional use of the remedy has not generally been associated with toxic reactions, the reputation of the herb suffered when commercial products containing Ephedra were inappropriately formulated and marketed. Particularly worrying was the fact that the isolated alkaloids (ephedrine, norepinephrine) were utilised instead of the herb – a substitution that seriously increased the likelihood of toxicity. It is little appreciated that the pharmacology of Ma Huang is somewhat different from pure ephedrine. Other constituents in the plant (probably flavonoids) interfere with the absorption of alkaloids from the gastrointestinal tract, and this slows down their effect in the body. Compounds are also present that have


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competing actions. For example while the root extract acts as a hypotensive agent, it also contains a hypertensive alkaloid (maokinine). The shoot extract likewise showed a hypertensive action, although there a number of compounds (ephedradines) in the plant which are hypotensive (Izaddoost & Robinson 1987). Traditionally, the mode of preparation is extremely influential and the herbal effect can vary greatly, depending on the processing used. The twigs or stems are employed raw as a diaphoretic, or baked with honey to elicit an anti-asthmatic action. In contrast, the root is a highly effective antihidrotic (acting to stop sweating in fevers, etc). Therefore, for herbal medicine purposes, it is important to evaluate the clinical use of plantbased remedies, rather than the effects of the isolated principles.

 This work tries to marry the old with the new – the debt that new remedies have to old inspirations, and recent innovative applications for age-old herbs. It begins with an emphasis on how important the conventional cottage garden was as a medicinal resource. It was not merely a place for ornamental curiosities, or for the production herbs and spices of culinary value. Numerous medicinal plants were readily cultivated in the early days of European settlement in Australia. While wound-healing herbs for treating infections and fractures predominated, some surprisingly effective remedies for dropsy and heart problems could be found in just about every major garden planting. Some were highly ornamental, a few were nondescript, and others were so common they were simply taken for granted. The important point to remember is that many herbs gained official recognition of their usefulness, much of which has endured to today. Indeed, in some cases research has not only validated their efficacy, it has given these remedies ‘a new life’ in modern therapies. Even so, we need to appreciate the wisdom of the ancient texts and traditions – and there is a surprising level of continuity. Many old herbal texts have provided invaluable drug inspiration –

Ornamental urn advertising the Pure Drugs that were dispensed in Australian apothecaries (EJ Martin’s Chemist, Herberton Historical Village, north Queensland).

Nineteenth-century medicine chest ca.1880 held in the Townsville Museum. (Courtesy Townsville Museum)

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A Walk in Ochre Country (original artwork courtesy Peter Brooke). Medicines can come from some unusual sources. Indeed, ochre has an ancient history of practical, medicinal and artistic use across the world. Mined in Australia since ancient times, its use often holds great cultural significance for Aboriginal people. Coloured ochres have been integral to the execution of historical and modern artworks – as well as possessing significant healing properties with some rather surprising applications.

irreplaceable repositories of a practical wisdom that is not widely appreciated today. There are some fascinating records. Incidents of microbial contamination have resulted in the serendipitous use of antibiotic remedies since ancient Egyptian times. Even beer and bread recipes had a beneficial antibacterial component. There are many tales of the medicinal use of mud, moulds and even remedies from worms that, in reality, have a substantial basis in truth. This extends to the Aboriginal use of ochre, breast milk, urine and saliva as adjuncts to therapy. Indeed, medicine has become so far removed from its origins that many forget that antibiotics originated from moulds and soil microbes. To this day, research chemists regularly investigate these resources in the hope of new discoveries – some of which can be quite unexpected. Certainly this has been the case with the revelation that common soil-transmitted helminth infections (hookworm, roundworm) show significant benefits for the immune system, particularly for the prevention of

autoimmune disease, albeit ‘worms in the system’ would normally be considered highly undesirable. Even the rather odd habit of eating earth has its pros – and cons. The latter can sometimes be linked to environmental issues, with lead and arsenic being foremost among the toxic soil contaminants that have a significant impact on health issues. For better or worse, the use of diverse chemicals has had (and continues to have) an irreversible impact on the world in which we live. Be prepared to be surprised at just how well modern techniques are verifying age-old traditions, and the ramifications for the Australian flora. There have been a number of natives that became famous as drug plants, stories that have been largely forgotten and relegated to the past. They include the native ‘tobaccos’, steroid resources and raw materials for the contraceptive pill. Hopefully this volume will bring their tales to life, and provide an appreciation of how important native resources truly are – and the indispensable place that many common plants and


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Floral Fantasia (original artwork courtesy Lolli Forden, Cairns). Within the vibrant flash of flowers and verdant green foliage, plants retain chemical secrets that may never be truly unravelled by science. There are somewhere between 300,000 and 500,000 different plant species – with merely 15 per cent having been subjected to phytochemical analysis. Even less (6%) have been evaluated pharmacologically. The majority of this analysis has been done on flora of the tropical and subtropical regions, with colder climates remaining largely unexplored –and entire new phytochemical worlds lie hidden within marine environments. The recent discovery of microbial endophytes within plants presents a similar unknown world of potential that may well help explain the medicinal efficacy of many remedies. It is equally surprising to note that, despite the discovery of numerous antibiotics and anticancer agents from microbial sources, only around 1 per cent of the microorganisms visible under a microscope have been cultivated (a necessary part of the identification process) – therefore ‘the microbial universe clearly presents a vast untapped resource for drug discovery’ (Cragg 2012).

‘old folk treatments’ once had as household remedies, and as medicines for the professional apothecary’s practice. There is a lot to appreciate and, as time (and this tome) will show, the ages of discovery, learning and innovation are far from over. Plants are a constant aspect of everyday living that provide an important link between the past and the future. It has been a remarkable tour of discovery into uncharted botanical waters on these antipodean shores. Truly, it is a fascinating story.

Author’s Acknowledgements

Tony Young has been ever reliable with his persistent research efforts, and this volume has been an exceptional undertaking. He deserves many thanks for tracking down numerous hard-to-find images – as well as his painstaking work checking (and rechecking) botanical and chemical names, and

compiling the index. Thanks, also, are due to Shaune Williams and Brigitta Flick for their professional support – and to Anne Savage for her editorial contributions. As always, we have hunted high and low for many of the images that make these volumes such a visual feast – and many thanks are due to David and Scilla Rosenberg for being so patient with the enormous workload involved in such an endeavour. We try our best to contact the authors of any images utilised, even if they are under free-licence, to ensure we have the correct acknowledgements and to express our appreciation of their wonderful efforts. In the main we have been successful, but there are, regrettably, always a few who ‘slip though the net’. We would also like to express appreciation of the exceptional resource that Wikipedia and Wikimedia Commons have become, along with totallyfreeimages. com, and the remarkable contributions they contain. Once again, the efforts of Peter Woodard, Brian Walters and the Australian Native Plants Society (ANPS) have been invaluable. The lovely images of native flora by Craig Nieminski and Russell Cumming also feature in a number of chapters – as do various

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drug plants by Farmer Dodds. In the section on Emu bushes (genus Eremophila, Chapter 7), there are some outstanding contributions by Melburnian that rate special mention. Equally inspirational are the unique artworks of Peter Brooke and Lolli Forden. In addition, access to geological images, courtesy of Mark A Wilson and Rob Lavinsky, were essential for the sections dealing with minerological matters. The botanical expertise of Brendan Lepschi (Australian National Herbarium) has maintained an essential role in ensuring the botanical integrity of much of this work. While a few companies such as Martin & Pleasance, Cathay Herbal and Acuneeds were very generous in their assistance with product images, it was quite puzzling to find that quite a number of Australian companies producing nutritional and herbal medicines declined. Thank you also to the Herberton Historical Village (Atherton Tablelands, north Queensland) for their gracious access to a treasure trove of old herbal and drug paraphernalia – and to The Apothecary of Cairns. On a personal level, mention should be made of the support given by Helen Timmins, Heather Rabbich, Kathryn Collis, Chris Crosland, Jenny Sheppard, Sue Jordan, Bruce Allen, Margaret Young, Joan O’Grady – and my deepest gratitude to the exceptional Dr Sue Cory.

A Perfect Posy (original artwork courtesy Lolli Forden, Cairns). Many common flowering plants have an enduring healing reputation resulting from their medicinal use for millennia. Even today, new research with regard to old remedies is opening a world of therapeutic surprises that continue to validate and enhance their future as medicinal plants.

Continued support by Brigitta Flick and Tony Young for Daintree Wildlife Rescue has seen us successfully struggle through yet another difficult year. Kim and Forest Starr from Hawaii have continued to be unstintingly generous with unrestricted access to their extraordinary image repository.


Erosion: A stark reminder of the consequences of poor environmental management (original artwork courtesy Peter Brooke).

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Chapter 1

FLOWERS OF THE MATERIA MEDICA

This medicine chest has an interesting history. It was originally employed at the London chemist and druggist Thomas Keating & Co, St Paul’s Church Yard, London, 1830–45. Captain Robert Bailey, of the steamship Tartar, acquired it for his voyages carrying Australian wool to England – and later passed it on to relatives in the Dean family, who lived on a farm outside Gulgong, New South Wales. Subsequently, the chest was given to the local pharmacist, Mr DH Dugan – who had it on display in his pharmacy. His son donated the chest to the Powerhouse Museum, Sydney. (Image courtesy Powerhouse Museum)

Until the last century or so, the skilled medical practitioner required a good level of botanical knowledge. Following this tradition, the physicians who initially came to Australian shores brought their own supplies. They were usually intelligent, accomplished scientific men, albeit faced with a new land that they knew nothing about. This hampered the

initial search for native remedies that could be pressed into service as substitutes for common European drugs – although the Eucalypts, Tea Trees and various native aromatic herbs made a good impression. Drugs such as belladonna, hyoscyamine and opium had to be imported – or cultivated. While a few survived in propagation, many did not, and a couple escaped into 18


the wild to prosper and become a perpetual nuisance. Those that simply ran wild included the styptic and antihaemorrhagic remedy Shepherd’s Purse and the anti-asthmatic herb Stramonium. Surprisingly effective remedies could be easily grown in the cottage gardens of the colony – a few were highly ornamental, while others were nondescript. Some were so ubiquitous that they were simply taken for granted. A number provided remedies for dropsy and heart problems, including cardiotonics that were sourced from the delightfully ornamental Foxglove, Lily-of-the-Valley and the Summer and Winter Adonis herbs. Even the Apothecary’s Rose and various poppies would take pride of place in colourful garden displays. With a vast heritage in the utilisation of medicinal plants, the Chinese immigrants later ran their own intriguing pharmacies. Interestingly, they too looked to the native flora to find substitutes where possible and, in many ways, would have had a greater appreciation of its practical therapeutic value than the European community.

A Potent Floral Pharmacy Syrup of Field Poppy

Field Poppy (Papaver rhoeas) is naturalised throughout much of the temperate parts of the Australian content, notably Western Australia (southwest region), South Australia and Tasmania.

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The European Field Poppy (Papaver rhoeas) possesses medicinal attributes, albeit of a minor nature in comparison to its famous relative, the Opium Poppy (P. somniferum). In India the latex from the Field Poppy capsule was considered narcotic and sedative – although it does not contain morphine and the effect is probably due to the presence of other alkaloids, notably rhoeadine. The fresh petals also contain an anthocyanidin (mekocyanin), which is chemically related to the cyanin of red rose petals. They were once a valued colouring agent for wine and pharmaceuticals (Evans 1989). A syrup of Field Poppy petals was officially listed in the 1949 British Pharmaceutical Codex (BPC). Extracts of the petals were considered to have calming, pain-killing, sudorific (sweatpromoting) and mucilaginous properties, hence their use for easing cough and hoarseness. In Turkey the flower syrup provided a tonic for anaemia. Furthermore, the crushed leaves were utilised as a diaphoretic for treating colds and feverish conditions. Some of these effects may be linked to alkaloid components, although one study of an alkaloid-free extract prepared from Field Poppy petals demonstrated sedative activity at a dose of 400 mg/kg (Soulimani 2001). An excellent quality oil, comparable to Olive oil, can also be extracted from the seeds. In the early days of Australian settlement opium was a mainstay of medical practice due to its analgesic and anti-diarrhoeal properties. Laudanum was a common tincture (alcohol-based) opium preparation.1 The formulation originated with a Dr Sydenham of London around 1670. Prior to this, the term ‘laudanum’ had been used to describe the solid opium preparations of the seventeenth century that were official in the early editions of the London Pharmacopoeia. Laudanum tincture, which contained around 10 per cent opium (equivalent to 1% morphine), had the same therapeutic value as opium itself and was widely employed in diarrhoeal and dysenteric disorders. 1 This should not be confused with the resin Ladanum (in some instances mistakenly spelt laudanum) that is sourced from Cistus creticus.

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Numerous Laudanum recipes were concocted. They included a Black Drop or Quaker Laudanum, and a Vinegar of Opium that was around three times the strength of ordinary Laudanum. Paregoric (Camphorated Opium Tincture) was a weaker preparation (about 1/25th less in strength than opium tincture: 0.4 mg/mL) in combination with other ingredients such as Anise oil, Benzoic acid and Camphor (Martin & Cook 1956).2 These opium preparations had substantial potential for toxicity, making the dosage extremely important. Simple errors in the amount used, or the type of preparation, could easily result in an overdose. This has occurred with the use of Opium tincture instead of Paregoric – a mistake that increased the opium intake over 25 times that of the regular dose. The risk of addiction due to the widespread use of Laudanum was equally serious. Symptoms of poisoning were associated with various degrees of euphoria, sedation and respiratory depression, leading to respiratory and cardiac collapse and, possibly, death.

Tincture of Opium, British Pharmacopoeia, 1874.

2 ‘Paregoric’ was an ancient term used in writings on pharmacy and medicine. It described an anodyne (mild pain-killing) or soothing preparation generally employed for the treatment of coughs, nausea and abdominal pain.

Poppies in Australia

The term ‘laudanum’ was coined by Paracelsus to describe a solid type of medicine whose ingredients were a professional secret. (Courtesy Cydone, Wikimedia Commons, Public Domain) Papaver somniferum.

Powdered Opium: prepared by Australian manufacturer Taylors Elliotts & Australian Drug Pty Ltd, Brisbane.

No representatives of the Poppy family (Papaveraceae) are native to Australia – although a number have become naturalised, including the infamous Opium Poppy (Papaver somniferum) which is found throughout New South Wales, Victoria, South Australia and Tasmania. In addition to Papaver somniferum (subsp. somniferum and subsp. setigerum), five other species are listed: Bristle Poppy (P. aculeatum), Pale Poppy (P. argemone), Long-headed Poppy (P. dubium), Rough Poppy (P. hybridum) and the Field Poppy (P. rhoeas).


Very early introductions to the continent included Papaver aculeatum, which was even mistaken for a native inhabitant by researchers. Joseph Bancroft wrote of his interest in Papaver horridum (now P. aculeatum): I have for some years past been anxious to ascertain whether the native poppy contained morphine, but it was not until last August that I was enabled, through the kindness of Mr. J. H. Simmonds, to obtain a supply of the plant. All parts of the plant have a slightly bitter acrid taste. An extract is very poisonous to frogs … I endeavoured to prepare morphine from an extract of this plant according to the method prescribed by the British Pharmacopoeia, but failed to get even a trace of that substance, or indeed of any other substance. Judging from this and from the physiological effect on frogs it would appear that the active principle is not morphine. It is, however, quite as poisonous as morphine (Maiden 1889).

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noted: ‘The seeds yield about 50 per cent. of their weight in oil, and for this article alone it would pay to cultivate the plant in the Colony’. He concluded: An acre of well cultivated poppy plants will yield about half a ton of seed, and from this can be expressed 560lb. weight of oil. The residue makes very good feed for cattle. The oil is inodorous [lacking aroma], and of an agreeable flavour, so that it can be used for domestic purposes, such as salads. Besides this it can be used for a great variety of purposes, and is extensively used in house-painting. Mixed with white lead it leaves a beautiful surface, which does not afterwards change by the action of light into a dirty yellow colour. After the crop is gathered cattle and sheep may be turned into the field to eat the stalks down. Although they may not be considered very fattening, still the sheep will eat them, without any ill effects.

The Opium Poppy is easy to grow, and in the late 1800s it was given consideration as a commercial crop in New South Wales. Fred Turner mentioned its potential value in a review of New Commercial Crops in the Agricultural Gazette of New South Wales: According to [the Statistical Register] the importation of opium into the Colony for the year 1889, amounted to 25,256 lb., valued at £47,915, and the exports to 5,068 lb., valued at £10,734, thus leaving the value of home consumption at £37,181. It would take the produce of about 450 acres to supply the annual demands for opium alone in this Colony. An acre of well cultivated poppy plants would yield from 40,000 to 50,000 capsules, and these will exude under proper treatment from 40 lb. to 50 lb. or even more, of opium, the usual market value of which is from 30s [shillings] to 35s per lb. Farmers in this Colony are now cultivating crops which give them smaller returns, and they might do much worse than put under cultivation an acre or two of the opium poppy. It is only by attending to these ‘small creatures’ that farmers can ever hope to make their calling a more lucrative one. Many of these crops can be harvested at slack times, whilst the ordinary crops are maturing. The poppy plant occupies the land but for a few months of the year – usually about 3½ – so that produce can soon be turned into a marketable commodity (Turner 1891).

If this market encountered problems, then there were a number of other options for the use of the plant. Certainly, it was a suitable oil crop resource, as Turner

Decoction of Poppy capsules, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

The dried poppy capsule has similar properties to opium as an anodyne and narcotic agent, albeit much weaker in effect.

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Opium Extraction

can be substantial variation in quality. Harvesting too early will yield a watery product, whereas collections that are done too late result in a lower alkaloid level. The slices into the capsule must be shallow, as piercing the capsule will let the latex drain inside and it is not recoverable. Poor processing methods or inadequate storage conditions can easily result in degradation of the morphine content. Heroin bottle, originally contained 5 grams of heroin. Heroin (diacetylmorphine) is an opioid drug synthesised from morphine. (Image courtesy author Mpv_51 via WIKI)

Opium latex from capsule. (Courtesy Farmer Dodds, flickr)

The extraction of opium was never an easy task. Raw opium is largely composed of waxes, resins and a variety of inert ingredients that limit the material available for morphine extraction. Poppy capsules contain very small amounts of morphine, that is, 0.18–0.28 per cent. The time of latex collection is important, with peak production occurring 2–3 weeks after flowering (a few days after the petals fall off). Harvesting any earlier, or later, significantly reduces the yield. After the pod ripens following extraction of the latex, it contains no opium. The ripe seed chemistry is equally innocuous, which makes them suitable for cooking purposes or oil production. The official Opium standard, Opium BP, is standardised at 10 per cent morphine, not less than 2 per cent codeine, and thebaine up to 3 per cent. However there are up to 30 other alkaloids in the plant. The papaverine alkaloids (noscapine, narceine and papaverine) are counted among the minor constituents of interest (Evans 2002). While modern production methods utilise the whole plant for solvent-extraction of the alkaloids, the traditional collection process was based on the harvest of the pod latex. This involved the skilful application of shallow incisions in the immature green pod, which had to avoid puncturing the pod or disturbing the seeds inside. An oddity of nature ensures that there is a limited time availability of the latex from the poppy capsule – around 5–10 days after the petals fall off. This is the only time that the mixture of alkaloids suitable for opium production is available – and there

(Below) Raw opium. (Courtesy Eric Fenderson, Public Domain)

Surprisingly, opium continues to have a place in modern medical practice. The effect of opium, which is slower than that of its major constituent morphine, is indicated for intractable diarrhoea as it slows the intestinal transit time, allowing more effective fluid absorption. Opium also has diaphoretic attributes (induces sweating) and can decrease metabolism. Indeed, the latter resulted in its former use (as well as codeine) for the treatment of diabetes. Codeine has milder analgesic and sedative properties, as well as an antitussive effect, hence its incorporation into


numerous cough medicines – although there are some potent preparations on the market, and constipation can be a serious side-effect of prolonged use (Evans 2002).

Wayward Wallabies

Female wallaby and young. (Courtesy Craig Nieminski, flickr)

Medicinal properties of Opium extract, from British Pharmacopoeia, 1934.

Tasmanian poppy crop. (Courtesy Peter Sharman)

Syrup of Poppy, from British Pharmacopoeia, 1874. Poppy capsule-based syrup was once commonly used as an ingredient in cough medicines. However, the alkaloid content was variable with toxic potential that could easily lead to incidents of poisoning in children. Laudanum tincture. Noscapine (narcotine) has antitussive properties, as well as undesirable emetic and nauseant effects. For this reason the compound is removed from tincture preparations, which are known as Denarcotised or Deodorised Tincture of Opium (DTO). This should not be confused with diluted tincture of opium (which should not be abbreviated to DTO), a drug that is utilised for treating opiate withdrawal in newborn babies. (Image courtesy djm55, Wikimedia Commons, Public Domain)

Wallabies in Tasmania have been raiding the local opium poppy crops in times of scarcity – although this does not appear to be motivated by the desire for an opportunistic drug hit. The animals are simply searching for the nutritious seeds within the poppy capsule. However, during their foraging it appears that the wallabies may quite often ingest some poppy alkaloids, although the effect on animals is not the same as the human experience. Maude Grieve (1931) commented: ‘Opium and morphine do not produce in animals the general calmative and hypnotic effects which characterize their use in man, but applied locally, they effectually allay pain and spasm. Owing to the greater excitant action in veterinary patients, the administration of opium does not blunt the perception of pain as effectually as it does in human patients.’ Animal responses to morphine can therefore vary considerably. It has an excitant effect in cats, horses, cattle and swine, and the synthetic codeine-derivative Tramadol is more suited for use as a veterinary analgesic (The MERCK Veterinary Manual, www.

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merckvetmanual.com). The mysterious ‘crop circles’ that have appeared in the poppy fields may therefore be due to wallabies doing a bit of ‘circle hopping’ due to this excitant effect. There are stories of other animals such as sheep and deer behaving in the same manner.

Cardioactive Herbs

Foxglove entry, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

Digitalis tincture. (Courtesy The Apothecary, Cairns)

The lovely Foxglove (Digitalis purpurea), which has long graced cottage gardens, would be considered the most clinically successful of the cardiotonic herbs. While a surprising variety of ornamental herbs have similar cardioactive properties, for various reasons they never achieved the therapeutic success of Foxglove. Although their properties would be little appreciated today, many of these herbs were formerly considered an invaluable part of medical practice.

Foxglove, Digitalis purpurea, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. Foxglove is naturalised in Tasmania – as well as being a garden escapee in New South Wales and Victoria. The cardiotonic properties of Foxglove saw it utilised therapeutically for more than two centuries. Importantly, this elegant herb is the origin of the drug digitalis. Joseph Maiden mentioned that the plant was easily grown as a local crop: ‘The leaves of the Foxglove … are required in both the fresh and dried state. The fresh leaves are used prepare the juice’. In some treatment protocols Adonis (from Adonis species) was alternated with digitalis – possibly because it had cardiac benefits of a different calibre to the latter and, importantly, lacked the cumulative toxicity which could be associated with repeated doses of digitalis. The Summer Adonis or Pheasant’s Eye (Adonis microcarpa, formerly A. annua) favours a temperate climate, particularly South Australia – although it is also present in Western Australia (southwest), New South Wales, and southern Queensland. (Image courtesy Pablo Alberto Salguero Quiles, Wikimedia Commons, CC-by-SA3.0)


25 (Left) Adonis vernalis.

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The Climbing Oleander, Strophanthus gratus. This vine, which has become widely planted as an attractive tropical ornamental, is of particular medicinal interest. Although many species of Strophanthus have cardioactive potential, only S. gratus retains practical value. The seed contains 4–8 per cent ouabain (strophanthin-G), a substance unique among the cardiotonic glycosides that can be easily extracted in a crystallised form. Ouabain exhibits a consistent level of activity, against which the potency of similar substances can be accurately compared – hence its adoption as a reliable test standard for the evaluation of cardioactive drugs.

(Below) Adonis vernalis, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

The Summer Adonis (Adonis microcarpa) and the Winter Adonis (A. vernalis) are two examples that contain glycosides (adonitoxin and cymarin, respectively) which act similarly to those of Strophanthus and Digitalis.3 The Martindale Extra Pharmacopoeia of 1952 provides the following details: ‘Adonis had a digitalis-like action. It slows the heart by stimulating inhibition and it increases diuresis. It is inferior to digitalis in its therapeutic action because of its irregularity of absorption’. It was used as a digitalis substitute in some situations, providing an alternative in cases that were unresponsive to conventional drugs – although its usefulness was limited due to some unpleasant side-effects such as vomiting and diarrhoea – and could be employed in conditions complicated by kidney dysfunction. Adonis also contains the cardiotonic glycoside adonidin, which had an effective local anaesthetic action. This led to its use in solutions for ophthalmic investigations, and for providing pain relief in inflammatory eye disorders such as iritis and iridocyclitis4 (Martindale 1952). 3 Other Adonis species contain similar cardenolides: A. aestivalis, A. aleppica, A. chrysocyanthus and A. sibir – some of which were used as substitutes for the Summer Adonis (Pauli 1995, 1993; Kopp 1992; Mamadov 1986; Maksiutova & Lazareva 1978). 4 Inflammation of the iris (iritis) of the eye, or of the iris and ciliary body (iridocyclitis).

Adonis vernalis, from Peter Squires, Companion to the Latest Edition of the British Pharmacopoeia, London, 1899.

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Cymarin and related compounds (adonin, adonilide) have been isolated from the Amur Adonis (Adonis amurensis) – the roots of which have provided a heart tonic in Chinese medicine. It was recommended for the treatment of congestive heart failure, as well as being an effective diuretic and tranquilliser. Interestingly, an extract preparation developed in Manchuria has been used clinically in the treatment of rheumatic heart disease (Duke & Ayensu 1985). (Image courtesy JD Steakley, Wikimedia Commons)

herbs such as Scilla maritima, Nerium oleander and Adonis vernalis, as well as Lily-of-the-Valley (Convallaria majalis), by evaluating the activity of the various component glycosides: convallatoxin, cymarin, proscillaridin and scillaren. While their activity was found to be fairly equivalent, their effect on the venous system could vary greatly due to different mechanisms of action. The impact of an extract of Winter Adonis (Adonis vernalis) on venous function was stronger than that of Squill (Urginea maritima syn. Scilla maritima), Oleander (Nerium oleander) or Lily-of-the-Valley. Cymarin, which is found in Kombe (Strophanthus kombe) and Adonis vernalis, also had venous activity that was stronger than its cardioactive actions indicated (Lehmann 1984). Urginea maritima (syn. Drimia maritima). (Courtesy Javier Martin, Wikimedia Commons Project)

The 1952 Martindale Extra Pharmacopoeia provided further details regarding the therapeutic value of the Winter Adonis: Adonis vernalis slows the cardiac rate, establishes a more regular rhythm, increases diuresis, abolishes oedema and ascites, and improves the general condition. Best results are obtained in mitral stenosis, pulmonary emphysema, and cardiac insufficiency following sclerosis of the pulmonary artery. It has little use in anginal symptoms and has no effect in syphilitic aortitis. Good results were obtained in cardiac asthma, where cardiosclerosis [arteriosclerosis: hardening of the arteries of the heart] and emphysema were present. It has a more rapid action than digitalis, is not cumulative and is less toxic. The dry extract is preferable to the tincture, the recommended dose being 0.5 g six times a day, reduced in cases of sensitivity or anginal symptoms to 0.5 g three times a day, or 50 drops of 3% tincture.

The entire plant was collected just before flowering and dried. It was also regarded as having stimulant and strengthening properties. In Cyprus the herb tea has continued to be employed as a remedy for dropsy (Georgiades 1987). It is important to appreciate that the use of a herbal cardiotonic often has a valid chemical basis. An interesting study in the 1980s compared the cardiovascular potential of a number of cardiotonic

(Below) Scilla or Squill entry, from the British Pharmacopoeia, 1867.


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White Squill or Sea Onion, Urginea maritima (previously known as Scilla maritima, Urginea scilla or Drimia maritima) is an effective diuretic and cardiac tonic. There are two main cardiac glycosides in Squill bulbs (scillarins A and B), and a number of minor, but quite active, ancillary alkaloids. The herb, however, is not as potent as digitalis. Its clinical use was limited due to bioavailability issues because it was poorly absorbed and rapidly excreted. In an 1893 article T Phillips-Gibson provided an overview of the remedy, commenting: ‘Squills are used as an emetic in whooping-cough, croup, and chronic pulmonary affections, such as catarrh, asthma &c., and also as an expectorant. There are seven preparations recognised in the British Pharmacopoeia, but with the exception of the vinegar and the syrup, they require careful manipulation, and should not be attempted by any but the trained druggist or dispenser’. Syrup of Squill was ‘a favourite remedy for children suffering from croup, the dose being a small teaspoonful at intervals until vomiting is brought up, thus removing the phlegm (Thompson’s Domestic Medicine)’. This does not really sound like much of a great ‘favourite’.

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Convallaria majalis.

Lily-of-the-Valley, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

Lily-of-the-Valley (Convallaria majalis) is a familiar cottage garden herb with a long history of clinical use for heart disease. Its cardiotonic properties are similar to digitalis, albeit the effect is much less dramatic and it has particularly useful diuretic attributes. The herbalist Maude Grieve (1931) provided details for its practical use as a mild digitalis substitute, considering it to be well suited for use in valvular heart disease, cardiac debility and dropsy: ‘It slows the disturbed action of a weak irritable heart, whilst at the same time increasing its power. It is a perfectly safe remedy. No harm has been known to occur from taking it in full and frequent doses, it being preferable in this respect to Digitalis, which is apt to accumulate in the blood with poisonous results.’ Even so, the plant contains a number of cardioactive glycosides (e.g. convallarin, convallamarin, convallatoxin) that would suggest exercising care with the use of the herb.

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Hawthorn: A Premier Cardiac Tonic

Hawthorn herb is sourced from two species: Crataegus oxyacantha (syn. C. laevigata) and C. monogyna, which belong to the Rosaceae family. The latter is a widespread introduction in the southern temperate regions of Australia: New South Wales, Victoria, South Australia and Tasmania.

Hawthorn fruit is an age-old heart tonic that is currently experiencing a resurgence of popularity. For decades Hawthorn was ignored by medical research because its effects on the heart were not as dramatic as either Lily-of-the-Valley or Foxglove. The testimony of Professor Harvey Wicks Felter (1922) gives a good summary of its activity, providing details regarding its early investigation in America: The English hawthorn seems to have largely escaped the exact investigators of medicinal plants until a quite recent date … it is distinctive in occupying almost wholly a position in cardiac therapy, though recognized to some extent as a general tonic. Investigators are divided as to its activity, some claiming it only as a functional remedy, while others go so far as to claim it curative of many heart irregularities, even in the presence of an actual organic disease of that organ. Among the conditions in which Crataegus is accredited with good work are angina pectoris, endocarditis, myocarditis, and pericarditis, valvular incompetency with or without enlargement of the rings, rheumatism of the heart, dropsy depending on heart disorders, neuralgia of the heart, tachycardia, and in atheromatous conditions of the vessels … There is no doubt, however, of its value in many of the conditions mentioned, especially the functional types; and

there can be no question as to its value as a tonic to the heart muscle. It is not poisonous, has no cumulative effect and apparently from reports of a large number now using it, may be useful to control many of the symptomatic results depending on a badly functioning or tired heart. Crataegus has been suggested to rest that organ and thereby guard against arteriosclerosis.

It is important to realise that the cardiotonic effect of the remedy is progressive, making it a remedy that is best taken for a prolonged period. Over time, studies have progressively revealed the validity of many of the old therapeutic claims, and have even enhanced the herb’s reputation. The plant, which does not contain cardiac glycosides, relies on a combination of flavonoids and oligomeric procyanidins that have other mechanisms of cardiotonic activity. The herb acts by increasing coronary blood flow and facilitating the repair of heart muscle tissue. Research has shown that procyanidins (and not flavonoids such as rutin, vitexin or hyperoside) isolated from Crataegus oxyacantha and C. monogyna were also responsible for a vascular relaxant effect (Kim 2000). In addition, Hawthorn contains crataegic acids with cardiotonic attributes that act to increase coronary blood flow and reduce blood pressure. Catechins possess similar properties. Hawthorn has valuable antioxidant properties and a definite protective action against the build up of cholesterol (atheroma) in the arteries. The herb is suitable for the treatment of mild congestive heart failure, cardiac arrhythmia, coronary artery disease, angina pectoris and hypertension.5 Crataegus can have substantial benefits when used in combination therapies. It can complement the action of drugs like digitalis, providing better clinical results than if the latter was used alone. The conclusions of an extensive review of Hawthorn by Kerry Bone (1992) state: The traditional use of Crataegus for heart disease is well supported by scientific studies, although these 5 I have used this herb for many years and concur completely with its extraordinary clinical value for both humans and various species of native wildlife (CJW).


studies tend to suggest that the leaves are more active than the berries. However, as is often the case, scientific investigation has also revealed possibilities for important new actions for Crataegus. Their significance will largely be determined by a better understanding of the value of antioxidant therapy in the treatment and prevention of many common health disorders.

Clinical research continues to verify the traditional uses of this herb, suggesting particular value for the early stages of congestive cardiac failure and in the treatment of hypertension (Altern Med Rev 2010, 1998; Pittler 2008; Holubarsch 2008).

Chinese Hawthorn.

Like the European Hawthorn, Chinese Hawthorn (Crataegus pinnatifida var. major and C. cuneata) has cardiovascular tonic properties, as well as cholesterol-lowering and hypotensive activity. The stir-fried fruit has been traditionally employed as a digestive tonic for treating dyspepsia, fatty food stagnation, and stomach or abdominal distension and fullness. The raw herb (fruit) has pain-relieving properties and acts to invigorate the circulation and remove blood stasis.Thus, it has been used for treating gynaecological disorders (menorrhagia, amenorrhoea, post-partum abdominal pain), as well as angina. Additionally, it has been employed as a lactagogue (to stimulate milk secretion), a taeniacide (to expel tapeworms), and the carbonised fruit as an astringent antidysenteric agent (Lou 1987; Yeung 1985; Bensky & Gamble 1986).

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The Medicinal Rose

Roses have been among the most prized and familiar plants in the cottage garden.6 It may, however, come as a surprise to learn that since ancient times Rose petals have been accorded great respect as a medicine, as well as a colouring agent and a fragrant additive. Numerous species have medicinal properties – a few of which earned official recognition in the various pharmacopoeias. They include the China Rose (Rosa chinensis), Apothecary’s Rose (R. gallica), Cabbage Rose (R. centifolia), Damask Rose (R. damascena), Sweetbriar or Eglantine (R. eglanteria) and the Chestnut Rose (R. roxburghii). The Damask Rose provides a good illustration of the validation of a traditional remedy by modern science. In general, Rose oil has antibacterial and antioxidant properties that are particularly well suited for use in cosmetics and skin formulations. Investigations of the antimicrobial efficacy of Rosa damascena absolute and essential oil (which contain high levels of phenolics7) showed strong antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Chromobacterium violaceum and Erwinia carotovora. This was linked to the phenyl ethyl alcohol content (PEA 72–78%) (Ulusoy 2009). The oil’s substantial antibacterial properties against Propionibacterium acnes also support its use in acne treatments (Zu 2010).8 However the hydrosol preparation, which had significantly lower levels of phenyl ethyl alcohol than the absolute or essential oil, showed no antimicrobial activity (Ulusoy 2009).9

6 Species naturalised in Australia include R. bracteata, R. canina, R. chinensis, Rosa x damascena, R. gallica, R. indica, R. laevigata, R. luciae, R. multiflora, R. odorata, R. roxburghii and R. rubiginosa. 7 The total phenolic contents of the absolute was extremely high (2134 gallic acid equivalent [GAE] per mg/L), although the level in the essential oil was also quite good (849 GAE/mg/L). In comparison, that of hydrosol was very low (5 GAE/mg/L) (Ulusoy 2009). 8 Cinnamon, Thyme and Lavender oils have similar antibacterial potential (Zu 2010). 9 Rose hydrosol: PEA (24%) – as well as geraniol (31%), citronellol (29.5%) and nerol (16%). PEA, which has a rose-like aroma, has been utilised as a fragrance ingredient in cosmetic products and culinary items such as beer, wine, olive oil, grapes, tea, apple juice and even coffee (Ulusoy 2009).

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The wild Damask Rose (Rosa damascena), originally from the Balkans and Asia Minor, is the source of Attar of Roses – the Rose oil typically used for perfumes and as a flavouring. It is also reputed to have rejuvenation properties. Traditionally, Attar of Roses was inhaled to calm the nerves and promote sleep – as well as being useful for menstrual distress. Damask Rose essential oil is primarily composed of hexatriacontane (24.6%), geraniol (15.05%), nonadecene (18.56%) and tricosane (16.68%) – as well as smaller amounts of linalool (3.8%), nerol (3.05%) and pentacosane (3.37%) (Yassa 2009). Other analyses indicate the composition can vary somewhat: citronellol (15.9–35.3%), geraniol (8.3–30.2%), nonadecane [sic] (4.5–16.0%), heneicosane (2.6–7.9%), linalool (0.7–2.8%) and nerol (4.0–9.6%) (Verma 2011). (Image courtesy Kurt Stüber, CC-by-SA 3.0) Rose preparations, from the British Pharmacopoeia, 1867.

Rosa gallica var. officinalis.

Maude Grieve (1931) recorded the following interesting details regarding the official Apothecary’s Rose:

Confection of Red Rose, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

The British Pharmacopoeia directs that Red Rose petals are to be obtained only from R. gallica, of which, however,

there are many variations, in fact there are practically no pure R. gallica now to be had, only hybrids, so that

FLOWERS OF THE MATERIA MEDICA the exact requirements of the British Pharmacopoeia are difficult to follow. Those used in medicine and generally appearing in commerce are actually any scented roses of a deep red colour, or when dried of a deep rose tint. The main point is that the petals suitable for medicinal purposes must yield a deep rose-coloured and somewhat astringent and fragrant infusion when boiling water is poured upon them.

In particular, Rose water ointment has long been highly regarded as a soothing agent for skin problems (rough, dry or chapped skin). A tincture made from Rose petals provided an anti-haemorrhagic agent and stomachic (tonic for gastric function). Rose oil was particularly valued for its soothing effects on the nerves and was used as a remedy for insomnia and depression.10 It takes a staggering number of roses to make an ounce of Rose oil – which, incidentally, is not the anticipated bright red hue but assumes an orange-green colour. Other Rose-based preparations that have been utilised medicinally include Rose-petal tea, Rose honey and Rose vinegar.

The Aromatic Rose

The production of Rose essential oil is a labourintensive process. The freshly opened flowers are hand-harvested before dawn to avoid the drying effects of the sun on the blooms – an important consideration that can significantly affect the oil yield. The Damask Rose is the Pink flowered Rose. main source of Attar of Roses (Rose absolute) – a high-priced concentrated fragrance that is extracted by a solvent or supercritical carbon dioxide extraction. The yield is 5–10 times that obtained by stem distillation, a process used to produce Rose Otto (Ulusoy 2009; Widrlechner 1981). Rose absolute, which is favoured by the perfumery 10 Many essential oils, including that of the rose, have anxiolytic attributes that are associated with a relaxant effect (Hongratanaworakit 2009; Setzer 2009). Experimentally, rose oil injections were noted to have an anti-seizure effect, and investigations have subsequently focused on the neuroprotective potential of various Rose-derived extracts and oils (Awale 2011; Jung Choi 2009; Ramezani 2008).

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industry, primarily contains phenylethyl alcohol (72–78%), with lower levels of citronellol (10–11%) and nerol (3–4%) – as well as nonadecane (4%) or geraniol (5.6%). The absolute also contains β-carotene (422 ppm) and tocopherol (ɑ-tocopherol 2397 ppm; y-tocopherol 422 ppm) at levels higher than is found in the essential oil or hydrosol (Ulusoy 2009). There are some interesting accounts of early Australian attempts at the extraction of Rose perfumes. A report by Mr BG Hardy (1894) eloquently illustrates the frust-ration associated with problematic weather conditions and difficulties in supply: I must state a matter for considerable regret, inasmuch as on my arrival [at the nursery] the weather had a promising appearance for a continuance of fine weather, but immediately after I had commenced work, an unfavourable change took place, and heavy rains set in. This, unfortunately, continued more or less for thirtyfive days, with only two exceptions, and during that period over 14 inches of rain fell. It is hardly necessary for me to point out how detrimental this would be to the retention of the perfume by the flowers until I could work them, and in almost every case, all through the work, I had to express the water from the blooms before I could lay them down, thereby losing a very valuable portion of their odour. White rosebud.

He paints a vivid picture of the challenges encountered: Beyond this, I was, throughout the work, at very considerable disadvantage from insufficient space and the primitive nature of the building placed at my disposal for operating in, and the irregular and curtailed supply for flowers. On the latter point, I may explain that I never commenced work on a flower without first inquiring if there would be a sufficient supply of bloom available at regular intervals to carry the experiment to completion, but I frequently found,

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary when at actual work, that from some cause or other I could not obtain a recharge for sometimes nearly a week instead of daily, and at other times the bloom allowed me totally ceased after, perhaps, one, two or three changes, in place of at least a dozen required

While a number of oil samples were not as complete as he had wished, he had certainly demonstrated the viability of the venture: ‘Nevertheless, in every case they are satisfactory in quality and strength, as far as the opportunity would allow, and demonstrate the facts that under more favourable circumstances, articles of high quality may be produced and carried forward to commercial success’. Perfumes from Bouvardia, Tuberose, White and Red Roses, Carnations, Phlox and Spikehead were all of a valuable quality. He also considered that: ‘I would express my opinion that … it would be found that many of our native plant might profitably be brought into cultivation for perfumery purposes, and give odours of a special value to the trade for manufacturing new preparations, and without doubt the very fact of offering new specialities in Australian perfumes would operate beneficially in the sale of all our other perfume products.’

Remedies from Rosehips

Rosehips.

Confection of Dog Rose hips, from Phillips’ Translation of the Pharmacopoeia Londonensis, 184

Wildflower perfume and Boronia hand and body lotion. Australian wildflowers have a wonderful evocative scent of the native bush. Of these, Boronia, sourced from Boronia megastigma, is a premier native wildflower perfume of international fame.11 (Images courtesy House of Sharday, Australia)

Citrus fruits such as lemons and oranges have long been valued for their vitamin C content, although there are other plants that qualify as superior resources, particularly rosehips (Rosebush fruits). These can be easily sourced from the various common species, including the Dog Rose (Rosa canina), the Field Rose (R. arvensis), the Downy-leaved Dog Rose (R. mollis) and the Potato Rose (R. rugosa). In general, the fruits contain malic and citric acids, sugars, essential fatty acids, fat-soluble vitamins (β-carotene, lycopene, tocopherol), flavonoids, various minerals12, a trace of tannin, and ascorbic acid 0.4–1.0 per cent. An analysis 11 See Volume 1 for further details. 12 Rose fruit, flesh and seeds can contain quite good levels of phosphorus, potassium, calcium, magnesium and iron. Sodium levels are low. Manganese, zinc, copper and boron may also be present (Kazaz 2009).


of Rosa micrantha found ascorbic acid was abundant in all parts of the rose, albeit richest in the ripening hips (944 mg/100 g). This was comparable to that of other species (726–943 mg/100 g)13: R. canina, R. dumalis, R. dumalis subsp. boissieri, R. dumalis subsp. antalyensis, R. micrantha, R. pisiformis, R. pulverulenta, R. rubiginosa and R. villosa. To put this in perspective, the vitamin C content of R. rubiginosa at 400 mg/100 g was 10-fold higher than orange juice, and 15 times that found in citrus fruits. The dried fruit, unfortunately, loses the majority (95%) of its vitamin C content (Guimaraes 2010; Moure 2001; Hornero-Mendez & Minguez-Mosquera 2000). The British Pharmaceutical Codex of 1949 noted: Rose fruit is a rich natural source of ascorbic acid, and contains from three to four times as much of this constituent as black currant, and about twenty times as much as orange juice. A palatable syrup suitable for infants and children is prepared from the fresh fruit and has a standardised ascorbic acid content of 2 milligrams per millilitre. The daily prophylactic dose of this syrup for a child in 12.5 millilitres (190 minims), but as a dietary supplement it is usual to give about 4 to 8 millilitres (60 to 120 minims). Rose fruit is also employed in the preparation of a confection which is occasionally used as pill excipient.

Additionally, Rosehips could be stored frozen until required for making syrup. In folk medicine traditions Rosa canina fruit (decoction or syrup) was employed in an interesting range of disorders – malaria, haemorrhoids, hepatitis, stomach-ache and bronchitis. The fruit of Rosa sempervirens was used similarly in Turkey (Tuzlaci & Aymaz 2001). Doubtless the support that vitamin C provides the immune system would play an important part in the therapeutic efficacy of rosehip extracts – which possess significant antioxidant properties (Poblete 2009; Buricova & Reblova 2008; Speisky 2006). Carotenoids are another important component of rosehips that are responsible for the 13 Another review gives a much greater variation in vitamin C levels, ranging from 106–2712 mg/100 g. Levels in the fruit flesh of R. canina and R. damascena were found to be the highest (2200 and 546 mg/100 g respectively), substantially more than was present in the seeds (306 and 145 mg/100 g respectively). ɑ-tocopherol (ug/g) was higher in R. canina fruit (34 ug) than the fruit flesh (21.6 ug) and lowest in the seed (8 ug) – which was substantially higher than for R. damascena (7 ug fruit, 5.35 ug flesh and 5.25 ug seed). β-carotene levels did not alter significantly in the different plant parts of R. damascena (2.95–3.7 ug) and, although levels in R. canina were similar (2.6-3–25 ug) in fruit and fruit flesh, that of the seed of was quite low (0.18 ug) (Kazaz 2009).

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intense colouring of the hip (which can vary from rich yellow to a bright red) and rose petals. Rosa micrantha contained high levels of β-carotene (46–62 mg/100 g) and lycopene (17–59 mg/g) in the hips (overripe and ripening fruit) and flower petals. The content was similar in Spanish samples of Rosa rubiginosa hips (49.7 mg and 39.2 mg, respectively). A range of other carotenoids are also present, notably rubixanthin, gazaniaxanthin, β-cryptoxanthin, and zeaxanthin (Hornero-Mendez & Minguez-Mosquera 2000).

Rosa roxburghii. (Courtesy Salvor Gissurardottir)

Popular Rosehip resources also include the Cherokee Rose (R. laevigata), the Multiflora or English ‘Tea Rose’ (R. multiflora), and the Chestnut Rose (R. roxburghii). The latter is a commercial source of rosehip powder from China. The vitamin C content is 5–7 per cent (794–2391 mg/100 g fresh fruit) and vitamin P (flavonoid content: 5981– 12895 mg/100 g) (Nantong Sihai Plant Extracts Co. Ltd, www.made-in-china.com). Rosa roxburghii is considered to have useful antioxidant, circulatory and cardiovascular tonic properties. Experimentally, extracts demonstrated anti-arteriosclerosis activity and benefits for cholesterol levels that support its use for cardiovascular disorders. The herb is also considered to have rejuvenation, immune supportive and anticancer effects (Burke 2005; van Rensburg 2005; Zhang 2001; Ma 1997; Hu 1994). Other species appear to possess similar activity. Rosa damascena extracts (buds and component flavonoids) possess cardioactive properties that support its use as a cardiotonic14 (Kwon 2010; Yassa 2009) – and R. davurica (fruit extracts) demonstrated anti-ischaemic properties with cardioprotective potential (Jiao 2004). 14 A number of terpenes (ɑ-pinene, β-pinene, citronellol, linalool) that are found in essential oils possess hypotensive activity (Menezes 2010).

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Rosehip Seed Oil

Rosehip – cut fruit with seeds.

An evaluation of essential fatty acids in the seeds of R. damascena and R. canina have confirmed a high unsaturated fatty acid content, characterised by moderate levels of oleic acid (24 and 22%, respectively) and ɑ-linolenic acid (15 and 20%, respectively), with much higher levels of linoleic acid (54 and 49%, respectively). Overall, low levels of palmitic (5%) and stearic acids (2–3%) were present. This was comparable with other studies of these oil components15 (Kazaz 2009). Rosehip oil can be of benefit in numerous irritable skin disorders, including eczema, skin ulcers, neurodermatitis (a highly discomforting inflammatory skin disorder associated with chronic itching and scratching) and cheilitis (inflammation of the lip). The soothing antiinflammatory effects can be enhanced by combination with fat-soluble vitamins. However, those individuals who are susceptible to contact allergy problems with rosehip and rose oils should avoid these products (Chrubasik 2008; Shabykin & Godorazhi 1967).

Sukin Rosehip Oil. (Courtesy Sukin Organics Pty Ltd, Australia)

Rosehips were traditionally de-seeded, with the best preparations utilising the fresh hip. The seeds within, which are covered by a hairy skin, would therefore have been discarded. However, times change, and the seeds are now considered to be an excellent oil resource with a high essential fatty acid content (oleic, linolenic and linoleic fatty acids) of value to the cosmetic industry. These unsaturated fatty acids can be obtained from numerous species: R. canina, R. dumalis subsp. boissieri, R. dumalis subsp. antalysensis, R. micrantha, R. pisiformis, R. pulverulenta, R. rubiginosa, R. villosa. In addition, palmitic acid was identified as the main fatty acid in the petals and fertilised flowers of R. micrantha (Guimaraes 2010).

The Mosqueta Rose (Rosa rubiginosa, syn. R. eglanteria) is native to South America and is a rich rosehip seed oil resource. It has been traditionally utilised as a healing agent that was particularly valued for open wounds and ulceration (Santos 2009; Moreno-Gimenez 1990). (Image courtesy Adrian Barabino) 15 Oleic (16–22%), lineolic (36–55%), ɑ-linolenic (20–26.5%), palmitic (3.6–8%), and stearic (2–3%) acids (Kazaz 2009).


A number of Rose species possess particularly good anti-inflammatory and analgesic properties – they include the Persian Rose, Rosa damascena (hydroalcoholic extracts of dried petals, but not the petal oil), R. canina (rosehip extracts), R. multiflora (rosehip extracts), and R. rugosa (root extracts). The latter contains tormentic acid (a triterpene saponin) with anti-inflammatory activity16 (An 2011; Lattanzio 2011; Hajhashemi 2010; Yassa 2009; Zhang 2008; Jung 2005). Research over the last few decades has shown valuable therapeutic applications for the rosehip. Rosa canina hip powder has good potential for clinical use as an anti-inflammatory and analgesic in osteoarthritis, rheumatoid arthritis and low back pain (Olsen 2011; Willich 2010; Christensen 2008; Chrubasik 2008) – although there is some controversy with regard to its efficacy (Kirkeskov 2011). Rosehip extracts contain triterpenes with antimicrobial, immunomodulatory and anti-inflammatory properties – oleanolic, betulinic and ursolic acids, with a synergistic action that contributes to their efficacy (Saaby 2010). Certainly, these studies suggest that Rose-based additives could have more extensive applications than is currently appreciated by the pharmaceutical and cosmetic industries – as well as culinary uses as antioxidant and antimicrobial flavouring agents (Egea 2010; Guimaraes 2010; Yassa 2009). Rosa davurica is a northern Asian species (China, Mongolia, Korea, Siberia) that has been utilised as an anti-inflammatory remedy and to treat skin growths. Dried leaf extracts possess analgesic and antiinflammatory properties – as well as anti-angiogenic (preventing tumour metastasis) and antioxidant effects that could help explain its use for tumorous growths (Jung 2011). Rosehip powder (from Rosa canina) has shown some interesting anticancer and radioprotective properties. It had an inhibitory effect on melanoma (skin cancer) cells, as well as a supportive (synergistic) effect when combined with the anticancer drug 5-fluorouracil (Adrucil) in endometrial cancer cell studies. Flavonoids (proanthocyanidins17) from rosehip extracts were of particular interest as potent inhibitors of melanin biosynthesis (Dai 2011; Fujii

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2011, 2009; Akhmadieva 1993). Hydrolysable tannins are among the main phytochemicals present in rose extracts. Gallic acid (and derivatives) were identified among the main antioxidant, anti-inflammatory, antimutagenic and anticancer components of Rosa rugosa extracts. Polysaccharides with antioxidant activity were also present (Choi 2009; Ng 2004). The potent antioxidant properties of Rosa canina (rosehips) were likewise linked to its phenolic components18 (Kilicgun & Altmer 2010) – as were benefits for lipid metabolism from R. centifolia extracts (petal extracts and rose ellagitannins)19 (Kondo 2011).

Multipurpose Rose Remedies

Numerous studies have shown antibacterial properties (including activity against dental bacteria) for various rose products – which certainly support their healing reputation. Indeed, extracts prepared from Damask Rose receptacles have demonstrated a broad range of antimicrobial activity against Candida albicans,

Scanning electron micrograph showing Salmonella typhimurium (red) invading cultured human cells. Salmonella are gram-negative pathogens that are responsible for food poisoning and food spoilage. Extracts of the Damask Rose (receptacles) and the Multiflora Rose (Rosa multiflora, flower and leaf ) possess good activity against Salmonella typhimurium (Frey & Meyers 2010; Talib & Mahasneh 2010). (Image courtesy Rocky Mountain Laboratories, NIAID)

16 Rosa rugosa (white petal extracts) has also demonstrated anti-allergic, antioxidant and anti-inflammatory activity (Jeon 2009; Park 2009).

18 A study of Rosa micrantha linked antioxidant activity with the level of phenolic components. The highest levels (mg/GAE/g ext) was found in the fertilised flowers (527 mg), slightly less in the petals (424 mg), and lower levels in over-ripe (304 mg), ripening (188 mg) and unripe (142 mg) hips (Guimaraes 2010).

17 Quercetin demonstrated a particularly potent activity for the inhibition of melanin biosynthesis, however the level present in rosehip extracts was low (Fujii 2011).

19 Some studies suggest rosehip seed extracts have anticholesterol and metabolic regulating activity with potential to assist weight control (Chrubasik 2008).

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methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhimurium and Bacillus cereus (Talib & Mahasneh 2010). The antibacterial properties of Rose extracts extend to dental pathogens and it has been employed in treatments for aphthous stomatitis (canker sore), which is an extremely difficult condition to treat. This is a form of mucous membrane inflammation of the mouth that is often associated with recurrent painful ulceration. Clinically, a mouthwash containing Rosa damascena extract gave good results (Hoseinpour 2011; Shokouhinejad 2010).

Antiviral Tannins

Wild Rose, Rosa canina, a Bach Flower Remedy. This remedy is to help with a sense of apathy and disinterest in life – with an accompanying feeling of sadness and depression. (Image courtesy Martin & Pleasance, Port Melbourne)

Rosa species have been traditionally utilised as antidiarrhoeal remedies – an activity that has been linked to their tannin (polyphenol) components. They include Rosa canina, R. centifolia, R. sempervirens, R. eglanteria, R. laevigata and R. rugosa (Kamijo 2008; Tuzlaci & Aymaz 2001; Lust 1974). Indeed, Rosa canina (leaf extracts) demonstrated very good antidiarrhoeal activity in animal studies (Mandade 2011). This activity has been supported by investigations showing diverse antimicrobial properties for the genus. Interestingly, Rosa rugosa (flower petal) extracts showed excellent antibacterial activity against various intestinal bacteria (Bacteroides vulgatus, Escherichia coli, Staphylococcus aureus and Bacillus cereus). This was linked to the hydrolysable tannin components, notably rugosins and tellimagrandins. Tellimagrandin I was of special interest due to an antibacterial drugpotentiation (synergistic activity) with prospects for clinical use – for example, in combination with tetracycline or oxacillin to enhance the efficacy of these antibiotics (Tamura 2010; Kamijo 2008; Shiota 2004, 2000).

Tellimagrandins and similar phenolics (ellagitannins) are found in Clove (Syzygium aromaticum), Geum (Geum japonicum) (Kurokawa 1998) – and some Eucalyptus species – including E. globulus, a massive specimen of which is shown here, and E. nitens (Barry 2001; Hou 2000). (Image courtesy Kim and Forest Starr, Hawaii)

Antiviral studies of the Rosaceae have shown that Rosa rugosa and Prunus sargentii have experimental HIV-inhibitory activity. The triterpenoid rosamultin was identified as the most active component of Rose root extracts (Park 2005). Tannins also appear to have significant influence on the antiviral properties of various plant extracts – although this activity is likely to be due to a natural combination of the component phenolics rather than an individual component. Indeed, tellimagrandin I, eugeniin and casuarictin from Rosa rugosa flower extract have demonstrated antiviral potential against the hepatitis C virus (Tamura 2010). Tellimagrandin II has shown anti-herpes virus properties – although studies have also shown that extracts of Geum japonicum and Rhus javanica, which contain eugeniin as a major anti-herpes component, possessed activity against the cold sore virus (Herpes


simplex) (Kurokawa 1998 & 1995). Both species show immunological activity with a significant cytomegalovirus inhibitory effect. Terminalia chebula and Syzygium aromaticum were found to be similarly effective (Shiraki 1998, Yukawa 1996). Geum japonicum has been used in traditional medicine as an astringent and diuretic agent. Extracts of the herb have shown anticancer and antiviral (anti-AIDS) potential (Heo 2008;

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Rosehip powder, in combination with probiotic bacteria (Lactobacillus plantarum) has interesting potential for regulating gastrointestinal function (decreased flatulence, increased stool volume, softer stools) – with an extract of rosehip seeds also showing anti-ulcer activity. A rosehip and lactobacillus combination demonstrated experimental benefits for tissue recovery after colonic injury stress, which led to suggestions for its use as a pre-treatment in surgical procedures – for example, organ transplants, colon or vascular surgery (Chrubasik 2008; Hakansson 2006). A couple of other intriguing studies have shown Rosa canina extracts could act against the formation of calcium oxalate stones, which indicates that it may have potential for the prevention and treatment of urolithiasis (kidney stones) (Tayefi-Nasrabadi 2011; Chrubasik 2008). This certainly deserves further investigation.

Geum japonicum. (Courtesy Judy Monkey, flickr)

Kageyama 1996). It also contains various triterpenes with experimental anti-HIV activity, such as maslinic acid and ursolic acid (Xu 1996). Tannins with anticoagulant properties have also been isolated (Dong 1998). Herbal extracts have shown significant antioxidant and radical scavenging properties that were linked to trihydroxybenzaldehyde (3,4,5-THBA)20 – 105 mg/kg in leaf; 240 mg/kg in stem (Kim 2006). Recent investigations have specifically focused on regenerative effects of the herb and an active component (cardiogenin) on the myocardium – suggesting the remedy has extensive potential for facilitating recovery from heart attack (Cheng 2009; Li 2006). Two species of Geum are found in Australia: G. talbotianum (Tasmania) and G. urbanum (NSW and Victoria) – albeit their medicinal potential is unknown. 20 Synonym: pyrogallol-5-carboxaldehyde.

In Chinese medicine, Rosa rugosa leaf tea has long been recommended as a febrifuge. The flowers, however, had a more extensive medicinal reputation: promotion of blood circulation, for bleeding problems (haematemesis, haemoptysis), digestive disorders (dyspepsia, stomach-ache) and the regulation of spleen and liver function (hepatitis). The flower could also be applied locally to treat infections such as an abscess or a breast boil in nursing mothers (Duke & Ayensu 1985). Furthermore, the root has been traditionally employed as a cough remedy and for the treatment of diabetes mellitus (Jeon 2009). Rosa rugosa seed oil is high in linoleic and linolenic acids (44.5% and 32%, respectively), as well as containing a moderate amount of palmitic acid (17.6%) (Duke & Ayensu 1985).

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The Cherokee Rose

Cherokee Rose, Rosa laevigata. (Courtesy Bron Praslicka, flickr)

Rosa laevigata (fruit, roots and leaves) has traditionally been utilised as an astringent, carminative, antimicrobial, tonic and healing remedy for innumerable conditions: urinary tract disorders (enuresis, polyuria, chronic infections), gynaecological problems (dysmenorrhoea, menorrhagia, pelvic inflammation, cervicitis), gastrointestinal distress (dysentery, diarrhoea, enteritis), male sexual problems (spermatorrhoea, premature ejaculation) and respiratory distress (cough, bronchitis). The leaves have been highly valued as a vulnerary (healing agent) (He 2009; Duke & Ayensu 1985). Triterpenes were isolated from leaf and root extracts with anti-inflammatory and antifungal (anti-Candida) properties (Zeng 2011; Yuan 2008). Root extracts have also shown good hepatoprotective activity (He 2009). Interestingly, the plant contains an antioxidant brown pigment that may have potential uses as a food additive (Xiao 2011) The Chinese Tea Rose (Rosa chinensis) is another of the red roses with a substantial medicinal reputation. In Belize it provided an astringent, cooling remedy for feverish conditions and childhood diarrhoea. A tonic infusion was prepared from a single red rose, with nine leaves, steeped in a cup of boiling water for 15 minutes. A stronger infusion employed three red roses with a handful of leaves (similarly prepared) for adult diarrhoea or haemorrhagic problems. Flower extracts possess broad spectrum antifungal and anti-candidal activity, as well

Rosa chinensis.

as antibacterial properties (Arvigo & Balick 1993). In Chinese traditions the fruit was applied locally to heal ulcers, wounds and sprains. The decoction (leaf, fruit, root) was taken as an antirheumatic and anti-arthritic remedy, to alleviate haematuria (blood in the urine), as an antitussive for cough or applied locally for skin infections (boils). The flower buds were recommended for dysmenorrhoea, circulatory problems and stomach pain (Duke & Ayensu 1985). The analgesic, antimicrobial and anti-inflammatory activities of other Rosa species support similar medicinal reputations. Rosa damascena (extracts and essential oil) has bronchodilatory and antitussive effects useful for cough relief – with some extracts exhibiting activity comparable to the anti-asthmatic drug theophylline (Rakhshandah 2010). Rosa centifolia flower extracts have antitussive properties comparable to codeine phosphate, which support the herb’s traditional use for respiratory distress. The essential oil was reported to have gastrointestinal relaxant and bronchodilatory effects. In addition, the flowers have been utilised as an antibacterial remedy (including the treatment of conjunctivitis) and as a remedy for diabetes (Anand Sankar 2011). Interestingly, recent studies support the antidiabetic potential of Rosehip extracts and Rosa damascena flower extracts (Andersson 2011; Gholamhoseinian 2009). Trans-tiliroside from rosehip and seed extracts was found to have a blood glucose-lowering effect, as well as beneficial effects on lipid metabolism (Chrubasik 2008). The Provence or Cabbage Rose (Rosa centifolia) is a hybrid rose from eastern Caucasia that is one of the oldest cultivated roses and the source of Rose

FLOWERS OF THE MATERIA MEDICA (Left) Rose water elixir. (Courtesy D McCarthy, www.elixirsoflife.co.uk)

(Below) Rosa centifolia foliacea, by the French botanical artist Pierre-Joseph Redouté (1759– 1840).

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into a polyherbal formulation (V-Gel) that has a good clinical reputation for the treatment of vaginal and cervical inflammation. It is suitable for use in chronic conditions and in the post-partum period (following childbirth). The gel is composed of a number of herbs with antimicrobial, disinfectant, astringent, anti-inflammatory and healing properties: Berberis aristata, Neem (Azadirachta indica), Vitex negundo, Cardamomum (Elettaria cardamomum), Henna (Lawsonia inermis), Parmelia perlata (lichen), Cedrus deodara, Tagetes erecta, Boerhaavia diffusa, Nelumbo nucifera and Anethum sowa (Ranjana & Misra 2001). V-Gel was shown to be effective against the causative agents for trichomonal vaginitis and vaginal candidiasis, as well as some non-specific organisms (e.g. Gonococcus vaginalis) (Vermani & Garg 2002).

Rosa multiflora. (Courtesy Ronnie J Ortiz)

water. The tea has aperient properties – as well as being used as a styptic (infusion, powder or as a tincture) for treating haemorrhage (Lust 1974). The soothing, anti-inflammatory and antimicrobial properties of Rosa centifolia has seen it incorporated

The Multiflora Rose (Rosa multiflora) has an equally potent antimicrobial reputation. The leaves were poulticed on sores, while the fruit and root were useful for ‘foul injuries’, sores, sprains and wounds – which suggests exceptionally good antibacterial and healing properties. Studies have confirmed that extracts of the leaf, stems and flowers were bactericidal (Duke & Ayensu 1985). In Chinese traditions this rose is highly regarded as an astringent, carminative, diuretic and wound-healing remedy. Similar to various other species, the root has been utilised for rheumatoid arthritis, skin disorders and scabies infections (Duke & Ayensu 1985). Root extracts, which contain condensed tannins, have shown immunomodulatory and anti-inflammatory properties with potential for the treatment of allergic

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and inflammatory skin disorders such as dermatitis and psoriasis. The rosehip extract also possessed antiinflammatory and analgesic potential (Park 2011, 2010; Zhang 2008). In addition, the fruit has been utilised as an antidote for fish poisoning (Duke & Ayensu 1985).

Rosa multiflora fruit are rich in carotene (81 mg/100 g) and vitamin C, and contain multiflorin (Duke & Ayensu 1985). The latter is of interest as multiflorin A (a kaempferol glycoside), isolated from peach leaf extracts, has shown anti-hyperglycaemic properties via inhibition of glucose absorption in the intestine. Prior studies have also suggested that multiflorins A and B have purgative potential (Shirosaki 2012). In addition, the UVB protective effects of peach flower extracts were linked to the presence of multiflorin B (Kim 2002). (Image courtesy Susan Sweeney)

Fragrance and Flavourings in Pharmacy

An important, often underestimated, aspect of the traditional medicine chest is a diverse range of flavouring components, the majority of which have been in use for centuries. Innumerable oils that possess powerful aromatic flavouring qualities are utilised as carminative agents, to soothe gastric distress. Many essential oils are also potent antimicrobial candidates and there has been an enormous amount of research in recent years focusing on this aspect of their medicinal potential. The early chemists in the Australian colony took a keen interest in aromatics and flavourings, although a lack of chemical and entrepreneurial expertise appears to have hampered their commercial success. Joseph Maiden lamented:

Official recommendations for the use of Orange peel: syrup, tincture and wine preparations from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899.

Lemon continues to be an important flavouring for medicinal and culinary use. It has additional value as a respected vitamin C resource. (Courtesy Dr Reckeweg & Co., Bensheim, Germany)


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Official recommendations for the use of Lemon peel: oil syrup and tincture preparations from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899. At present it unfortunately is frequently the case that large quantities of Citrus fruits rot on the ground, or are otherwise underutilised, simply because it does not pay to take them to market. In Southern France (Sicily and South Italy in particular), oils are obtained from the rinds of the fruit thus left on the growers’ hands. I quite think that the utilisation of surplus and inferior fruit in this way should be enquired into in our own Colony … Orange oil is also made from the scarcely ripe fruits of both sweet and bitter oranges. It is chiefly used in perfumery, and in the fabrication of liqueurs. Oil of lemons should certainly be made in Australia to satisfy all local requirements, and to provide a quantity for export. It is used largely for flavouring (in cookery, aerated waters, &c), perfumery &c. Some is already made in the Australian colonies, if the advertisement of a certain aerated-waters firm is to be taken literally … While dealing with rinds, it would be borne in mind that the peel of the bitter orange is very extensively used in medicine, the Colonies alone

Tincture of Lemon: prepared by an Australian manufacturer – Taylors Elliotts & Australian Drug Pty Ltd, Brisbane. consuming many tons per annum, but the supplies from local sources are small and uncertain. Orangeflower water and oil of Neroli (the latter being the essential oil which perfumes the former), are prepared by subjecting the flowers of both bitter and sweet orange to distillation. These products are valuable, and that they can be remuneratively manufactured in this Colony I have no doubt (Maiden 1892).

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Since this time the market for essential oils in Australia has boomed – with a remarkable range of high quality products sourced from both traditional and innovative native resources.

Orange tincture. (Courtesy The Apothecary, Cairns) (Right) Orange oil. (Courtesy The Apothecary, Cairns)

Citrus aurantium, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. J M’Gregor-Robertson, in The Household Physician (1908), commented that: ‘The [rind of the] Bitter or Seville orange … is rich in flavouring oil, and is largely used for flavouring, and for the extraction of tincture, to be employed as an aromatic tonic. The flavour of the liqueur curaçao is due to the bitter orange. From the flower of this variety, also, the finest orange flower water is distilled. From orange-flowers another oil is obtained – the oil of neroli’ (M’Gregor-Robertson 1908).

Table 1.1 Overview of the Main Essential Oil-yielding Herbs and Spices with Flavouring Qualities that are Utilised in Pharmacy (Note: This table does not discuss the aromatherapy uses of these oils.) Flavouring component (official source) Aniseed (Pimpinella anisum) Star Anise (Illicium verum)

Oil composition (Evans 2002) Medicinal qualities and notes (British Pharmaceutical Codex: BPC 1968; BPC 1934) Anise oil: Aniseed and Star Anise have very similar chemical constituents, primarily anethole 80–90%. Both are used for the production of anise oil (Evans 2002). Other components: chavicol methyl ether, p-methoxyphenylacetone, safrole. Attributes: carminative, mild expectorant Uses: • Anise oil is used in mixtures and cough lozenges, often in combination with liquorice (BPC 1968). • Aromatic, carminative. Used internally as galactagogue, to relieve flatulence; flavouring to mask unpleasant odour of remedies; externally as liniment and ointment in painful conditions, and in pediculosis (Merck Index 1940).

FLOWERS OF THE MATERIA MEDICA Camphor (Cinnamomum camphora)

Caraway (Carum carvi)

Cardamomum (Elettaria cardamomum var. misicula)

Cinnamon, Cassia bark (Cinnamomum zeylanicum)

Clove (Syzygium aromaticum)

Coriander (Coriandrum sativum)

Dill (Antheum graveolens)

Camphor oil: camphor, safrole, borneol, heliotropin, vanillin, terpineol, plus sesquiterpene alcohols (Evans 2002). Attributes: carminative; rubefacient Uses: • Mild antiseptic, carminative; rectified camphor oil (a by-product of camphor manufacture) has been employed as a rubefacient and mild counter-irritant to rheumatic and inflamed joints. It may be applied undiluted or mixed with olive oil or methyl salicylate. Also used as parasiticide (BPC 1934). • Stimulant, antiseptic, rubefacient, parasiticide; external use with olive oil as liniment for rheumatism, neuralgia, myalgia, lumbago, bruises, sprains; for parasitic skin diseases (Merck Index 1940). Note: Camphor oil is separated into four distinct essential oil types by fractional distillation. White camphor oil does not contain safrole and is the type normally sold as ‘camphor oil’ for use in aromatherapy. Toxicological concerns regarding safrole have limited the general use of the other forms of camphor oil (Tisserand & Balacs 1995). Note: See Volume 1 for a discussion on safrole toxicology. Caraway oil: primarily carvone and limonene, small amounts dihydrocarvone, carveol, dihydrocarveol (Evans 2002). Attributes: carminative and antispasmodic Uses: • Aromatic carminative; a component of purgative pills to allay the tendency to gripe; administered on sugar to relieve flatulent colic (BPC 1934). • Caraway Water (Aqua Cari) used in treatment of flatulence and is a suitable vehicle for children’s medicines (BPC 1968; BPC 1934). Cardamomum oil: primary components are terpinyl acetate, cineole. Cardamom tincture (prepared from seeds): this is the main form used in pharmacy Attributes: carminative properties Use: • Compound Cardamomum tincture: cardamom seed 1.4%, Caraway, cinnamon, cochineal, alcohol (60%) (BPC 1968). Oil of Cinnamon: cinnamic aldehyde (60–75%); phenols mainly eugenol (4-10%), plus small amounts pinene, phellandrene, caryophyllene, etc (Evans 2002). Attributes: mild astringent, carminative, powerful germicide (Evans 2002). Uses: • In capsules, on sugar or as Spiritus Cinnamomi for common colds and influenza. Oil inhaled for phthisis and used as a spray in catarrh. Also employed in preparation of lozenges and pastilles (BPC 1934). • Aromatic carminative for use internally to treat colic (Merck Index 1940). Clove oil: eugenol (84–95%, incl. 3% acetyleugenol), ɑ- & β-caryophyllenes (at least 28 compounds reported) (Evans 2002). Attributes: carminative; useful preservative; external use as liniment with irritant, rubefacient, slight analgesic properties (BPC 1968). Uses: • Clove oil employed in dentistry; local analgesic effect, do not use excessively as it can cause damage to the gums (gingival tissue) (BPC 1968). • Oil is antiseptic and anti-putrescent; internal use as antispasmodic and carminative; used in phthisis and to reduce expectoration in coughs; applied locally to tooth cavity as antiseptic and analgesic (BPC 1934). Carminative for flatulent colic and with purgatives to prevent griping (Merck Index 1940). • External use: mixed with olive oil (2 parts) and applied to neuralgic areas; employed as embrocation for bronchitis, whooping cough and rheumatism (BPC 1934). Coriander oil: linalool (coriandrol: 65–70%), smaller amounts of ɑ-pinene, y-terpinene, limonene, p-cymene (over 40 constituents isolated) (Evans 2002). Attributes: carminative Use: • Added to purgatives to prevent griping (BPC 1968; Merck Index 1940; BPC 1934) Dill oil: primarily carvone (43–63%) and limonene. Other components dillapiole, myristicin (Evans 2002). Attributes: carminative Use: • Important component of infant gripe water for treatment of flatulence; useful vehicle for children’s medicines (BPC 1968; Merck Index 1940; BPC 1934).

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Eucalyptus (Eucalyptus globulus and other species)

Fennel (Foeniculum vulgare)

Ginger (Zingiber officinale)

Lemon (Citrus limon)

Nutmeg (Myristica fragrans)

Orange (Citrus aurantium)

Eucalyptus oil: at least 70% cineole. Attributes: decongestant, antiseptic Use: • Coughs, ENT (ear, nose and throat) infections and respiratory tract disorders (Evans 2002; BPC 1968). • Preparations: • Used in mixtures, inhalations, lozenges, pastilles; external use as ointments and liniments (Evans 2002). • Internal use in subacute and chronic bronchitis; cystitis, urethritis; by inhalation as vapour off boiling water for asthma, subacute/chronic bronchitis, pulmonary gangrene, influenza. External use in skin disease; topical application or spray to mucous membrane of nose and throat (Merck Index 1940). • Used in bougies, suppositories and pessaries as an antiseptic and to disguise the smell of iodoform (BPC 1934). Fennel oil: trans-anethole (60%), fenchone (10–30) (Evans 2002). Attributes: carminative Use: • Aromatic carminative employed with purgative medicine to prevent gripe and as Aqua Foeniculi (Fennel Water) for intestinal colic of children (Merck Index 1940; BPC 1934). Note: Powdered fennel used as flavouring in Compound Liquorice Powder with senna and sulphur (BPC 1968). Oil of Ginger (contains over 50 components): β-phellandrene, camphene, cineole, citral, borneol, zingiberene, β-bisabolene, farnesene, β-sesquiphellandrene, curcumene, zingiberol (Evans 2002). Attributes: carminative, stimulant; strong antibacterial and antifungal properties for some rhizome components (Evans 2002). Uses: • Anti-nausea medication; ginger root often prepared as a tincture, which was employed for making syrup (BPC 1968). • Stomachic, carminative for dysentery, flatulent colic etc; in toothwashes, ginger beverages and liqueurs (Merck Index 1940). Oil of Lemon: limonene (94%), citral (3.4–3.6%), citronellal, geranyl acetate (1%) (Evans 2002). Use: • Terpeneless Lemon oil (obtained by removal of terpene components) extensively used as flavouring agent; has a strong lemon flavour and aroma and is more readily soluble than the natural oil (BPC 1968; BPC 1934). Nutmeg oil: pinene, sabinene and camphene (60–80%), dipentene (8%), myristicin (4%), elemicin and isoelemicin (2%), safrole (0.6%), alcohols (6%); and minor amounts of eugenol, methyleugenol, methoxyeugenol, isoeugenol (total 1%) (Evans 2002). Attributes: carminative Uses: • Mild counter-irritant effect used in liniments and ointments, e.g. for rheumatism; used in hair lotions. • Added to purgative pills to prevent gripe (Merck Index 1940; BPC 1934). Note: Large doses stimulate the cerebral cortex and may induce epileptic-type convulsions (BPC 1968). Orange oils: there are two limonene-based oil types with similar chemical components, i.e. Bitter Orange oil (Essence de Bigarde) and Sweet Orange oil (Essence de Portugal). Other components: citral, citronellal, methyl anthranilate (indeed, over 62 components from Libyan fresh orange peel have been identified) (Evans 2002). Citrus aurantium subsp. bergamia has stronger flavour and aroma, and is more readily soluble. Bitter Orange flower oil: methyl anthranilate (0.1–1% gives characteristic aroma), linalol (18–42%), limonene (9–19%), linalyl acetate (3–16%), trans-nerolidol (1–9%), geranyl acetate (1.5–4%), ɑ-terpineol (2–7%) (Evans 2002). Use: • Terpeneless orange oil (removal of terpene components) has stronger flavour and aroma, and is more readily soluble than Orange oil; used as a flavouring agent. • Other preparations: Orange-flower water, syrup of orange flowers. Caution: Bitter Orange oil has phototoxic attributes that are not present in Sweet Orange oil (Tisserand & Balacs 1995).

FLOWERS OF THE MATERIA MEDICA Peppermint (Mentha x piperita: hybrid between M. spicata and M. aquatica)

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Oil of Peppermint: menthol (30–55%), menthone (14–32%), cineole (3.5–14%), limonene (1–5%), menthofuran (1–9%), isomenthone (1.5–10%) and menthyl acetate (2.8–10%), plus carvone, pulegone and viridofloraJ164 l (Evans 2002). Japanese Peppermint oil (Mentha canadensis var. piperascens): 70–90% menthol (Evans 2002). Attributes: carminative, antispasmodic, mild antiseptic Uses: • Widely used in tablets and lozenges; flavouring in dental preparations (Evans 2002). • Oil of Peppermint is an aromatic stimulant and carminative. It relieves gastric and intestinal flatulence and colic, and is employed with purgatives to prevent griping (BPC 1934). • Relief of nausea: it has been shown that this oil diminishes gastric acidity and shortens the emptying time of the stomach (Merck Index 1940). • Oil acts as a local anaesthetic (BPC 1934). • Oil of Peppermint may be administered on sugar, or in mixtures (Peppermint Water, Spirit of Peppermint). Peppermint lozenges are a mild carminative with a pleasant taste. Oil of Peppermint is mildly antiseptic, used to flavour dental pastes, powders and washes (BPC 1934).

‘Aromatic waters’ from the British Pharmaceutical Codex, 1968.

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Syrup of Ginger from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

During the latter part of the nineteenth century Eucalyptus oil gained international popularity and quickly entered into official pharmacopoeias across the world. The entry in the British Pharmaceutical Codex of 1934 is indicative, noting its value as an antiseptic and deodorant. It was regarded as being remedial for catarrhal inflammation of mucous membranes, especially of the respiratory tract and bladder. Pastilles containing the oil, often with menthol or red gum, were popular for head colds and sore throat. The oil, sprinkled on a handkerchief, was inhaled frequently for catarrhal colds and to prevent infection. An oil mixture with menthol, camphor or pine oil, was inhaled from a ‘dry’ inhaler as a decongestant. Steam-vaporised oil (sometimes with the addition of menthol, oil of pine and compound tincture of benzoin) was useful for cough relief in chronic bronchitis and asthma. Oily spray solutions and ointments for treating catarrh (mucous congestion) were prepared with eucalyptus and pine oils and other ingredients such as cocaine, menthol and/or camphor. In addition, a Eucalypt-based ointment (the oil mixed in soft paraffin) was employed for the treatment of burns and as a mild antiseptic dressing (BPC 1934).

 Ginger essential oil. (Courtesy Mountain Rose Herbs)

Eucalyptus drops. (Courtesy Felton Grimwade & Bosisto’s Pty Ltd)

Eucalyptus oil. (Courtesy Felton Grimwade & Bosisto’s Pty Ltd)

Food, water and shelter are the primary imperatives in establishing any new settlement – and the vegetable garden ranked high on the list of necessities in any pioneering venture. However, along with this type of garden many common ornamentals (and weeds) found their way into cultivation. The Asteraceae (Daisy) family would have been foremost among these plants – as they continue to be today. Numerous native species in this genus also have substantial therapeutic potential. The favourite medicinal herbs that were readily established included Marigolds, Chamomiles, Dandelion and various daisies. These plants were of significant value in a land where household remedies were usually the mainstay of medical care. Their therapeutic promise continues to expand their potential uses to this day – exceptional remedies with an equally exceptional future.

Chapter 2

ASTERACEAE: DAISIES OF THE APOTHECARY

Homoeopathic medicine kit. In many Australian households the mother took on the general doctoring, which could include the use of homoeopathic remedies. Homoeopathic medicine kits contained a fairly standard set of remedies, with travelling sales representatives calling around a couple of times a year to replenish used stock. Among the most common contents would be: Aconite for fevers; Arnica for injuries; Apis for fluid retention (swellings), insect bites or stings; Bellis for bruising; Nux vomica for nausea and ‘overindulgence’ (including hangovers); Camphora for collapse; Urtica for itching; and Sulphur for skin problems. (Image courtesy Martin & Pleasance, Port Melbourne)

The Garden Apothecary

The gardens of the early colonists had far more practical value than we can possibly imagine. They were not merely a culinary resource for herbs and spices. Many women used a basic first-aid kit and were very familiar with herbal remedies. There is where the conventional cottage garden became important. Common remedies acquired a special value in country regions, where there was usually a dearth of medical expertise. Indeed, even a few indigenous plants gained a measure of popularity. With a scarcity of medical supplies the cultivation of household remedies, where possible, was essential – and a surprising number were sourced from annual flowering plants.

The old and the new – wildflower gardens at the Chelsea Botanic Gardens, London (top), and the Brisbane Botanic Gardens. The Australian bush provides quite a different backdrop for wildflowers in comparison to the plants commonly found in European gardens – albeit many common medicinal herbs were imported and flourished in the ‘Great South Land’. 47

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Thus common remedies were by no means undervalued. The aromatic mints1, gingers, orange and lemon were favourites. While wound-healing herbs for treating infections and fractures predominated, small weedy plants such as the Dandelion and Chicory were premier liver tonics. Healing remedies from the Daisy family (Asteraceae) attracted particular interest, with some tried-and-tested herbs rating enough credit for inclusion in the official pharmacopoeias. Comfrey, the Common Daisy and Calendula provided household ‘wound-worts’ and antiseptics of inestimable value. The soothing effect of Chamomile was equally indispensable for irritable, teething babies, or as a carminative for stomach dysfunction. Indeed, many aromatic remedies that had flavouring qualities were familiar carminative agents. Australian Bush Flower Essences, developed by Ian White from native bush flowers, have a similar basis to the Bach Flower Remedies. There are 50 basic remedies – all of which have specific emotional indications for their use. (Image courtesy Australian Bush Flower Essences)

Rescue Remedy products. In the 1930s the Bach Flower Remedies were developed in England for the treatment of stress and emotional disorders. While very similar to homoeopathic medicines in that the flower essence is highly diluted, they differ somewhat in philosophy and preparation. Edward Bach believed that the dew collected from flowers contained various psychic properties of the plant, which were more potent when collected from blossoms grown in the sun. The flowers could be steeped in a bowl of sunlit water to prepare the remedy and preserved with brandy. One of the most famous of these remedies has been Rescue Remedy, for acute injuries and emotional trauma. (Image courtesy Martin & Pleasance, Port Melbourne)

It is important to note that numerous ordinary herbs were recognised medicines in professional circles. It should come as no surprise to find that many are still in use today – a lasting testimonial to their 1 Numerous herbal remedies with essential oil components are discussed in substantial detail in Volumes 1 and 2.

significant therapeutic value. Indeed, over the last few decades research efforts have not only validated their efficacy, but their potential has been expanded upon – giving many herbs a ‘new life’ in modern therapies. In addition, a few native remedies came into common use. Some of these had already carved out an established role in other traditions, particularly native species with close Asian relatives. They included an analgesic ‘Daisy Cress’ that was highly effective for easing toothache – as well as a few worthy relatives with antimicrobial, anti-inflammatory and woundhealing properties. These herbs did not escape the vigilant evaluation of the native flora in the search for medicines.

A Wound-wort of Distinction: Bellis perennis

The considerable reputation of the humble daisy as a healing herb has been largely forgotten today. Nicholas Culpeper (1653) held daisies in extremely high regard: The herb is under the sign Cancer, and under the dominion of Venus, and therefore good for wounds in the breast, and very fitting to be kept both in oils, ointments, plasters, and syrup. The greater wild daisy [Chrysanthemum leucanthemum] is a wound herb of great


Calendula flowers. The Daisy family (Asteraceae) has provided a remarkable number of exceptionally effective herbal medicines, albeit many remain underappreciated. While the scope of their medicinal recommendations could fill a volume such as this on its own, a few outstanding remedies with an ancient history of use deserve special mention. Their enduring role has seen them utilised in Australian herbal traditions since the arrival of the First Fleet, seeds of ancient medical traditions that migrated from Europe with the early settlers. (Image courtesy Berdan, Wikimedia Commons, CC-by-SA 3.0 Unported)

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Bellis perennis is widely naturalised throughout the southeastern part of Australia, ranging from southern New South Wales, to Victoria, adjacent regions of South Australia, and Tasmania. respect often used in those drinks and salves that are for wounds, either inward or outward. The juice or distilled water of these, or the small daisy [Bellis perennis], reduces the heat of choler, and refreshes the liver and other inward parts. A decoction made of them and drunk, cures wounds of the breast: also cureth ulcers and pustules in the mouth or tongue, or in the secret parts [genitals]. The leaves bruised and applied to the testicles or any other part that is swollen and hot, reduces the heat. A decoction made thereof, with wall-wort and agrimony, and placed fomented or bathed therewith warm, giveth great ease in palsy, sciatica, or the gout. The same also cures knots or kernels in any part of the body, and bruises and hurts that come of falls and blows; they are used successfully for ruptures and inward bruisings. An ointment made thereof heals all wounds that have inflammations about them, or by reason of running are kept long from healing. The juice of them dropped into the running eyes of any, cures them. As a poultice for sores they are good.

Bellis perennis, from Johann Georg Sturm, Deutschlands Flora in Abbildungen, 1795.

John Gerarde (1597) also recommended Bellis perennis for feverish conditions: ‘The decoction of the field Daisie (which is the best for physicks use) made in water and drunke, is good against agues’. Its analgesic attributes were held in equally high repute: ‘The

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Daisies do mitigate all kinde of paines, but especially in the joints, and gout, if they be stamped with new butter unsalted, and applied upon the pained place: but they worke more effectually if Mallowes be added thereto. The juice of the leaves and roots snift up into the nostrils, purgeth the head mightily, and helpeth the megrim [headache/migraine].’ The latter sounds very similar to the use of the native Australian Sneezewort (Centipeda cunninghamii). It is rather remarkable that the therapeutic reputation of this unassuming little herb seems to have arrived intact in more modern times. Indeed, some of the old recommendations appear as valid today as when they were written. The physician Dr Dorothy Shepherd held the daisy in equally high esteem: So the little Common Daisy on the green lawn is a valuable wound wort and a precious jewel in the crown of health we should all wear. A kind of Providence has planted it, where it is most needed, in the meadows near the country lanes, for the use of country men and women, for travellers, tourists, harvesters and soldiers on the march, who so heedlessly stamp on it in their daily round of toil. How often do we not overlook the little things which are meant for our good, and rush after some distant unobtainable chimera instead! (Shepherd 1969).

The use of Bellis perennis continues in homoeopathic traditions as a potent wound-healing ‘bruisewort’ with analgesic properties. Its main indications are for the treatment of weakness and the ‘bruised’ soreness that follows episodes of rheumatic pain, gout or general injuries – particularly where the symptoms are associated with exposure to cold.2 Bellis has been widely used for treating tumorous growths, especially those that develop following an injury. Additionally, the remedy has been useful for prolapsed conditions such as haemorrhoids or laxity of the uterine muscles, and has been considered a specific for the treatment of uterine congestion and enlargement. It continues to be utilised by many homoeopaths for this purpose and has often been recommended to deal with deep tissue injuries, including the side-effects of pelvic and breast surgery. Various investigations of the phytochemistry of Bellis perennis support its traditional use. The herb contains flavonol glycosides, phenolic acids, triterpenoid saponins and an essential oil. The antioxidant activity of 2 Edward Pollock Anshutz (1983) provides an excellent in-depth review of the homoeopathic use of this herb in New, Old and Forgotten Remedies (Narayana Publishers, Germany).

flower extracts was linked to its phenolic components, notably flavonol glycosides (Kavalcioğlu 2010; Siatka & Kasparova 2010). Interestingly, in Czech traditions Bellis has been utilised as an expectorant agent, as well as having diuretic, anti-inflammatory and vulnerary (woundhealing) properties, which has been largely attributed to its saponin components (Siatka & Kasparova 2010, 2003). Bellis perennis also has good antimicrobial potential. The essential oil components are antibacterial – as well as showing antimycotic (antifungal) activity against species of Trichophyton, Microsporum, Candida and Aspergillus niger, which was associated with a saponin complex (containing bellissaponins). Polygalacic acid glycoside components also possess activity against Candida and Cryptococcus yeasts (Kavalcioğlu 2010; Gudej & Nazaruk 2001; Avato 1997; Willigmann 1992; Bader 1990; Desevedavy 1989). Recently, saponin-based flower extracts have attracted interest as anti-cholesterol agents, showing an inhibitory effect on triglyceride levels. In addition, triterpene saponins (perennisosides) have anti-obesity potential (Morikawa 2011, 2010, 2008; Yoshikawa 2008). Studies have also suggested cosmetic uses for the common daisy. Extracts with a ‘skin-lightening’ property due to their effect on melanin biosynthesis have been proposed for use in hyperpigmentation disorders such as ‘age spots’ (John 2009; www.incosmeticsasia.com).

Comfrey: An Ancient Wound Healer Comfrey is an ancient herbal remedy with excellent wound-healing properties. Culpeper valued it highly:

The root being outwardly applied, cures fresh wounds or cuts immediately, being bruised and laid thereto: and is special good for ruptures and broken bones; so powerful to consolidate and knit together, that if they be boiled with dissevered pieces of flesh in a pot, it will join them together again. It is good for women’s sore breasts; also to repress profuse bleeding of the haemorrhoids, or piles, to cool the inflammation of the parts thereabouts, and to ease pain. The roots of comfrey taken fresh, beaten small, and spread upon leather, and laid upon any place troubled with the gout, presently gives ease; and applied in the samemanner it eases pained joints, and tends to heal running ulcers, gangrenes, mortifications, for which it hath by often experience been found helpful.


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Symphytum, syn. Comfrey root, Martindale Extra Pharmacopoeia, 1941. Symphyti Radix, Common comfrey root, Peter Squires, Companion to the latest edition of the British Pharmacopoeia, London, 1899.

Comfrey cream. (Courtesy Martin & Pleasance, Port Melbourne)

infections. The herb has even shown positive results for alleviating the pain associated with osteoporosis. Its healing effects are attributed to allantoin, which acts to promote granulation and tissue regeneration. It also contains a fair amount of mucilage, which has a demulcent effect, with polysaccharide components showing immunosupportive, anti-inflammatory and healing properties. Rosmarinic acid in the herb is also of value, showing anti-inflammatory, antioxidant and antimicrobial activity. Unfortunately, Comfrey also contains pyrrolizidine alkaloids (0.03%3) with detrimental potential – hepatotoxic, carcinogenic and mutagenic activity (PDR Herbal Medicines 2004; van Wyk & Wink 2004). It is therefore no longer recommended for internal use, or in cases where broken skin would allow greater absorption of the cream. 3 Not all pyrrolizidine alkaloids are toxic, and there can be substantial variability in the levels that are present in the herb. This means Comfrey’s harmful potential can vary significantly.

Analgesic Daisies Spilanthes and Acmella

Symphytum officinalis herb.

Although Culpeper possibly overstates its boneknitting attributes, Comfrey continues to be highly valued for injuries, although antibiotics would probably be more appropriate for serious

Acmella oleracea. (Courtesy Jeevan Jose)

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Northern Territory and Queensland to northern New South Wales – and var. brachyglossa extends to Papua New Guinea. • Spilanthes acmella is now placed in the closely related Queensland genus Blainvillea. • Blainvillea contains a couple of other native species, among them B. dubia, which is native to Far North Queensland; B. gayana4 is a tropical West African weed that has been found on the central Queensland coast. 4 In Senegal, Africa, this herb, despite its toxic reputation, was utilised medicinally – a decoction of the leafy stems or the powdered seeds as an antiseptic useful for eye problems (Burkill 1985).

Acmella grandiflora. (Courtesy Russell Cumming)

The Asteraceae family is prolific. It contains an extremely large number of genera (around 1650– 1700), of which some 300 are represented in Australia, albeit many of the species found here are imported ornamentals and weeds. A large number of Australian Daisies are very similar to those found overseas. This has made their botanical classification somewhat confusing – a situation compounded over time by the numerous weedy escapees. The identification of these plants can be quite difficult and those mentioned in the older literature were often placed in different genera to their classification today. The genus Acmella, although it contains only around 30 species, is widespread (the Americas, Australasia and the Pacific) with a couple of species introduced into Australia. Acmella oleracea (formerly classified as Spilanthes acmella or S. oleracea) is one of the more familiar medicinal herbs. Various native species from northern Queensland, which were formerly classified as Spilanthes, are now considered to belong to Acmella or Blainvillea: • Acmella grandiflora (including the varieties var. brachyglossa, var. discoidea and var. grandiflora), A. paniculata and A. uliginosa are found in Australia. • Acmella grandiflora has the most widespread distribution, from Western Australia, the

The wild Daisy Cress, Acmella grandiflora (syn. Spilanthes grandiflora), is a creeping tropical herb. Aboriginal people adopted the practice of chewing the roots without swallowing them as a toothache remedy on the Palmer goldfields in north Queensland – a custom thought to have been acquired from the Chinese immigrants (Webb 1959). Numerous closely related species had similar uses, including the flowers of the South African Spilanthes mauritiana, utilised as a toothache remedy by the Xhosa and Zulu. The remedy was reported to cause a tingling and numbness of the mouth for about 20 minutes – after which the toothache disappeared and did not recur. The herb was also recommended as an anti-rheumatic, as a treatment for headaches (the flower and fruiting top rubbed on the forehead), and as a snake-bite remedy (Watt & Breyer-Brandjwijk 1962). The widespread use of various Acmella and Spilanthes species for toothache is linked to the presence of a potent local analgesic substance (spilanthol, an alkylamide5) in the flowers. Spilanthol was originally found to be a difficult substance to extract due to its chemical instability – which may account Spilanthes mauritiana. for the variable activity (Courtesy Bart Wursten)


of herbal extracts, suggesting that the fresh plant would have been among the most effective forms to use. Spilanthol has an efficient numbing (analgesic) effect, as well as anti-inflammatory and antimicrobial properties. This makes it well suited for use in the treatment of painful conditions such as trauma, tendinitis and insect bites (Zakaria & Mohd 1994; Carle 1990a; Oliver-Bever 1986). Spilanthes and Acmella have provided highly useful febrifugal agents. In Papua New Guinea Spilanthes paniculata was a bath ingredient that helped to reduce the early symptoms of malarial fevers. The herb was taken to ease body pains, as well as for the relief of stomach-ache (Holdsworth & Mahana 1983). Evaluation of an antimalarial herbal medicine composed of Cassia occidentalis, Lippia chevalieri and Spilanthes oleracea showed that the last named, the Brazilian Cress, made a valuable contribution to its efficacy (Gasquet 1993). The closely related Beach Sunflower (Wedelia biflora) has been widely used in Southeast Asia as a leaf decoction for relieving periodic fevers and as an anti-malarial remedy (Perry & Metzger 1980). Indian medical traditions valued Spilanthes acmella for a great variety of conditions: bladder and kidney afflictions (including kidney stones), leucorrhoea (white vaginal discharge), scurvy, supression of menses (amenorrhoea), mouth sores, and paralysis of the tongue. The latter may have been due to its pungency – an attribute that inspired its use in places as diverse as Africa and India to induce salivation and ease mouth Spilanthes paniculata. (Courtesy JIRCAS, www. jircas.affrc.go.jp) (Below) Spilanthes acmella. (Courtesy Tim McCormack via CC-by-SA)

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soreness (Watt & Breyer-Brandjwijk 1962; Chopra 1956). Interestingly, Brazilian healers recommended the leaf and flower (infusion or decoction) similarly – for treating stomatitis, throat complaints, toothache and as a remedy for stammering (Holetz 2002). The herb was also reputed to have haemostatic properties (Oliver-Bever 1986). Spilanthol can readily permeate the buccal (oral cavity) mucosa and skin surfaces, which indicates good bioavailability and explains the fairly rapid efficacy of the remedy (Boonen 2010a, 2010b). In addition, Spilanthes acmella has been widely valued as a healing agent, with the leaf juice and bruised leaves applied locally to wounds or ulceration. The root infusion was a useful anti-inflammatory to ease the discomfort of psoriasis and other itching (pruritic) skin disorders – although it was noted to have purgative potential if taken internally (Quisumbing 1951). In the Philippines similar recommendations mention the use of Spilanthes acmella as a diuretic and solvent for renal calculi – and investigations have shown leaf extracts (alcohol-based) had diuretic properties similar to the conventional drug frusemide.6 Flower extracts have also demonstrated good diuretic properties. This is of interest because diuretics can have a useful antihypertensive effect – which is further supported by investigations showing that herb extracts (from aerial parts) possessed vasorelaxant (vasodilation) and antioxidant attributes (Yadav 2011; Wongsawatkul 2008; Ratnasooriya 2004). In India the herb even had a reputation as a tonic aphrodisiac that was said to be particularly valuable for sexual performance problems that occur with ageing. This effect was possibly linked to its alkylamide components (Sharma 2011). Modern research has tended to support many more of the traditional uses of these herbs (see Table 2.17).

5 Spilanthol is the most prevalent component of pharmacological interest, although other alkylamides are present in the herb (Boonen 2010a). See Prachayasittikul (2009) for further details of other bioactive metabolites. 6 Frusemide is primarily utilised in the treatment of hypertension, oedema and congestive heart failure (the latter being associated with significant oedema). Because the use of diuretics can result in low potassium levels (hypokalaemia), this has led to the development of combination products that incorporate this mineral. 7 For the sake of completeness, and to truly appreciate the enormous value of medicinal Asteraceae, herbs that have an established role in herbal medicine, i.e. Arnica, Calendula and Bellis, are outlined separately in the text.

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Kaurenoic Acid

Wedelia paludosa. (Courtesy Eduarda Mendes, flickr)

Kaurenoic acid and derivatives have shown interesting antifungal activity against Botrytis cinerea (Cotoras 2004). This is the fungus (appearing as dark brown balls in this image) that is utilised in wine making, although it can also cause significant grape crop losses under the wrong conditions. (Image courtesy Ninjatacoshell, Wikimedia Commons via CC-by-SA 3.0 Unported)

Kaurenoic acid is an active antimicrobial component that is present in many Wedelia species, including W. paludosa and W. trilobata – as well as a number of other genera, among them Annona, Xylopia and Aralia. It has demonstrated antibacterial properties against Bacillus cereus and Escherichia coli (Wilkens 2002) and Staphylococcus aureus (Okoye 2012) – as well as good activity against the oral (dental) bacteria Streptococcus mutans (de Andrade 2011). Kaurenoic acid and luteolin from the flowers of Wedelia paludosa (syn. Acmella brasiliensis) have shown antifungal properties against dermatophytes (Trichophyton and Epidermophyton spp.), which suggests The

potential for the treatment of skin infections (Bresciani 2004; Cechinel Filho 2004; Mottakin 2004; Sartori 2003; Block 1998b). anti-inflammatory and analgesic properties of kaurenoic acid are equally significant. Indeed, the activity of kaurenoic acid and luteolin was more potent than a number of standard analgesic drugs: acetyl salicylic acid (aspirin), acetaminophen, dipyrone and indomethacin (Block 1998a, 1998b). Kaurenoic acid therefore has potential as an anti-inflammatory topical application for skin disorders (Choi 2011; Boller 2010; Lim 2009), as a treatment for colitis (Paiva 2009) – and as an anti-asthmatic agent due to its significant antispasmodic properties (Hipolito 2011; Cho 2010; de Alencar Cunha 2003). There are a few other studies that suggest kaurenoic acid possesses vasorelaxant properties with antihypertensive potential (Tirapelli 2005, 2004, 2002; Ambrosio 2004); hormonal effects (a potent stimulatory effect on uterine contractions; Meena 2011) and anticancer (antiproliferative, cytotoxic and antitumour) activity. Various derivatives are under investigation for the development of specific anticancer products (Cuca 2011; Peria 2010; Cavalcanti 2009; Costa-Lotufo 2002). Brazilian studies of the antidiabetic potential of Wedelia paludosa extracts identified kaurenoic acid as one of the active hypoglycaemic compounds (Bresciani 2004; Novaes 2001). Furthermore, kaurenoic acid and some derivatives have shown antiparasitic activity against Leishmania (syn. Viannia) braziliensis (Brito 2006), Trypanosoma cruzi (Batista 2010, 2007, 1999) – and molluscicidal effects on the snail vector Biomphalaria peregrina involved in the transmission of schistosomiasis (Bardon 2007). Kaurenoic acid is present in substantial quantities (66 mg/fresh fruit) in the Cherimolia (Annona cherimolia) (Guillope 2011). It can also accumulate in the bark of Annona glabra (with small quantities in the leaves) (Oleviera 2002) and root bark of A. senegalensis (Okoye 2012) – which suggests that this compound is likely to be present in other Annona species such as the wonderfully sweet-flavoured Atemoya.


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sealant within honeybee hives. Sourced from the local flora, this soft, malleable substance usually has substantial antibacterial properties. While many medicinal claims have been made for propolis, its value can vary – depending upon the floral source. This would suggest that propolis sourced from Australian native beehives could have similar interesting chemical components, particularly if the product is harvested from areas where Wedelia herbs predominate.

Custard Apple or Atemoya (Annona squamosa x A. cherimolia).

Diterpenoids isolated from propolis sourced from the Brazilian Stingless Bee (Melipona quadrifasciata anthidioides) included kaurenoic acid, which displayed moderate antibacterial activity (Velikova 2000). Propolis is the resinous ‘glue’ that is employed as a structural

Australian Stingless Bees in hive. (Courtesy Russell & Janine Zabel)

Table 2.1 Summary of Investigations into ‘Daisy’ Herbs of Medicinal Value from the Genera Acmella, Spilanthes and Wedelia This brief overview summarises the main medicinal species utilised, with notations on the similar medicinal use of relatives (where applicable) – which may provide a valuable insight into the potential of related native Australian species. While the use of these herbs in Chinese and Indian traditions are included, this list is not exhaustive with regard to the use of these herbs in other countries. Category of activity and investigations Antimicrobial Spilanthes uliginosa (syns S. acmella, S. oleracea) • Extracts: demonstrated a wide range of antibacterial actions against Staphylococcus aureus, Salmonella typhi, Escherichia coli, Mycobacterium tuberculosis, Agrobacterium tumefaciens – as well as antifungal activity against Candida albicans, Trichophyton mentagrophytes and Aspergillus niger (Oliver-Bever 1986). • Extracts: good range of antibacterial activity, including activity against Corynebacterium diphtheriae and Bacillus subtilis (Prachayasittikul 2009). • Flower head extracts: good antifungal activity against agricultural pathogens (Fusarium oxysporum and F. moniliformis), as well as Aspergillus flavus, A. parasiticus (Rani & Murty 2006). • Antimicrobial attributes appear to be variable between the different species (and, possibly, different chemical races of the same plant). African samples of Spilanthes mauritiana showed only marginal antimycobacterial activity. However root and leaf extracts had antifungal potential against Aspergillus, although they were not active against Candida or Helicobacter pylori – a finding that highlights the ability of some plants to have a very specific activity against pathogenic organisms (Fabry 1998, 1996a, 1996b). • Extracts have shown antiviral activity (Oliver-Bever 1986). Root powder extracts have been utilised for treating HIV/AIDS and were reported to be very effective (Bajarang 2007).

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Spilanthes americana • Antibacterial activity against Staphylococcus aureus (Rojas 2006). Acmella (Spilanthes) calva • Antimicrobial (antibacterial, antifungal) activity: utilised for skin conditions, and has a rejuvenative reputation; decoction taken for dysentery in Bangladesh (Shanthi & Amudha 2010). • Extracts have antifungal activity against Fusarium oxysporum and Trichophyton mentagrophytes. Increased spilanthol content of extracts resulted in greater antifungal activity (Rai 2004). Spilanthes paniculata • Extracts showed good broad spectrum of activity against Salmonella paratyphi, Salmonella typhi, Vibrio parahemolyticus, Vibrio mimicus, Escherichia coli, Shigella dysenteriae, Pseudomonas aureus, Shigella boydii (Morshed 2011). Essential oil has specific antifungal activity against Microsporum gypseum (Trikunakornwong 1999). Wedelia chinensis • Leaf extracts possess highly effective wound-healing properties (Hegde 1994). • Extracts have demonstrated potent antibacterial properties against a range of bacteria: Staphylococcus aureus, Corynebacterium diphtheriae gravis, Streptococcus haemolyticus, Escherichia coli, Salmonella typhi (Duc Minh 1993). Wedelia biflora • The major component of the leaf oil extracted from the Beach Sunflower is α-pinene, a compound with antimicrobial properties (Cambie 1986). • Herb extracts: have shown antifungal properties against Rhizoctonia solani and Pythium ultimum (Miles 1990). Wedelia paludosa (syn. Acmella brasiliensis) • Good antifungal properties that appear to be linked to kaurenoic acid. Phytochemical investigations isolated kaurenoic acid, stigmasterol, oleanolic acid and a lactone (paludolactone) from fresh plant extracts. The kaurenoic acid content of the roots and stems could vary and was found to be higher during the autumn, which would therefore be the preferred time for harvest (Sartori 2003). Wedelia trilobata • Venezuelan studies: extracts showed an effective broad spectrum antibacterial action against gram-positive bacteria (Bacillus subtilis, Mycobacterium smegmatis, Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative bacteria (Proteus vulgaris, Pseudomonas aeruginosa, Salmonella group C, Salmonella paratyphi, Shigella sonnei). However, extracts did not show antifungal potential against Aspergillus flavus, Aspergillus niger, Mucor sp., Trichophyton rubrum or yeasts (Candida albicans, Candida tropicalis, Rhodotorula rubra) (Taddei & Rosas-Romero 1999).

Analgesic Spilanthes acmella (syns Acmella oleracea, Spilanthes oleracea) • Extracts possess significant local anaesthetic, analgesic and antipyretic activity (Ong 2010; Chakraborty 2010, 2004). Widely utilised in Southeast Asia (Malaysia and the Philippines) and India as a toothache remedy. • The genus has been recommended similarly in the medicinal practices of other countries: • Amazon: Spilanthes acmella, S. alba, S. ocymifolia (Schultes & Raffauf 1990). • Africa: S. mauritiana (Watt & Breyer-Brandwijk 1962). • Bangladesh: Spilanthes calva leaf and flowers used for toothache and as a local anaesthetic and analgesic remedy (Shanthi & Amudha 2010; Alam 1992). Wedelia biflora • Analgesic (antinociceptive) properties, along with W. trilobata and Eclipta alba (Sureshkumar 2007). Wedelia paludosa (syn. Acmella brasiliensis) • Kaurenoic acid and luteolin have shown potent antinociceptive activity (Block 1998a, 1998b). Wedelia chinensis • Leaf extracts: demonstrated substantial analgesic activity (Sureshkumar 2005).

Antidiabetic and metabolic potential Wedelia paludosa • Extracts were shown to lower blood glucose, with kaurenoic acid identified as one of the active hypoglycaemic compounds (Bresciani 2004; Novaes 2001).

Neurological activity Spilanthes acmella var. oleracea • Brazilian investigations revealed an interesting convulsive property of this plant; this resulted in its proposed use in experimental models of epilepsy (Moreira 1989). • S pilanthes acmella flower bud extracts had lipase-inhibitory properties with potential for development as an anti-obesity remedy for weight reduction. However, in this study Aframomum meleguetta seed extracts showed a much higher activity (Ekanem 2007). Wedelia chinensis • Plant extracts: potent anticonvulsant activity (Mishra 2011), as well as CNS depressant properties (Suresh 2010; Prakash 2008). Antioxidant properties of plant extracts, as well as anti-stress activity against brain neurotransmitters and enzyme MAO (monoamine oxidase) (Verma & Khosa 2009).


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Urinary tract disorders Spilanthes acmella • Flower extracts demonstrated strong diuretic effect that supports traditional use in Sri Lankan herbal medicine (Ratnasooriya 2004); leaf extracts have shown diuretic properties (Yadav 2011).

Immunological, antioxidant and anti-inflammatory activity Spilanthes acmella • Spilanthol and kaurenoic acid have significant anti-inflammatory activity (Wu 2008). • Extracts have good antioxidant properties (Prachayasittikul 2009; Wongsawatkul 2008), and significant anti-inflammatory and antipyretic activity (Chakraborty 2010, 2004). • Leaf extracts: substantial immunomodulatory (immune-supportive) activity (Rajesh 2011; Sayadi 2010). Acmella (Spilanthes) calva • Anti-inflammatory, antimicrobial (antibacterial, antifungal): tincture used to treat inflammatory jaw problems; popular use for skin disorders, strengthening effect on collagen and used in anti-wrinkle, anti-ageing skin formulations (Shanthi & Amudha 2010). • Whole plant extracts have also shown significant antioxidant potential, largely (94%) due to phenolic components, with carotenoids making a smaller contribution to its activity (Sikder 2010). • Extracts of the herb, which are added to chewing tobacco in India, have shown antimutagenic potential (Sukumaran & Kuttan 1995). Wedelia chinensis • Leaf extracts: anti-inflammatory activity comparable with aspirin and indomethacin (Sureshkumar 2005). Caffeic acid derivatives present in the herb, of which wedelosin has shown anti-inflammatory properties (Apers 2002). Wedelia (Sphagneticola) trilobata • Kaurenoic acid: analgesic (antinociceptive) and anti-inflammatory activity (Mizokami 2012). • Wound-healing and antibacterial activity of kaurenoic acid from leaf extracts (Balekar 2012).

Antiparasitic activity Spilanthes acmella • Extracts have shown good antimalarial activity with clinical potential (Gasquet 1993); antiplasmodial activity: N-alkylamides isolated as synergistic active components (Mbeunkui 2011). • Insecticidal activity against head lice (Pediculus humanus); flower extracts were the most effective (Ramdev 2011). • Plant extracts were anthelmintic against Hymenolepis nana and antiprotozoal against Entamoeba histolytica (Watt & Breyer Brandjwijk 1962). Spilanthes calva • Whole plant, flower heads: recommended in scabies treatments in Bangladesh (Alam 1992). • Affinin (spilanthol) shown to be the molluscicidal component of some Asteraceae herbs, i.e. Heliopsis longipes, Wedelia parviceps, Spilanthes oleracea (Johns 1982). Wedelia paludosa • Antiprotozoal activity against Trypanosoma cruzi, the organism responsible for Chagas disease (trypanosomiasis), could be linked to its kaurenoic acid content (Batista 2010, 2007, 1999). Wedelia trilobata • Kaurenoic acid has shown potent leishmanicidal activity against Leishmania braziliensis (Brito 2006). Wedelia subvaginata • Argentinian studies have shown herb extracts had molluscicidal effects on Biomphalaria peregrina (Bardon 2007).

Liver-protective (hepatoprotective) properties Spilanthes ciliata • Extracts gave significant protection against aflatoxin-induced liver damage (Shyamal 2010). Wedelia chinensis (syn. W. calendulacea) • Extracts have shown anti-hepatotoxic properties that protect the structural and functional integrity of the liver. Significant protective effects from liver damage due to paracetamol, D-galactosamine and carbon-tetrachloride toxicity. It has also shown experimental activity against hepatitis B. The herb had a substantial cholagogic effect and acted to strongly stimulate bile flow (Bhawna & Kumar 2010; Saleem 2010; Murugaian 2008; Emmanuel 2001; Lin 1994; Gopalakrishnan 1989; Sharma 1989; Yang 1987, 1986). Wedelia paludosa (syn. Acmella brasiliensis) • Significant protective effect of extracts on paracetamol-induced hepatotoxicity in mice (Meotti 2006).

Insecticidal, mosquitocidal and toxic potential Spilanthes acmella • Crushed plant and fruit used as insecticide and piscicide in India; flowers are powerful mosquito larvicide (Watt & BreyerBrandjwijk 1962; Chopra 1956). • Plant extracts: have shown excellent larvicidal activity against mosquito vectors for malaria and filariasis (Pandey & Agrawal 2009). Kaurenoic acid has larvicidal and trypanocidal activity (Haraguchi 2011; Block 1998a).

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• S pilanthol (and some other components) has useful insecticidal properties that support the popular use of the Spilanthes genus against bedbugs and cockroaches (Watt & Breyer-Brandjwijk 1962). Spilanthes calva • Significant anti-feedant activity against Helopeltis theivora, a pest of the Tea plant, Camellia sinensis (Dolui & Debnath 2010). • Mosquito larvicide: Some species are very useful for killing mosquito larvae (larvicidal activity). Spilanthes acmella extracts (plant, flower bud) and spilanthol showed good activity against the vectors for filaria (Culex quinquefasciatus) and malaria (various Aedes species). Spilanthes calva and S. paniculata: also active as larvicides, albeit to a lesser extent (Ramdev 2011; Pandey 2011, 2007; Ramsewak 1999; Pitasawat 1998; Oliver-Bever 1986). • Piscicidal activity (fish poison): Spilanthes flower heads used to cause stupefaction of fish. West African tribes utilised Spilanthes mauritiana for this purpose. Experimentally, a volatile oil extracted from the plant was shown to be highly toxic to fish (Watt and Breyer-Brandjwijk 1962). • Leaf powder: used in Bangladesh as a fish poison with the addition of DDT (Alam 1992). This was found to be highly effective; DDT acted more slowly than spilanthol but its activity was five times more potent (Watt and Breyer-Brandjwijk 1962). Wedelia biflora • Stem and leaf extracts have shown anti-feedant activity against the Cotton boll weevil (Meena 2011; Miles 1990). • Anthelmintic activity for root extracts (Prakash Yoganandam 2009a). Wedelia chinensis • Insecticidal and insect-repellent activities (Baki 2005; Xian 2005, 2003; Pang 2000). Wedelia glauca • Oil has been evaluated against the honeybee mite, Varroa destructor, although Schinus molle had greater selectivity against the parasite (Ruffinengo 2005).

Remarkable Arnica (Arnica montana)

Arnica cream. (Courtesy Arnica oil. (Courtesy Martin & Pleasance, Port Dr. Reckeweg & Co., Melbourne) Bensheim, Germany)

Of all the Asteraceae, there is one notable herb that rates highly for the treatment of traumatic injuries – the yellow-flowered Alpine Daisy, Arnica montana. This outstanding remedy has been used for centuries for trauma and bruising, and its effects can be dramatic. If employed immediately after an accident it reduces the tissue damage in a truly remarkable manner. However, in herbal medicine it is only used externally due to its irritant potential. The British Pharmaceutical Codex of 1934 recognised both the flower and root as official: ‘Arnica flower has an irritant effect upon the stomach and intestines.8 As a local application for sprains and bruises, where the skin is not too

Arnica montana, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

tender or broken, the tincture, Tinctura Arnicae Floris, has been employed.’ The Codex also noted: ‘The action of arnica rhizome is the same as that of the flower. The tincture, with or without dilution with water is a popular application for sprains 8 Taken internally, poisoning is associated with symptoms of severe gastroenteritis, nervous system distress (nervousness, irritability), accelerated heart rate and muscular weakness. Fatalities, albeit rare, have been recorded in the older literature.


and bruises when the skin is unbroken. Liniment of arnica is applied with friction as a mild counterirritant, but cases of arnica dermatitis from the local application of arnica preparations have been reported.’ Although its use is to be avoided on open wounds, it can be applied around the injury site, as long as it is used only on non-broken areas of skin. However, Arnica has been extensively employed as a homoeopathic for internal use, having significant anti-shock and healing effects in cases of traumatic injury. Recently, clinical studies have suggested that it may also be useful as a topical application in osteoarthritis of the knee (Knuesel 2002). There are some additional

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interesting investigations of the herb that found extracts (particularly the phenolic components) had a detoxicant effect on liver function. Polysaccharides with immunomodulatory properties were isolated, as well as a number of cytotoxic sesquiterpenes, including helenalin (Iamemii 1998; Iaremii 1998; Woerdenbag 1994; Puhlmann 1991; Marchishin 1983). Helenalin is of particular interest as an anti-inflammatory and anti-tumour component, with antibacterial, anti-trypanosomal and anti-plasmodial activity – however, it is also highly toxic (Boulanger 2007; Huang 2005; Jimenez-Ortiz 2005; Francois & Passreiter 2004; Schmidt 2002; Lyss 1998; Powis 1994; Chapman 1988). Extracts were also active against dental bacteria – although their effectiveness could vary (Iauk 2003; Koo 2000).

Beach Sunflowers and Singapore Daisies

Wedelia asperrima. (Courtesy Russell Cumming)

Arnica, from Peter Squires, Companion to the latest edition of the British Pharmacopoeia, 1899.

Wedelia is another genus in the ‘daisy’ classification that is closely related to Spilanthes and Acmella – and a number of species are Australian natives: • Wedelia asperrima, the Sunflower Daisy: found throughout the northern tropics, ranging from the coast to inland sites – Western Australia (northwest), Northern Territory, northern Queensland. • Wedelia longipes: Northern Territory and northern Queensland (Cairns, Cape York). • Wedelia spilanthoides: found throughout much of Queensland, ranging from the tropics to northern New South Wales – also has limited distribution in the Northern Territory and extends to Papua New Guinea.

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• Wedelia biflora (recently reclassified as Melanthera biflora, syn. Wollastonia biflora), the Beach Sunflower, has a similar distribution to Wedelia spilanthoides. Beach Sunflower is common along the Queensland coastline, ranging to northern New South Wales. It is also found in the Northern Territory – as well as Oceania and Southeast Asia. • Wedelia stirlingii, W. urticifolia and W. verbesinoides: these three species are native to Western Australia and the Northern Territory9, with W. stirlingii extending its range to South Australia and Queensland. • Wedelia trilobata (now Sphagneticola trilobata)10, the Singapore Daisy: considered to be a major pest along the Queensland coastline, extending into the Northern Territory and tropical Western Australia. The herb originates from Central and South America (Mexico to Argentina).

Melanthera integrifolia, flower detail and coastal habitat. (Images courtesy Kim & Forest Starr, Hawaii)

The Beach Sunflower (Melanthera biflora syn. Wollastonia biflora, formerly Wedelia biflora) is a native Sunflower found along the east coast of Australia that ranges to the Indo-Pacific region and would appear to be suitable for coastal revegetation projects. Indeed,

the closely related Hawaiian Melanthera integrifolia is a heat, salt and wind tolerant species that has been utilised for erosion control, and as a long-lived groundcover that does not have invasive tendencies.

Beach Sunflower (Melanthera biflora). (Image on right courtesy Russell Cumming) 9 There are also a couple of, as yet, unnamed species from WA (sp. Hamersley) and the NT (sp. Limestone). 10 Most of the literature will be found under Wedelia trilobata.


The Beach Sun-flower has attracted little attention in Australia as a medicinal plant, although it does have a good reputation as a wound-healing herb overseas. The leaf poultice, or the juice squeezed from the leaves, was easily applied to sores, wounds, insect bites, swellings, scabies and numerous festering forms of skin problems (Perry & Metzger 1980). In Tonga the leaf juice (extracted by pounding the leaves between hot stones) was applied to serious wounds, including injuries contaminated by the tetanus bacterium (Cribb & Cribb 1985; Weiner 1985). The leaves were combined with ginger for treating venereal disease in Singapore. The fresh roots (decocted) provided a traditional medicine in the Philippines for gynaecological disorders, being utilised as an emmenagogue, for leucorrhoea, and other infections.11 It was also taken to ease stomachache, and as a diuretic. While the roots had a slight purgative action, the use of the flowers was avoided as their action was said to be much more drastic (Perry & Metzger 1980; Quisumbing 1951; Burkill 1935). Fijian medicine has utilised the Beach Sunflower in an equally diverse manner. The liquid pressed out of the young leaf buds was taken to ease ‘pains in stomach’ and nausea (Weiner 1985). The leaf decoction provided a remedy for bacillary dysentery, hepatitis, haemorrhoids and bladder infections. The herb was incorporated into treatments for appendicitis, eczema, muscular spasms, convulsions, stomach-ache and fish poisoning. Leaves soaked in coconut oil provided a liniment for massaging sprained or bruised limbs (Cambie 1986). Somewhat more unusual was the recommendation that a liquid (pressed from the leaves) was useful for testicles swollen due to ‘cold’ and diarrhoea. To encourage urination, or for the relief of testicular swelling associated with herniation, the liquid from the stem was used (Weiner 1985). The Beach Sunflower has had a similarly varied and indispensable medicinal role throughout Papua New Guinea. The leaf or stem was used to make remedies (usually a water-based drink) for diarrhoea, dysentery and stomach-ache – or to allay coughing problems (leaf infusion). In the Central Province and Manus the leaf or stem sap was applied to bleeding cuts to encourage blood clotting and form a protective scab. In Madang 11 Some of these uses may be linked to the antibacterial and uterine stimulant effects of kaurenoic acid.

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Province sap from the heated leaves was dripped onto tropical sores, or rubbed onto scabies infections. In Morobe Province the fresh leaf sap was applied to centipede bites. Additionally, the leaves provided a useful warm compress for general pain relief. In New Britain (Buka Island) an infusion (the leaves crushed and mixed with seawater) was taken for malarial fevers. The leaves were also a popular analgesic to ease headache or toothache pain (Woodley 1991; Holdsworth 1984; Holdsworth & Lacanienta 1981).

Sunflower Daisy (Wedelia asperrima). (Courtesy Russell Cumming)

The Sunflower Daisy (Wedelia asperrima) is very similar in appearance to the Daisy Cress (Acmella grandiflora) – although Sunflower Daisy leaves have a softer texture and the shape of the flower head differs somewhat. While the Daisy Cress is nontoxic, Sunflower Daisy is a known stock poison – albeit animals generally find the plant highly unpalatable and will not eat it unless desperate. It contains a chemical called wedeloside that acts to block the cellular use of oxygen, resulting in cell death. In particular, it disrupts liver function. In sheep and cattle, poisoning occurs within 24 hours of eating it and, although the symptoms may not be apparent until 18 hours after ingestion, when they manifest death generally occurs within 30 minutes (Dowling & McKenzie 1993; Lewis 1981; Everist 1981). In South America, studies have also implicated Wedelia glauca (now Pascalia glauca) as a stock poison (Tapia 1996; Collazo & Riet-Correa 1996).

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Singapore Daisy: A Problematic Groundcover

Singapore Daisy

The Singapore Daisy (Wedelia trilobata, now Sphagneticola trilobata) has been somewhat misguidedly introduced around the world as a golden-flowered groundcover. In many regions it has subsequently achieved serious pest status and is almost impossible to eradicate. The weed has a particularly invasive reputation in the Australian tropics. The plant, which tends to persist despite the use of herbicides or manual extraction, has a very quick growth habit, particularly under hot, humid conditions. It rapidly forms a thick carpet over the ground and, while this may be a blessing for preventing weedy invasions in the urban garden, in the tropical forest it quickly becomes an insurmountable barrier to seedling growth. The fact that the weed can readily spread to remote sites during the wet season floods adds to its invasive potential. In Central America and the Caribbean, the herb has been utilised as a remedy for the treatment of sores, swelling, stubborn non-healing wounds and painful arthritic disorders (Balekar 2012). In Belize it had a medicinal reputation similar to various other Wedelia species: for the treatment of hepatitis, indigestion due to sluggish liver, white stools, urination problems (dysuria, anuria) and infections. Externally, the wash or bath was considered useful for muscle cramps, and rheumatic pain or swellings. The fresh leaves were also poulticed locally for the relief of arthritic pain (Arvigo & Balick 1993). The leaf tea has been used as a cold and flu remedy, or poulticed on skin problems such as sores. Furthermore, it has a reputation for use in gynaecological (menstrual) disorders, abortion and to clear the placenta following birth (Meena 2011). Certainly, the latter suggests that the herb may have hormonal effects. The main components of interest were kaurenoic acid, eudesmanolide lactones and luteolin. Experimentally, kaurenoic acid had a potent stimulatory effect on uterine contractions. Investigations have verified that extracts of Singapore Daisy also possess anti-inflammatory, analgesic and good broad-spectrum antibacterial activity (Balekar 2012; Mizokami 2012; Meena 2011).


Wedelia chinensis (formerly W. calendulacea) is an important herb of Asian origins. While it does not occur in Australia it deserves mention due to its considerable medicinal reputation. The remedy has tonic, anti-inflammatory, antitussive, antimicrobial and alterative properties. It has a rather extensive therapeutic repertoire, particularly for respiratory disorders including the treatment of bronchitis, pneumonia, whooping cough, haemoptysis (spitting blood), pharyngitis, tonsillitis, influenza, coughs, colds and headache. The herbal decoction (seeds, flowers and/or leaves) has been valued as a deobstruent – a substance that removes obstructions in the body by opening up the natural passageways or pores. This was the basis of its febrifugal effect in fevers. Chinese Wedelia gained a particular reputation for the prevention of measles and diphtheria and their complications. The herb is considered useful for various inflammatory conditions including articular inflammation (arthritis), cystitis (bladder infections) and laryngitis. It has also been recommended in Chinese and Malay traditions as an anti-hypertensive remedy. Furthermore, the leaf juice was frequently utilised as a snuff for headaches. In India the leaves provided a hair dye that was considered useful for promoting hair growth (Zakaria & Mohd 1994; Hong Kong CMRI 1984; Quisumbing 1951). Interestingly, Eclipta alba, a herb that has been used as a Wedelia substitute12, has a similar reputation for encouraging hair growth that has been supported by animal studies (Roy 2008). Substantial pharmacological evaluations of Wedelia chinensis support its clinical reputation. The antimicrobial and anti-inflammatory effects of the fresh leaf juice explain the herb’s efficacy in inflammatory skin conditions, including impetigo, abscesses, mastitis, boils and furunculosis (recurring boils). It has been utilised as an additive to baths for easing prickly heat rash (Van Dan 1993; Duc Minh 1993). Chinese Wedelia has a particularly good reputation as a liver-protective herb, and has therefore been recommended for hepatitis, hepatic and splenic enlargement – which has been supported by investigations showing strong hepatoprotective 12 Eclipta also has dye qualities and has been used as a tattooing agent, the juicy green leaves being rubbed over the scarifications to impart a deep bluish-black colour (Meena 2011).

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activity (see Table 2.1). The plant contains a variety of compounds that include saponins, tannins, isoflavonoids, carotenoids and wedelolactone which contribute to its complex pharmacology (Emmanuel 2001; Sharma 1989; Yang 1986). The plant decoction has also been taken as a haemostatic to ease menorrhagia (excessive menstrual bleeding) or uterine haemorrhage. Investigations of extracts have found a protective effect against osteoporosis – which may be linked to isoflavones and wedelolactone, components that possess phytoestrogenic properties (Annie 2006).

A Weedy Medicinal: Eclipta alba

Eclipta alba (syn. E. prostrata). (Images courtesy Kim & Forest Starr, Hawaii)

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Eclipta herbal preparation. (Courtesy Acuneeds Pty Ltd, Sydney)

In some traditions Eclipta alba (syn. E. prostrata) has been utilised as a substitute for Wedelia calendulacea. Its use in India for liver and gall bladder disorders has been similar to that of Wedelia – and it has also provided a substitute for Dandelion (Taraxacum officinale). The remedy was highly recommended for jaundice and splenomegaly, and has shown potential benefits in hepatitis. Studies of Eclipta alba have verified its hepatoprotective activity, as well as regenerative effects on the liver. The herb contains coumestans (wedelolactone, nor-wedelolactone, desmethylwedelolactone) that are similar to those found in Wedelia – with the hepatoprotective effects primarily linked to wedelolactone (an anti-inflammatory compound) and desmethylwedelolactone. Clinically, Eclipta alba has been effectively combined with various other hepatoprotective herbs – Phyllanthus fraternus, P. niuri and Curcuma longa. Studies of a compound remedy called Tephroli (sourced from Tephrosia purpurea, Eclipta alba, Andrographis paniculata, Terminalia chebula and Ocimum sanctum) showed good results for the treatment of jaundice and viral hepatitis, with a concurrent significant improvement in

liver enzyme chemistry. Eclipta herb extracts have also demonstrated analgesic and antiviral properties – including activity against HIV – which support its use in Thai medicine for AIDS patients (Mithun 2011; Bhwana & Kumar 2010; Patel 2008; Tewtrakul 2007; Singh 2001, 1993; Zhang & Guo 2001; Mi 1997; Saxena 1993; Wong 1988; Chandra 1987; Jayaram 1987; Gopalakrishnan & Jayanthi 1986; Gupta 1986; Wagner 1986; Sankaran 1984; Satyavati 1976). Indian herbal traditions consider Eclipta alba to have general tonic properties useful as an antiageing remedy and in debility. It has digestive tonic (increase appetite, improve digestion) and bowel regulatory properties – as well as being useful for eye and ear infections. The herb has long been well regarded in treating diverse skin disorders, particularly as a wound-healing application for inflammation, cuts or burns,13 with the fresh leaf having a good reputation as a styptic agent (Mithun 2011). The leaf juice, combined with honey, was given to infants to treat catarrhal congestion and upper respiratory tract infections. Studies have shown antimicrobial (antibacterial, antifungal, anti-candidal) effects for various plant extracts – with light exposure having an interesting enhancement effect (Wiart 2004; Satyavati 1976). Extracts also had effective larvicidal activity against Aedes fluviatilis mosquitoes (Macedo 1997). The use of Eclipta as an antidiabetic remedy in Indian traditions prompted investigations into its hypoglycaemic attributes – which were found to be quite potent. Extracts also demonstrated good antioxidant and cholesterol-lowering properties. Moreover, it has shown analgesic and immunostimulant activity in animal studies, and has been incorporated into compound formulations for use in immune disorders with herbs such as Astragalus membranaceus and Ligustrum lucidum (fruit) (Mithun 2011; Jayathirtha & Mishra 2004; Sawant 2004; Liu 2000; Ananthi 2003; Bhattacharya 1997; He 1992). Other studies have indicated that the 13 The root can also be a useful local antiseptic for ulcers or wounds, especially for cattle. However, it has emetic and purgative properties if taken internally.


herb also contains a number of components with anticancer potential: wedelolactone, luteolin, luteolin 7-O-glucoside and saponins (dasyscyphin-C and eclalbasaponin I) (Liu 2012; Mithun 2011). Indian traditions have utilised Eclipta alba as an antidote for snake bite. This is supported by a few intriguing investigations showing that extracts inactivated snake venom, exhibiting antimyotoxic (muscle toxin) and antihaemorrhagic effects. These activities were primarily attributed to wedelolactone, although stigmasterol and sitosterol were other anti-venom and antiinflammatory components in the plant extract. In Trinidad the leaf juice also has a reputation as an anti-venom agent against scorpion stings (da Fonseca 2010a; Pangal 2010; Diogo 2009; Perumal Samy 2008; Pithayanukul 2004; Syed 2003; Lans 2001; Melo & Ownby 1999; Melo 1994; Mors 1989).

Scorpion drawing (Heterometrus indicus) from JFW Herbst, Natursystem der Ungeflügelten Insekten, 1880. Eclipta alba has shown antidotal effects, including activity against snake venom and scorpion stings. While scorpions have a highly toxic reputation, only a few species (around 25) are known to contain a toxic venom that can result in fatalities.

Chinese Wedelia as an Anticancer Remedy

Wedelia chinensis. (Courtesy Lorenzarius, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

Herba Wedeliae (Wedelia chinensis) has been utilised as an anticancer treatment in Chinese medicine, primarily in formulations for cancer of the larynx and colon. The History of Medicinal Herbs in Fujian provides a comprehensive outline of its medicinal reputation: ‘The drug cures diphtheria, pharyngitis, tonsillitis, pneumonitis, pulmonary ulcer, whooping cough, nasorrhagia [epistaxis], haemoptysis caused by tuberculosis, haematuria, dysentery, measles, infectious hepatitis, rheumatic arthritis, insomnia caused by violent restlessness, gingivitis, carbuncle, and furuncle’ (Chang 1992). Many of these indications appear to draw on a measure of support for the immune system, as well as its significant antibacterial, anti-inflammatory and analgesic properties. Chinese Wedelia possesses a substantial vulnerary effect, ‘drawing out’ infection and actively healing wounds, particularly those due to ulceration or fistula. In cancer of the parotid gland the herb was pounded to a paste with the bulb of Allium bakeri and applied locally. The remedy has been well regarded as a detoxicant that will clear ‘heat’ (inflammatory symptoms). Inflammation is an important part of the process that supports tumour growth as well as its invasive and metastatic potential (Chang 1992).

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Wedelia chinensis extracts have good experimental anticancer activity. Recent investigations indicated excellent chemopreventive activity against sarcoma development in mice (Halder 2011; Meena 2011; Gupta 2007). Wedelolactone, luteolin, apigenin and indole-3-carboxylaldehyde are among the antitumour components that were identified with good effects against prostate cancer in animal studies (Tsai 2009; Lin 2007). Wedelolactone, in particular, can reduce the growth of various cancer cells and has been utilised in numerous experimental studies (Benes 2011; Vender 2008; Kobori 2004). Another potential anti-tumour compound, wedeloside, has been isolated from Wedelia asperrima (Oelrichs 1980). Kaurenoic acid is another antitumour component that is widespread in the genus (Peria 2010).

Classic Chamomile

The Chamomiles are attractive daisy-like herbs that can be quite difficult to tell apart. Both Matricaria chamomilla and M. recutita are among the naturalised remedies in Australia that were important components of the household medicine cabinet. (Image courtesy Erin Silversmith)

The name ‘Chamomile’ can be somewhat deceptive as it can refer to a number of herbs with a similar appearance. Their identification has been characterised by substantial confusion, in the use of both botanical and common names: • German Chamomile, Matricaria recutita (syns M. chamomilla, Chamomilla recutita) is also known as the Wild or Hungarian Chamomile. • Roman Chamomile, Chamaemelum nobile (syn. Anthemis nobilis) is also known as the English, Garden, Lawn, Scotch, Sweet or True Chamomile). The Corn Chamomile (Anthemis arvensis) is a • different species.

Wild Chamomile growing beside a wheat field.

For decades, the identification of herbal products sourced from Roman Chamomile and German Chamomile was utterly confused. Their similarity of appearance resulted in numerous instances of misidentification – as well as incidents of substitution and adulteration that have been almost impossible to detect. Much of the older literature stated that Roman Chamomile oil had very similar activities to that of the German Chamomile, although later texts make a clear distinction between the two species.


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Calendula arvensis. (Courtesy Zachi Evenor, http://www. flickr.com/people/zachievenor)

Analyses of Matricaria recutita have shown it is distinguished by sesquiterpenes (azulene, bisabolol and derivatives), coumarins (umbelliferone, herniarin) and flavonoids (mainly apigenin, also quercetin, patuletin, luteolin and glycosides). Commercially, German Chamomile products are made from fluid extracts with a required minimum content of chamazulene and ɑ-bisabolol14 as the marker constituents. Tinctures prepared from Chamomile flowers (extracted with 30, 50 or 70% alcohol) require a ratio of 20 per cent flower weight per volume of alcohol. The alcohol content ensures that the constituents of the tincture are similar to that of alcohol-extracted essential oils (Mann & Staba 1986). Interestingly, a higher yield of essential oil can be obtained from the extraction of frozen flowers, rather than utilising the dried product (Carle 1989). German Chamomile (Matricaria recutita) and Roman Chamomile (Chamaemelum nobile) have similar, albeit not particularly potent, antibacterial properties. German Chamomile oil was shown 14 The Brazilian tree Vanillosmopsis erythropappa (Asteraceae) has been used as an adulterant of Chamomile oil. It contains up to 3% essential oil with a high concentration of ɑ-bisabolol (Carle 1990b) – a compound with significant antispasmodic activity (Achterrath-Tuckermann 1980). ɑ-bisabolol from Chamomile oil has also shown anti-leishmania activity with potential for use in the treatment of leishmaniasis (Morales-Yuste

The Corn Chamomile (Anthemis arvensis), from Prof. Dr. Otto Wilhelm Thomé, Flora von Deutschland, Österreich und der Schweiz, 1885, Gera, Germany. The Corn Chamomile (A. arvensis) and Stinking Chamomile (A. cotula) are naturalised in the temperate parts of the continent – primarily New South Wales, Victoria, South Australia and Tasmania. The Golden Marguerite or Yellow Chamomile (A. tinctoria, syn. Cotula tinctoria) is also naturalised in Tasmania and South Australia.

to be slightly more effective than that of Roman Chamomile – although the Moroccan ‘Chamomile’ (Ormenis multicaulis, syn. Cladanthus multicaulis) had a higher level of activity. German Chamomile oil does have active antifungal properties – although there are other oils, such as Thyme and Cinnamon, that are more effective at a lower concentration. Clove, Cinnamon and Thyme also possess more potent antimicrobial properties. Nevertheless, this does not preclude an appreciation of Chamomile’s antimicrobial effect when utilised as a woundhealing, anti-inflammatory agent (McKay & Blumberg 2006; Lis-Balchin 1998).

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Anthemis cotula, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. Anthemis cotula has sometimes been identified as a contaminant of German Chamomile, and contains anthecotulide, a problematic contact allergen (van Wyk & Wink 2004).

Matricaria recutita has long held official recognition as a valuable medicine due to its antispasmodic, sedative, anti-inflammatory, carminative and analgesic properties. The flowers were highly valued for gastrointestinal dysfunction (bloating, feelings of fullness, mild spasmodic disturbances and sluggish bowels), to reduce intestinal pain or colic, to ease menstrual and nervous system distress (nervousness, hysteria) and as a gentle tonic for general debility. The British Pharmaceutical Codex of 1934 provides an official evaluation of the herb’s diverse attributes: Preparations of chamomile are used internally to improve the appetite and aid digestion … ‘Chamomile tea’ (1 in 20 of boiling water; dose 1 to 4 fluid ounces) is a domestic remedy for indigestion and may be used as a vehicle for other bitters. The flowers are sometimes employed externally in the form of a poultice. Used as a fomentation, chamomile is a popular remedy in the early stages of inflammation; a decoction of chamomile

The English Lawn Chamomile or Roman Chamomile (Anthemis nobilis), from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. and bruised poppy capsules is also used as a fomentation for dental abscesses; the decoction is applied inside the mouth and the marc [macerated herb residue] is applied as a poultice. The extract may be combined in pills with purgatives to diminish the tendency to griping.

Its topical anti-inflammatory properties continue to be considered extremely useful for mouth and throat disorders, rhinitis (nasal inflammation), toothache, earache, eczema, wound healing, headache and influenza (PDR for Herbal Medicines 2004; van Wyk & Wink 2004). A combination of apple pectin and Chamomile extract is effective for childhood diarrhoea, even in infants. Chamomile is also recommended for infant colic (de la Motte 1997; Weizman 1993). Recent investigations suggest the herb has benefits for preventing the raised blood sugar levels characteristic of diabetes (Cemek 2008; Kato 2008). Research has substantiated many of these recommendations. Chamomile essential oil has antibacterial properties against gram-positive bacteria, skin fungi (dermatomyces) and Candida – which is largely attributed to the high ɑ-bisabolol content.15


Extract of Chamomile, from British Pharmacopoeia, 1867.

Dried Chamomile flowers. (Courtesy Henna Sooq LLC, www.hennasooq.com)

Flower extracts have similar antimicrobial properties, as well as substantial anti-inflammatory, antispasmodic, gastroprotective and anti-ulcer activity, which also appears linked to the bisabolol component.16 Various other components in the herb have a supportive role: azulenes (anti-inflammatory); esters and lactones (anti-mycobacterial); chamazulene, flavonoids, umbelliferone (antifungal against Trichophyton); quercetin, luteolin, apigenin (antimicrobial); ɑ-bisabolol and spiroethers (antispasmodic). Chamomile, apigenin and quercetin have also shown significant anti-allergenic potential (Al-Hashem 2010; Cemek 2010; Bezerra 2009; Altern Med Rev 2008; McKay & Blumberg 2006). The azulenes have important pharmacological properties. In addition to its significant antiinflammatory activity, chamazulene (which is formed from matricine during the steam-distillation process) has antioxidant, antipyretic, anodyne, antiseptic, antispasmodic and vulnerary properties (Mann & Staba 1986). Guaiazulene is a similar anti15 The anti-fungal activity of the essential oil against Aspergillus also supports its use as an antifungal agent in stored food products (Tolouee 2010). 16 Chamomile oil has also shown activity against Helicobacter pylori, which supports its anti-ulcer activity (Shikov 2008).

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inflammatory compound with hepatoprotective and liver cell regenerative attributes (Kourounakis 1997a, 1997b). Certainly Chamomile possesses good antiallergic properties that make it useful for itching skin disorders (Chandrashekhar 2011; Lee 2010; Kobayashi 2005, 2003). Chamomile is one of the richest known natural sources of apigenin (840 mg/100 g), which would certainly exert an influence on the properties of the herbal remedy (McKay & Blumberg 2006). Apigenin possesses antispasmodic17, mild anxiolytic and sedative activity – as well as anticancer potential (chemopreventive and antimutagenic activity) (Anter 2011; Srivastava & Gupta 2009, 2007; Avallone 2000). Chamomile has a good clinical reputation as an anti-anxiety and insomnia remedy (Awad 2007; Zick 2011; Amsterdam 2009; Gould 1973). There is a particularly interesting study with regard to the use of Chamomile oil by over 8,000 women (applied to the skin or used as an inhalant) that found it was effective for reducing pain during labour and delivery (Burns 2000). During menopause, in combination with Angelica sinensis, it can help to to alleviate sleeplessness and regulate hot flushes18 (Kupfersztain 2003). In addition, the mild sedative properties may be useful for hyperactivity (ADHD), suggesting its use as part of a broader management strategy (Niederhofer 2009). Surprisingly, Chamomile extracts have antiviral properties against poliovirus and herpes virus – with clinical potential for use in Herpes genitalis (Koch 2008a, 2008b). The wound-healing attributes of Chamomile are effective for burn injuries and dermabrasion (tattoo removal) – and were even shown to be superior to corticosteroids for treating ulceration (Jarrahi 2010, 2008; Martins 2009; Nayak 2007; Glowania 1987). The herb’s potent anti-inflammatory, immune-supportive and healing attributes suggests its use to modify the side-effects of chemotherapy and radiation treatments, including the prevention of infections, mucositis (inflammation and ulceration of the gastrointestinal tract), stomatitis (mouth inflammation) and phlebitis (inflammation 17 10 mg of apigenin has shown antispasmodic activity equivalent to 1 mg of the opioid antispasmodic papaverine (Achterrath-Tuckermann 1980). 18 There may also be a direct hormonal influence of the herb. Experimental studies have suggested potential benefits for osteoporosis (Kassi 2004) – although this requires further clarification.

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of a vein) (Ghonime 2011; Pavesi 2011; Reis 2011; Mazokopakis 2005; Carl & Emrich 1991). Bisabololoxide A is a component that may provide a potentiating agent in combination with the anticancer drug 5-fluorouracil – which may reduce the drug dose and the risk of side-effects (Ogata-Ikeda 2011). Some studies have also suggested Chamomile may have neuroprotective potential against cerebral ischaemia, and anti-seizure effects (Ranpariya 2011; Chandrashekhar 2010; Heidari 2009) – as well as very interesting inhibitory effects on morphine dependence and withdrawal symptoms in animal studies (Gomaa 2003). However, it is possible that Chamomile may interact with warfarin and individuals on this drug should be cautious in its use (Segal & Pilote 2006) – although this may also be linked to an individual sensitivity reaction.

A Complex Essential Oil

Overall, around 120 constituents have been identified from German Chamomile flowers.19 The essential oil (yield 0.4–2%) is characterised by ɑ-bisabolol and chamazulene (50–65%). Other oil components include: ɑ-bisabolol oxides, cadinene, farnesene, furfural, spathulenol, proazulenes (matricarin and matricine), spiroethers and sesquiterpenes (anthecotulide) (Altern Med Rev 2008; McKay & Blumberg 2006). The following analysis is an indication of the proportions involved: ɑ-bisabolol (57%), trans,trans-farnesol (16%), cis-β-farnesene (7%), guaiazulene (4%), ɑ-cubebene (3%), ɑ-bisabolol oxide A (2%) and chamazulene (2%) (Tolouee 2010). Aromatic compounds with useful fragrance qualities of interest for perfumery purposes include farnesol20, an aromaenhancing agent that, in low Chamomile oil. (Courtesy amounts, acts to enhance Mountain Rose Herbs)

floral scents. Other fragrant components include borneol, a common additive in perfumed soaps and detergents. Bornyl acetate has similar characteristics, while ɑ-bisabolol is a perfume fixative. Nerolidol, which is present in Roman Chamomile, possesses a sweet Apple or Rose-like aroma that is a useful harmonising agent in scents (Mann & Staba 1986).

Dandelion: A Famed Liver Tonic

The ubiquitous Dandelion (Taraxacum officinale) is found throughout the southern temperate regions of Australia (New South Wales, Victoria, Tasmania and southwest Western Australia) – and there is even a record of its presence as far inland as Alice Springs. The different species can be difficult to tell apart and the name Taraxacum officinale has probably been applied, at some time or other, to the majority of Dandelions found in Australia.21 There are a couple of native species: Tataxacum aristum and T. cygnorum from Tasmania and Victoria – with the latter ranging to South Australia (but considered extinct in Western Australia). The Mountain Dandelion (Taraxacum aristum) is also found around the New South Wales–Victoria border. Naturalised species include the Russian Dandelion, Taraxacum kok-saghyz (Tasmania); T. squamulosum (Victoria); T. hepaticolor and T. khatoonae (South Australia). The common small golden-flowered Dandelion was an early herbal import. The perception of this plant as a commonplace weed, however, has possibly marred a wider appreciation of the remarkable potential of the remedy. Little is known about the medicinal properties of the native Australian species (Taraxacum aristum and T. cygnorum) – although the use of other members of the genus in Asian, Indian and European traditions shows enormous scope. European herbal wisdom has long recommended 19 Among those of importance are flavone glycosides (apigenin 7-glycoside and derivatives) and flavonoids (luteolin glucosides, quercetin glycosides, isorhamnetin) (around 8%), as well as other phenolics (cinnamic acid derivatives, mainly ferulic and caffeic acids). In addition, mucilage polysaccharides (10%) are present and small amounts of choline (0.3%) and coumarins (0.1%). 20 Isoprenoids such as farnesol and geraniol have also attracted interest for their anticancer potential. 21 There has been plenty of room for confusion. Estimates of the number of species in the genus range from 30 to 57 (with many microspecies), divided into nine sections. European herbal traditions use T. officinale, with the main suppliers being Yugoslavia, Romania, Hungary and Poland. Taraxacum platycarpum is used in Chinese medicine (Schulz 2006) – as is T. mongolicum (Yeung 1985).


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leaves in white wine, or the leaves chopped as pot herbs with a few alisanders22, and boiled in their broth, are very effectual. And whoever is drawing towards a consumption [tuberculosis, wasting], or an evil disposition of the whole body called cachexy [poor health, debility], by the use hereof for some time together shall find a wonderful help. It helpeth also to procure rest and sleep to bodies distempered by the heat of ague fits, or otherwise; the distilled water is effectual to drink in pestilential fevers, and to wash the sores.

While this may appear to be overstating the case for Dandelion as a paragon of multiple virtues, recent research into its antibacterial, antiviral, immunomodulatory, anti-inflammatory and potential anticancer activity have to agree that this is a rather remarkable herbal remedy.

Dandelion, from Franz Eugen Köhler, Köhler’s MedizinalPflanzen, 1897.

Dandelion as a diuretic and cleansing liver tonic with detoxicant properties considered useful for blood purification, which led to its use for clearing skin blemishes. The herb also had a circulatory supportive effect, antacid properties, and an ability to restore gastric function following episodes of severe emesis. The latter could possibly be linked to the fact that Dandelion is rich in minerals (particularly potassium, calcium, sodium) and is an excellent source of vitamins B, C and E (Altern Med Rev 1999). Studies also suggest a cholinergic stimulatory effect with benefits for digestive function (Jin 2011). Nicholas Culpeper (1653) wrote that Dandelion had: an opening and cleansing quality, and therefore is very effectual for the obstructions of the liver, gall, and spleen, and the diseases that arise from them, as the jaundice and hypochondriac; it openeth the passages of the urine both in young and old; powerfully cleanseth imposthumes [abscess] and inward ulcers in the urinary passages, and by its drying and temperate quality doth afterwards heal them; for which purpose the decoction of the roots or

Taraxacum succus. (Courtesy The Apothecary, Cairns)

Taraxacum, from the Extra Pharmacopoeia Martindale, 1941. 22 Smyrnium olusatrum, a plant of the Umbelliferae, with a celery/parsley type of flavour.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary taken one of two tablespoonfuls two or three times daily – Cooley’s Practical Receipts.

The roots were considered to be in best condition for harvest in early winter. He concluded: ‘A good demand for properly-dried roots, free from earth and any foreign substances, always exists, and considering the little trouble of cultivation and harvesting, the price obtained may almost be looked up on as clear profit.’

Taraxacum, from the British Pharmaceutical Codex, 1934,

In 1893, T Phillips-Gibson noted that Dandelion ‘has been introduced and succeeds well in many parts of Australia’, although he does caution about its propensity to become a troublesome weed once established. With regard to its practical use he comments: There are several preparations of dandelion weed used in medicine, the British Pharmacopoeia recognising a decoction, extracts from both the fresh and dried roots, as well as an extract of the juice in spirit. The decoction is made by boiling 1 oz. of the root in a covered vessel, and, after being strained, the liquid made up to a pint by adding more water; the dose being two to four teaspoonfuls. The extract is more difficult to prepare. It is made as follows:- The fresh root is bruised, and the juice allowed to settle; the liquid is then heated to 212deg:F, this heat maintained for ten minutes, and the extract afterwards evaporated till it is thick enough to be made into pills. A good preparation for domestic use is made with 4 oz. of the fresh roots in 1½ pints of water, and boiling down to 1 pint, and then straining. This can be

Dandelion root, from Alice Henkel, ‘Weeds Used in Medicine’, US Department of Agriculture, Farmer’s Bulletin, 1917. The use of dandelion extracts as a flavouring for various food products (alcohol, soft drinks, desserts, confectionary, baked goods, puddings, cheese), or roasted as a coffee substitute, appears to have diverse unappreciated benefits in light of recent research on the medicinal properties of the herb.

Clinically, Dandelion has significant diuretic effects with the potential to replenish potassium and magnesium levels (leaf content: 42.5 mg/kg and 2.5 mg/kg, respectively). This is important as hypokalaemia (low potassium) and hypomagnesia (low magnesium) are serious side-effects of conventional diuretics. Some studies have shown that extracts obtained from the herb were consistently stronger in activity than root extracts (Clare 2009; Altern Med Rev 1999; Racz-Kotilla 1974). Dandelion contains a number of other components (primarily


The most abundant phenolic compounds in Dandelion flowers and leaves are hydroxycinnamic acid derivatives – notably chlorogenic, dicaffeoyltartaric (chicoric) and monocaffeoyltartaric acids (Schutz 2006). Extracts of Dandelion flowers have significant antioxidant properties which are linked to these phenolic components. Coumarins (aesculin, cichoriin) and numerous flavonoids are also present (Hu & Kitts 2005; Williams 1996).

flavonoids) of pharmacological interest23 with diuretic attributes: caffeic acid (anti-aggregant, antiinflammatory, antioxidant, anxiolytic), chlorogenic acid (anti-inflammatory, antioxidant, cardioprotective), isoquercitrin (anti-inflammatory, antioxidant, hypotensive) and luteolin24 (anti-inflammatory, antioxidant, hypocholesterolemic, vasodilator), as well as mannitol (anti-inflammatory, antioxidant) (Duke 2011). 23 For a comprehensive appraisal of the chemical components of the genus see the review by Katrin Schutz (2006). 24 The anti-inflammatory properties of luteolin appear to be supported and enhanced by chicoric acid in the herb (Park 2011b).

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Chicory (under the old name Succory), Cichorium intybus, was known to herbalists of old as a plant for healing the liver and the lungs. Nicholas Culpeper (1653) asserted that ‘A handful of the leaves or roots, boild in wine or water, and a draught drunk fasting, driveth forth choleric and phlegmatic humours, openeth obstructions of the liver, gall and spleen; cureth the yellow jaundice, the heat of the reins [kidneys], and of the urine.’ The wine-based decoction was excellent for fevers – while the seed powder could help prevent a ‘fit of the ague’. The leaf poultice (or a wash with vinegar) could remedy all forms of skin problems (pustules, wheals, pimples, pestiferous sores, inflammation), conjunctivitis, allay ‘swellings’ and St Anthony’s fire. The ground root has retained its fame as a liver detoxicant. It has long been used by the French as a coffee adulterant, to counteract the stimulating effect of caffeine (Leyel 1937) – although more recent practices utilise the root as a coffee alternative.

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as an anti-diabetic remedy with extracts showing anti-hyperglycaemic activity, as well as effects on metabolism that suggest benefits for diabetes, atherosclerosis and obesity (Goksu 201; RodriguezFragoso 2008; Onal 2005; Petlevski 2003, 2001; Altern Med Rev 1999): • Root extracts have blood sugar-regulating properties that may be linked to a high content of inulin, a polysaccharide fibre that helps prevent blood sugar fluctuations (Altern Med Rev 1999). • Oligofructans from the herb may have a potential role for maintaining colonic bifidobacteria levels (Trojanova 2004). Root and leaf extracts have cholesterol• lowering (hypolipidaemic) properties with antiatherosclerosis potential (Choi 2010). • Extracts have pancreatic lipase (the key enzyme for dietary fat digestion) activity, which suggests that the herb may be of use as an anti-obesity agent (Zhang 2008). • In addition, preliminary investigations of Dandelion’s anti-inflammatory effects suggest a protective role in pancreatitis (Seo 2005). Dandelion weed, showing the toothed leaves. The genus name originates from the French dent-de-lion, from a fancied resemblance to the ‘tooth of the lion’.

The traditional use of Dandelion as a hepatoprotective and cholagogue (increasing the flow of bile) is supported by a number of studies. It can protect against alcohol and various forms of chemical injury to the liver, as well as enhancing its regenerative properties (Park 2011a, 2010a, 2010b; Domitrovic 2010; Mahesh 2010; You 2010). It should come as no surprise that the herb has significant antiinflammatory and antioxidant properties, which would be valuable in a number of different conditions including the prevention of lung tissue injury (Liu 2010). Studies also suggest a protective effect on the central nervous system (Kim 2000). Flower and root extracts (Taraxacum officinale, T. platycarpum) have been reported to possess excellent anti-oedema properties. Root extracts attracted additional interest when their activity was shown to be significantly improved in combination with the anti-inflammatory drug indomethacin (Hagymasi 2000a, 2000b; Yasukawa 1998, 1996; Tita 1993; Mascolo 1987). Dandelion has had an interesting reputation

A Traditional Anticancer Herb Chinese Dandelion

Chinese Dandelion (dried flower for medicinal use, pictured) is sourced from Taraxacum mongolicum, T. officinale and T. sinicum.


The fact that other Taraxacum species have equally interesting medicinal potential is evident by the use of the Chinese Dandelion (T. mongolicum) as a cleansing, anti-inflammatory, antibacterial and healing agent. Recommendation as a toxinneutralising remedy has seen it employed in ‘heat’ conditions – abscesses, sores and nodules. It is particularly useful for dissipating ‘hard nodules’, as well as for treating breast or intestinal abscesses. Additionally, the Chinese Dandelion can be used as a lactogen to promote lactation25 (Bensky & Gamble 1986; Yeung 1985). The herb has been highly regarded for soothing ophthalmic problems characterised by redness, swelling and pain of the eyes (conjunctivitis). Extracts have shown activity against a wide range of bacteria – including the causative agents of gastrointestinal and respiratory disorders: Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Shigella spp., Neisseria meningitidis, Corynebacterium diphtheriae, Mycobacterium tuberculosis (Bensky & Gamble 1986, Yeung 1985). Taraxacum formosanum has similar antibacterial effects against Streptococcus aureus and Mycobacterium tuberculosis, as well as Leptospira (Leu 2005). The use of Chinese Dandelion as an antibacterial agent is well established in traditional herbal practice. However, the high mineral content of this herb has the potential to

Acne formula from Cathay Herbal which has Chinese Dandelion as a major ingredient. (Courtesy Cathay Herbal) 25 While Dandelion is not normally thought of as having hormonal properties, there are a couple of studies that have suggested effects on oestrogen receptors and an anti-fertility effect in male rats (Tahtamouni 2011; Zhi 2007).

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The white-flowering Japanese Dandelion (Taraxacum albidum) is a cross between T. coreanum and T. japonicum. (Courtesy Mokimisato, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

limit the absorption of quinoline antibiotics (e.g. ciprofloxacin). Therefore, it would be advisable to ensure that the herb and this type of drug are not taken at the same time (Zhu 1999). Interestingly, Chinese Dandelion has a good practical anticancer reputation and is traditionally included in compound prescriptions for treating leukaemia, gastric cancer, and cancer of the breast or cervix (Menghini 2010; Sigstedt 2008; Koo 2004; Takasaki 1999a, 1999b; Chang 1992): • In breast cancer treatments Chinese Dandelion was used in combination with Snakegourd fruit (Trichosanthes kirilowii), Olibanum (Frankincense, Boswellia carterii), Myrrh (Commiphora myrrha), Gan Cao root (Chinese Liquorice, Glycyrrhiza uralensis) and Tangerine or Mandarin Orange leaves (Citrus reticulata) – the herbs being mixed with wine before being taken. • Chinese Dandelion has also been used for treating cancers of the nasopharyngeal region and mouth (gingival or hard palate). In the Renewed Compilation of Mei’s Experienced Recipes some specific details are provided: ‘Herba Taraxaci, with only one stock about 0.3 meter high, two flowers and a root as large as a human fist, cures dysphagia [difficulty swallowing] with

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a miraculous effect if pounded and taken with wine’ (Chang 1992). • The strong antioxidant and anti-inflammatory properties of Dandelion (T. officinale and T. japonicum) may play a role in its immune supportive and anti-tumour activity (Koh 2010; Jeoan 2008; Kim 1999, 1998). • In addition, herb extracts have demonstrated activity against liver cancer cells, while root extracts showed anti-leukaemic properties – which may be linked to a number of components with anticancer potential – taraxinic acid26, taraxasterol and taraxerol (Ovadje 2011; Koo 2004; Choi 2002).

Of these, the Chinese Dandelion root exhibited antimelanoma properties associated with its lupeol content (Hata 2000). Luteolin and luteolin 7-glucoside from Taraxacum officinale flowers contributed to its significant antioxidant and cytotoxic properties (Hu & Kitts 2005, 2003). Investigations have also found that Taraxacum mongolicum had anti-inflammatory and immune-modulating actions, and antiviral activity against the Herpes simplex virus (Kim 2011; Luo 1993; Zheng 1990).

Chinese Dandelion herb.

The anticancer potential of diverse natural products as anti-melanoma agents has been a recent topic of considerable interest. A Japanese investigation evaluating a wide variety of natural products (25 types of seaweed, 26 mushrooms, and extracts of 49 wild plants) found that extracts of all the herbs belonging to the Compositae (now Asteraceae) family, subfamily Cichorioideae, had an effect on melanoma cell lines. 26 This compound is prevalent in the genus. For the purposes of this study it was isolated from a Korean species, T. coreanum, which is utilised similarly to the common Dandelion as an anti-inflammatory and diuretic remedy (Choi 2002)

Taraxacum platycarpum has been traditionally utilised as an anti-inflammatory for gastrointestinal disorders (ulcers and colitis). It contains a polysaccharide with immune potentiation and anti-tumour activity, as well as an anti-allergic component27 (desacetylmatricarin) and an anticoagulant agent (Yun 2002; Cheong 1998; Jeong 1991). Similar immunomodulatory and anti-tumour activities have been reported for Taraxacum officinale (Altern Med Rev 1999). (Upper image courtesy Tsutomu Otsuka, flickr; lower image courtesy Hatimaki, flickr) 27 It should be noted that there are reports of contact dermatitis associated with Dandelion – however, these reports only appear to be linked to contact with the plant pollen, and not the herb itself.


Dandelions for Rubber and Gas The fact that synthetic rubber is a petroleumbased product that is becoming progressively more expensive has sent researchers looking for alternative natural rubber-yielding plants. The cultivation of the classic rubber resource, Hevea brasiliensis, is limited by a form of leaf-blight (due to Microcyclus ulei) and the fact that the crop takes a long time to reach maturity. The establishment of plantations can also have a significant negative environmental impact. Alternatives are Guayule (Parthenium argentatum), which is a fairly slowgrowing desert plant, and the Russian Dandelion (Taraxacum kok-saghyz), the sap of which can produce good quality rubber (Buranov & Elmuradov 2009; The Economist 2009; Wahler 2009; van Beilen & Poirier 2007). Interestingly, the use of Russian Dandelion as a rubber resource was suggested during World War II. A review of its potential was produced by WG Whaley and JS Bowen in 1947 for the US Department of Agriculture – although the processing costs were considered prohibitive at the time. This species, like the Common Dandelion, is also an inulin resource that can be turned into bioethanol using fermentation processes – thereby leading to the suggestion of its use as a biogas fuel resource (Van Beilen & Poirier 2007).

The Russian dandelion (Taraxacum kok-saghyz) was discovered in Kazakhstan in 1932 by USSR scientists searching for a domestic rubber resource. It was subsequently cultivated as a crop and used for tyre manufacture by Russia and Germany during World War II. The plant was introduced into Tasmania by visiting American forces at this time. (Image courtesy Ford Motor Co., USDA publication)

Marigolds: Treasure in the Garden

Calendula officinalis. (Images courtesy Herbert Zell)

Achenes (seed-containing fruit) of Taraxacum koksaghyz. (Tracey Slotter, USDA; provided by ARS Systematic Botany and Mycology Laboratory, Yugoslavia)

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‘Marigold’ commonly refers to species of Tagetes and Calendula – both of which have excellent reputations as wound-healing and febrifugal agents. Calendula, which is a familiar garden escapee across the world, has its origins in the Mediterranean and the Atlantic islands, while Tagetes is native to South America and Mexico. The edible leaves and flowers of both herbs can be used as salad ingredients and are popular herbal teas. Powdered Marigold flowers also provide a colouring and seasoning in a similar manner to Saffron. The active dye flavonoids from Calendula officinalis (patulitrin, patuletin) are only found in the blossoms during and after flowering, and cultivation conditions similar to the Mediterranean climate type are important for their production (Guinot 2008). For centuries Calendula has maintained an impressive therapeutic reputation in Europe. Its

The seed-containing achenes of Calendula make an interesting display when the plant is in fruit. The bloom is composed of individual florets that result in this seed head configuration. (Images courtesy Herbert Zell)

efficacy, similar to that of many wound-healing herbal medicines, has been based on the fresh plant. The simplest way of using it is to apply the golden flowers or pulped plant as a dressing, although a tincture, with good keeping qualities, was easily prepared. Dr Dorothy Shepherd, who wrote of her extensive clinical experience with herbal and homoeopathic medicines in A Physician’s Posy, recommended a tincture based on the use of half-opened buds or newly-opened flowers (with gummy end-shoots), pounded and macerated in 50 per cent alcohol. The mixture was regularly shaken (several times daily) for three weeks. It was then filtered and stored for use. A fresh juice or succus could be made by pulping the whole plant (including pre-soaked roots), which provided a lotion for immediate use, or alcohol could be added as a preservative (Shepherd 1969). Dr Shepherd’s praise of Calendula was effusive: ‘The Marigold is a wonderful flower, a magic herb; looking at it, it raises one’s spirits, gives one hope … its uses are manifold. It provides the healing touch of nature and prevents the spread of disease, the spread of sepsis – a wonderful mission.’ She considered it an essential part of the household medicine cabinet: ‘It is the best herbal wound dressing and antiseptic that I know. Alack and alas! that so few, even keen homoeopaths, appreciate its value as such. I worked for years in various homoeopathic hospitals and never saw it used; we used the same lotions, tinctures and dressings as the orthodox hospitals. And yet there were a few valiant spirits who prescribed Calendula in wound treatment. Such a one was Dr. Carleton, who used it in peace time in his hospital in America as a dressing in all kinds of surgical work and for different types of operations.’ She mentions his use of the tincture (dilution 1:25) for amputation procedures, trephining the skull, gum swelling following dental work, haemorrhage after circumcision, and ‘mopping out the inside of the abdominal cavity after operations for abdominal tumours and ovarian cysts’. Calendula is a specific for clean cuts, incised wounds, and painful breaks in the skin surface such as gum ulcerations, cracks inside the nostrils or on the heel of the foot. It has been highly regarded as a healing agent in maternity cases, applied to wounds and incisions of the vulva and perineum. Healing was said to progress so well that it took ‘place in less than half the usual time’.


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Calendula tincture is useful for numerous types of skin problems and infections (bruising, ulceration, boils) as well as wounds (to stop bleeding and promote healing). (Image courtesy Dr. Reckeweg & Co., Bensheim, Germany)

Calendula officinalis. (Courtesy Teun Spaans, Wikimedia Commons)

While the herb was preferentially employed to prevent infection, Dr Shepherd also mentioned its use for infected wounds, including ulceration or septic gums: ‘Calendula officinalis is not an antiseptic in the true meaning of the word; but it is a fact that germs do not thrive in its presence, it inhibits their growth and even if wounds are already badly infected I have seen offensive, purulent discharge become clear and sweet-smelling in a day or two. Calendula is wonderfully soothing as an external application, it neither destroys nor irritates any new epithelial cells which are forming; it rather stimulates their growth.’ Additionally, Calendula was a highly effective styptic useful for bleeding cuts, wounds, grazes, and even haemorrhagic injuries. Dr Shepherd lamented the lack of commitment regarding the recognition of herbal medicines such as Calendula: ‘I wish more lay people would have greater conviction in their faith, and boldly admit what has cured them, and invite their doctors to experiment at first with such simple remedies as Calendula and Arnica, and later go into it more thoroughly and scientifically. We should get somewhere!’ Close to half a century later there appears to be some good news in this respect. Certainly she would have been impressed with recent innovations suggesting the use of Calendula-impregnated nanofibres as wound dressings (Vargas 2010).

Calendula: Favoured Herb of the Ancients Edward Hamilton (1852) provides the following review of Calendula, quoting

Calendula drawing from Edward Hamilton, Flora Homoeopathica: Illustrations and descriptions of the Medicinal Plants used as Homoeopathic Remedies, Leath & Ross, St Paul’s Churchyard, Oxford St, London, 1852.

numerous authorities. Of particular interest is its reputation for painful conditions and in the treatment of cancerous growths: The ancients considered the Calendula a deobstruent remedy, exerting a great influence on the circulation. Dioscorides recommends it in cancer; and Fuchsius (Hist. Stirp., 1546) prescribed the juice of it against toothache … Gerarde, also, in describing its virtues

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary remarks, ‘that the flowers and leaves of Marigold being distilled, and the water dropped into red and watery eyes, ceaseth the inflammation and taketh away the pains.’ Calendula was formerly in much request as a medicine, and was used more especially in carcinoma and scirrhus [a hard cancerous growth]; according to Westring, with great effect in the third stage, particularly in diminishing the pain, and rendering the pus less corroding; but on further experiment by others, the same effects were not produced28, and therefore it was thrown aside. It was also used in chlorosis [anaemia], hysteria, epilepsy, jaundice, and some kinds of dropsy. Schneider found it of great efficacy as a lotion to fresh wounds, inducing union by the first intention. Zorn considered Calendula of great service in throwing out the eruption of measles and small-pox; and as a topical application to stop the bleeding in haemorrhoides fluentes. It was a favourite remedy with Boerhaave, who employed it in uterine diseases, in diseases of the kidney, and jaundice. Its chief use, however, was for cancer, and it was the principal ingredient in the famous Rust Pill, which consisted of oxide of iron, colewort, and extract of Marigold. W. Carter found the extract of Calendula of great assistance in obstinate vomiting; and De Camp, in a case of cardialgia [cardiac pain], where all medicines, etc., were vomited up, owing to a great irritability of the stomach. Muhrbeck used the extract of Marigold, in chronic vomiting, with great success, in a case where violent pains were felt at the same time in the region of the uterus; it was remarked that these pains increased when the dose exceeded thirty-four grains in the twenty-four hours. It is interesting to note that Elgafaki states that violent vomiting ensues after taking four drachms of the juice of Marigold. Dr. Stein extols the efficacy of this plant in cancer of the skin; he prepares the juice from the green plant and its blossoms, and makes an ointment with butter and charcoal, which is applied to the ulcer. 28 Dr Shepherd emphasised that the quality of the preparation was of paramount importance and could well account for variation in the efficacy of the remedy.

The skin rejuvenation, anti-inflammatory and hydrating properties of Calendula creams have made the herb popular for cosmetic purposes (Akhtar 2011). Recent studies evaluating effective preparations for clinical use found a Calendula cream using a

hydrophilic base and a complex emulsifier was the best choice for preventing microbial contamination. This combination maintained the integrity of the carotenoids, polyphenols and flavonoids that were identified as the primary antioxidant components. Calendula oil prepared with saturated oils is also very stable with regard to carotenoid content (Bernatoniene 2011; Bezbradica 2005). Calendula leaf and flower poultices or decoctions have been well regarded as anti-cancer remedies employed for treating skin growths (warts, cancer), breast and uterine growths, ‘glandular indurations’ and cancerous ulcers. Investigations showing antiinflammatory, antioxidant, immune-stimulant, antimetastatic, cytotoxic and anti-tumour promotion properties certainly lend significant support to these recommendations. Calendula’s protective effects on skin tissue may be equally useful against the development of skin cancer (Preethi 2010, 2009, 2008, 2006; Fonseca 2011, 2010a, 2010b; Herold 2003; Jimenez-Medina 2006; Ukiya 2006; Varlijen 1989; Boucard-Maitre 1988). In addition, initial studies have suggested that Calendula extracts can protect against cellular injury associated with cigarette smoke exposure (Ozkol 2011). Safety assessments agree on the non-toxic properties of Calendula and it is now widely available in creams, oils and lotions for easing inflammatory skin disorders. However, there is a specific caution for individuals who are sensitive to plants of the Asteraceae family as they can suffer allergic dermatitis from exposure to the herb. It is always wise to be aware of such sensitivities (Andres 2009; Reider 2001). Although a number of components such as coumarins (e.g. herniarin; Paulsen 2010) have been implicated in allergic reactions, bisabolol is one of the more common allergens (Russell & Jacob 2010). A number of studies have confirmed the antimicrobial properties of Calendula extracts29 against both gram-positive and gram-negative bacteria. Water-based extracts with effective antibacterial properties had particularly good activity against Staphylococcus aureus, as well as Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. Leaf extracts have similar antibacterial properties, showing the 29 Oleanolic acid from Calendula flowers has also shown antibacterial activity against gram-positive bacteria, while oleanolic acid glycoside had antiparasitic properties against the larva of an intestinal parasitic nematode (Heligmosomoides polygyrus) (Szakiel 2008).


greatest activity against Klebsiella pneumoniae (Bissa & Bohra 2011; Roopashree 2008; Dumenil 1980). Other studies have shown activity against the gastric pathogen Campylobacter jejuni, which supports its use as an antidiarrhoeal agent, particularly in childhood diarrhoeal disorders (Cwikla 2010). The antispasmodic properties of flower extracts may also help in gastrointestinal disorders (Bashir 2006). The reputation of Calendula oil as a healing agent for mouth problems (sore gums, ulceration, cheilitis, dental problems) is equally well supported by studies showing activity against a range of periodontal bacteria. However, the type of solvent utilised and the method of preparation are highly influential with regard to the efficacy of the remedy (Machado 2010; Roveroni-Favaretto 2009; Iauk 2003; Modesto 2000). The antifungal activity of Calendula essential oil extends to diverse Candida species (C. albicans, C. dubliniensis, C. guilliermondii, C. parapsilosis, C. glabrata, C. krusei, C. tropicalis) and to Rhodotorula spp., indicating good potential for use in yeast infections including vaginal candidiasis30 (Gazim 2008a). Calendula oil’s antibacterial and analgesic properties suggest that it could be useful for ear infections (otitis media31) (Saify 2000; Shaparenko 1979). Calendula’s excellent anti-inflammatory, woundrepair and burn-healing attributes have been verified by numerous studies – with potential for use in serious conditions such as venous leg ulcers, or to prevent tissue damage due to radiation therapy following breast cancer surgery (Parente 2011; Preethi & Kuttan 2009a, 2008; Chandran & Kuttan 2008; Leach 2008; Pommier 2004; Duran 2005; Amirghofran 2000; Dietz 1998; Lievre1992; Rao 1991; Klouchek-Popova 1982). There are also indications of hepatoprotective and renoprotective potential, as well as anticancer activity against liver cancer (Manal 2010; Preethi & Kuttan 2009b; Ali & Khan 2006; Gupta & Misra 2006; Rusu 2005; Cordova 2002; Lin 2002). The anti-inflammatory and healing attributes of Calendula are also of interest for gastrointestinal disorders such as colitis and ulceration. Some of the active components were identified as calendasaponins32 30 Calendula has been recommended in a douche preparation (with Thuja, Gotu Kola, Yarrow, propolis, German Chamomile, and Roman Chamomile) for the treatment of cervical dysplasia. See Katolen Yardley (2001) for full details of the treatment protocol. 31 A clinically effective formulation for the relief of ear pain contained a combination of Garlic, Verbascum thapsus, Calendula officinalis flowers, Hypericum perfoliatum, Lavender and vitamin E in olive oil (Sarrell 2001).

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Field Marigold (Calendula arvensis). The Field Marigold is widespread in southeastern Australia, ranging to Tasmania and South Australia. Calendula flower extracts possess antiviral activity against HIV, Herpes simplex and influenza viruses with interesting clinical potential (Kalvatchev 1997; Bogdanova 1970). Triterpene saponins from Calendula arvensis have demonstrated antiviral activity (De Thommasi 1991, 1990). (Image courtesy Zachi Evernor, flickr)

with gastroprotective and hypoglycaemic properties (Yoshikawa 2001; Borrelli 2000; Chakurski 1981, 1980) – while Calendula polysaccharides had a protective mucilaginous effect on irritated mucous membranes. Some polysaccharides (heteroglycans) also have immune-stimulating properties (Schmidgall 2000). Another study has suggested that Calendula could have cardioprotective properties against the ischaemic injury that accompanies a heart attack (Ray 2010). 32 Saponins have been isolated with anti-inflammatory, haemolytic and molluscicidal activity (Mostafa & Tantawy 2000; Helaly 1999; Chemli 1990). Triterpene glycosides such as faradiol have shown significant antioedemic activity comparable to indomethacin. Faradiol esters and psitaraxasterol possess similar activity, albeit less potent. Another study isolated a faradiol ester in Calendula flowers with significant anti-inflammatory activity. The triterpene calenduloside B (isolated from Calendula roots) also has effective anti-ulcer properties (Marukami 2001; Zitterl-Eglseer 2001, 1997; Della-Loggia 1991, 1990; Chakurski 1981a, 1981b; Shipochliev 1981; Iatsyno 1978).

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The golden-flowered Calendula is considered to have a wide variety of therapeutic properties: wound healing, analgesic, antispasmodic, astringent, antimicrobial, emmenagogue, carminative, laxative and anthelmintic. The herb has been popularly utilised as a febrifuge in conditions as diverse as cholera, typhus, colds, and influenza. Investigations have identified various compounds with a range pharmacological Calendula: a quality tincture. of (Courtesy The Apothecary, properties that include anti-inflammatory Cairns) (anti-phlogistic), antiulcerative, wound-healing, sedative, and uterotonic activity. The flower oil (yield 0.1% essential oil33 from dried flowers) primarily contains cadinene (d-cadinene: 18-55.2%, y-cadinene: 9–25%) and ɑ-cadinol (20%), epi-ɑ-muurol (12%), ɑ-muurolene (5.6%), with smaller amounts (2–3%) of viridiflorol, ɑ-calacorene, ledene, β-ionine and y-muurolene (Gazim 2008b). 33 The Calendula oil often used for healing purposes is an infused flower oil. This analysis refers to the steam-distilled essential oil.

Decontamination: New Uses for Old Herbs Calendula alata has been studied for the phytoremediation of cesium and lead. Plants grown in contaminated hydroponic solutions, while being reasonably effective at reducing cesium levels (41–52% removal), were much more efficient at binding lead (95–99%) (Borghei 2011). Chenopodium album and Amaranthus chlorostachys were other effective candidates for cesium phytoremediation (Moogouel 2011). A number of species of Dandelion also appear to have lead and cadmium accumulation properties that may be useful for environmental

Calendula alata is native to western Asia (Iran, Iraq) and Russia, Pakistan and India.

remediation (Wei 2010; Pichtel 2000). French Marigold (Tagetes patula) has similar cadmium accumulation and tolerance attributes (Liu 2011) – an affinity that can be enhanced by treatment with EDTA (ethylene diamine tetra acetic acid), which will also increase the chelation of zinc, copper and iron by this plant (Sinhal 2010). Conversely, wild herbs should not be harvested for medicinal use from contaminated


sites, including roadside verges, car parking sites, industrial areas or rubbish dumps. French Marigold also has effective remediation properties for soils contaminated with the highly carcinogenic coal tar compound, benzo[a]pyrene (Sun 2011). In the eighteenth century this was the compound responsible for scrotal cancer in chimney sweeps, and in the nineteenth century was associated with the development of skin cancer among fuel industry workers. High levels are found in exhaust fumes (especially diesel), cigarette smoke, barbecue charcoal, and charbroiled foods. The potent dietary antioxidant activity of vitamin C may well have antidotal effects against this carcinogen. In addition, intriguing environmental attributes have been discovered for herbal dye wastes. An Indian study of the wastewater from Aztec Marigold (Tagetes erecta) that compared it to the wastewater from a number of other dye plants (Hibiscus rosa-sinensis, Rosa rugosa and Canna indica) revealed arsenic detoxicant (biosorbent) properties of significance (85–98% arsenic removal) – which suggests it has valuable applications for environmental remediation, with potential for use in local projects (Nigram 2012). Rice husks have similar attributes (Ranjan 2009) – as does a stem powder from Acacia nilotica (Baiq 2010).

Tagetes erecta. (Courtesy Kurt Stüber, CC-by-SA 3.0 Unported)

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Tagetes: American Marigolds

Marigold flower infusions have long been a popular stimulant with diuretic, stomachic and carminative effects. A number of species are commonly utilised medicinally, primarily Tagetes erecta, T. lucida, T. minuta, T. patula and T. filifolia.

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The genus Tagetes from North and South America has provided some versatile, highly valued remedies, that are used in a very similar manner to Calendula. These herbs have been adopted into garden cultivation across the world – indeed, the Aztec Marigold (Tagetes erecta) is also known as ‘African Marigold’, while ‘French Marigold’ refers to T. patula. A tea made from the juice or the ground leaves of Aztec Marigold has been a common appetiser, while the flower juice was widely recommended as a blood purification agent (Neher 1968). In South America Tagetes erecta has been a popular tonic stimulant, and a useful diaphoretic agent to induce perspiration in fevers. It has been utilised in treatments for body pain, sore throat, influenza, rashes, gastrointestinal distress (diarrhoea, stomachache), heart attack, arthritis – and against the ‘evil eye’ (Alonso-Castro 2012). An infusion of three flowers steeped in a cup of boiling water for 10 minutes was a simple tea preparation – or the whole plant could be decocted in two gallons of water for 10 minutes and added to a bath for children and infants with influenza, fevers or colds, and to ease general malaise, colic or diarrhoea. The decoction provided an equally useful wash for wounds, sores, abscesses and

inflammatory skin problems. Additionally, the herb has been a popular aid for gastrointestinal function (infant colic, gastric pains, flatulence), and used as a headache remedy (Arvigo & Balick 1993). Brazilian and Mexican traditions have used the decoction or infusion of Aztec Marigold extensively for respiratory problems, particularly bronchitis and lung disorders. The hot leaf poultice was applied to boils and carbuncles, or the flower juice taken as a remedy for piles (haemorrhoids). In Brazil the roots were also recommended as a laxative, while a Mexican

Mexican Tarragon (Tagetes lucida) is a good tarragon substitute in cooking. Methyl chavicol is present in extremely high amounts (95–97%) in the distilled oil of the fresh herb and imparts an anise aroma to the plant (Ciccio 2004). An analysis of the coumarin components found they had a broad spectrum of antibacterial activity, notably against gram-negative bacteria – as well as good antifungal properties. The activity of a number of coumarins (including esculetin and scoparone) against the cholera bacteria (Vibrio cholerae), which is transmitted in contaminated water supplies, was of particular interest. Certainly this tends to support the traditional use of the herb as a cure for gastrointestinal diseases. In addition, the herb has been recommended ‘to calm mental agitation’, as a hangover cure, and ‘to diminish the harsh manifestations of smoking Turkish tobaccos’ (Cespedes 2006). The herb decoction has also shown antidepressant properties (Gabriela 2012).


anti-malarial treatment employed an ointment (based on the juice and leaves) externally to prevent chills. In addition, the herb has been incorporated into diverse remedies for liver problems, for use as a muscle relaxant, and even as an aphrodisiac potion (Neher 1968). Tagetes patula, which is naturalised in some regions of southeastern Australia, has been similarly recommended in the folk traditions of Mexico and South America as a diuretic, stomachic, nervine and carmative remedy. It has been equally valued in the Philippines, where the flower-based infusion was taken to relieve the discomfort of colic and intestinal gas. In Colombia, Tagetes patula flower tea was used as an eyewash, while in India the leaf juice of Tagetes erecta provided eyedrops. Both species have been utilised as infusions or rubs for easing rheumatic or arthritic pain – with studies verifying their antioxidant, antiinflammatory, analgesic and anti-arthritic properties (Faizi 2011a; Bashir & Gilani 2008; Kasahara 2002; Neher 1968). Studies have also shown Tagetes patula root extracts have hypotensive activity, which was attributed to citric and malic acids, while the pyridine hydrochloride component had a hypertensive effect (Saleem 2004). Interestingly, Tagetes patula and T. erecta earned a good reputation for the treatment of bunions and corns. They have been considered particularly useful for verruca (warts), fungal nail infections and a condition known as hallux abducto valgus (a deviation of the big toe toward the outer side of the foot). Verruca lesions are characterised by a thickened and heavy callus that causes irritation, inflammation and pain. Clinical studies have shown that the remedy had an analgesic effect and was effective for reducing the size of the growth (Khan 1996a, 1996b). The essential oils of Tagetes minuta and T. patula flowers have significant antifungal properties. The latter contains piperitone (24.7%) and piperitenone (23%), as the main components – with smaller amounts of terpinolene (8%), dihydro tagetone (4.9%), cis-tagetone (4.6%), limonene (4.5%) and allo-ocimene (3.7%) (Romagnoli 2005; Bii 2000). Herb extracts have equally valuable antifungal properties, with a thiophene constituent (ɑ-terthienyl) possessing substantial activity against the dermatophytes associated with skin infections (Mares 2004; Romagnoli 1994). Tagetes minuta flower oil also possesses antifungal properties.

Marigold Carotenoids

Tagetes erecta.

Aztec, Mexican or African Marigold (Tagetes erecta) has considerable commercial value as a carotenoid resource. It provides a yellow dye suitable for use as a food colouring, particularly for butter and cheese.34 Xanthophylls and carotenoids from the flowers have demonstrated antimutagenic, antioxidant, and anticarcinogenic properties that enhance its usefulness as a food additive (Breithaupt 2002; Brazana 2001; Gonzalez de Mejia 1997; Chew 1996; Neher 1968). Lutein (a xanthophyll pigment) is of particular interest due to its significant therapeutic potential, notably as an antioxidant, immune stimulant and anticancer agent. In particular, lutein has shown protective potential in colon and breast cancer cells. Lutein, as well as another yellow carotenoid pigment, zeaxanthin, accumulate in the retina of the eye and have been linked to a protective effect against age-related macular degeneration and cataracts. Both conditions can result in blindness. The lutein in Marigold oleoresin extracts is bioavailable, with dietary supplementation showing a five-fold increase in serum lutein levels (Chew 2003; Olmedilla 2002, 2003; Evans 2002; Slattery 2000; Hadden 1999). 34 See Cantrill (2004) for technical details of extraction and use.

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Garden Nasturtium (Tropaeolum majus). Nasturtium flowers and uncooked kale (a type of cabbage) contain particularly high levels of lutein. Other dietary resources of importance include ‘greens’ such as dandelion, nasturtium leaves, spinach, swiss chard and turnip greens. It is also found in zucchini, broccoli, brussells sprouts, garden peas, lettuce, tomatoes, oranges (including the juice) and celery – with lower levels being present in corn, carrots, eggs and kiwifruit. (Image courtesy J Busson CC-by-SA 3.0 Unported)

Stinking Roger: An Insecticidal Import

Stinking Roger (Tagetes minuta) has an equally diverse therapeutic reputation as the Tagetes species already discussed. The flowers were used in Argentinian folk medicine as an aperient, diuretic and diaphoretic remedy. It was popularly taken for gastrointestinal disorders (indigestion, gastritis), and as a mild laxative. The whole-plant decoction was recommended as a stomachic (to strengthen stomach function), as a general stimulant, as a sedative for hysteria and to promote menstrual flow. It was, however, also reputed to have purgative potential (Neher 1968). The Khaki Bush was imported into Australia by troops bringing it back after the African Boer Wars in the late 1800s. In Africa, where it was already naturalised, it was widely used for the treatment of infected wounds, chest infections (inhaled as an antiseptic agent, to dislodge mucous, and open the airways) and foot problems (bacterial or fungal infections, growths such as calluses and bunions). It

Stinking Roger (Tagetes minuta) is an introduced South American weed with antiparasitic and insecticidal properties. The crushed leaf has a particularly strong aroma, albeit not necessarily pleasant, hence the common name. Unfortunately, handling the herb can result in skin and eye irritation in sensitive individuals and wounds may turn septic. Moreover, it is not suitable for use as grazing fodder for cows as it imparts a highly disagreeable flavour to milk, cheese and butter products (Neher 1968).

has good antiseptic, antibacterial and antispasmodic properties. However, it should be avoided by those sensitive to the Asteraceae as its use has been linked to photosensitivity and skin reactions (dermatitis).35 The aromatic oil of Tagetes minuta has excellent insecticidal activity, particularly when combined with pyrethrum. An old recipe for killing maggots in wounds, which was said to be highly effective, combined carbon tetrachloride, wool fat, 5 per cent Tagetes oil, water and a preservative to make an emulsion. Even in 1926 the herb was regarded with 35 ɑ-terthienyl has been suggested as the phototoxic component of Tagetes oils. See SCCP (2005) for further details.


some interest, as Professor Rennie commented: There is yet another oil to which I should like to refer though it is derived from a plant not indigenous in Australia, namely, Tagetes glandulifera [T. minuta], which has become naturalised in Queensland and flourishes vigorously in the coastal districts of that State. In the flowering season it gives out a powerful and unpleasant odour, and it is chiefly from the flowers that the oil has been obtained. T. G. H. Jones, of the University of Queensland, has very carefully examined this oil and finds that in addition to terpenes, 30% ocimene, and 4% limonene, it contains two closely related olefinic ketones … having the same assemblage of carbon atoms as in citral and citronellal and which have not yet been found in essential oils. One of these ketones is remarkable (it has been called tagetone) in respect of its rapid absorption of oxygen and consequent resinification on exposure to air, a property which makes its isolation and investigation a matter of no small difficulty. It also possesses other remarkable characteristics.

The insecticidal properties of Stinking Roger have an extremely practical reputation. In Africa the plant was hung in doorways to repel flies, put in mattress stuffings as an insecticide, or planted in gardens to deter ants, bugs and mites. Various preparations (plant juice, or an oil from the leaves, flowers and seeds) were applied externally as a blowfly deterrent on animals, or the herb used to treat parasites in cattle.36 Studies have shown that the flowers had good mosquitorepellent activity, while the leaves were somewhat less active. Tagetes minuta was potently effective as a mosquito larvicidal agent, with T. patula exhibiting less activity. The effect was attributed to thiophene derivatives, compounds that are present in many of the Asteraceae. Other species with insecticidal and insect repellent activity include Tagetes filifolia, T. rupestris, T. subulata and T. erecta – with the latter showing activity against the mosquito Anopheles subpictus (Elango 2011; Lopez 2011; Seyoum 2002; Margl 2001; Broussalis 1999; Macedo 1997; Perich 1995, 1994; Sharma & Saxena 1994; Saxena 1992; Green 1991; Cribb & Cribb 1981). The essential oil of Aztec Marigold (Tagetes erecta) 36 Chamomile oil has also shown insecticidal activity against larvae of the blowfly (Lucilia sericata) responsible for myiasis (parasitic fly infestations). Lettuce (Lactuca sativa) oil was equally effective (Khater 2011). Chamomile oil also had good fly-repellent and moderate lice-killing (pediculicidal) properties against these pests of water buffalo in Egypt (Khater 2009). In addition, Chamomile flower extracts were strongly acaricidal against mites (Psoroptes cuniculi) (Macchioni 2004).

87 Tagetes minuta essential oil is sourced from the leaves stalks and flowers of the plant, just as the seeds are beginning to form. (Courtesy essentialoils.co.za)

was also larvicidal against the malaria and yellow fever mosquito vector Aedes aegypti – with investigations establishing that the roots and flowers had higher concentrations of the active thiophene components. The oil was piperitone rich (45.7%), with lesser levels of piperitenone (5.9%) and D-limonene (9.7%) (Marques 2011). Tagetes erecta root extracts have also shown good antibacterial and antifungal properties, as well as antiplasmodial activity against the malaria parasite Plasmodium falciparum (Gupta & Vasudeva 2010). Tagetes minuta and T. lucida (from Mediterranean sources) were found to have a good thiophene content, suitable for development as a biocidal crop with pest control attributes (Marotti 2010). Stinking Roger has even been grown in tobacco fields to discourage crop pests, notably root-knot nematodes. However, attempts to use the herb on a practical basis in California failed as its weedy habit overtook the crop. It was also virtually impossible to control its spread in irrigated groves. Tagetes erecta and T. patula, which have shown a similar resistance to nematode attack, have been used as a cover crop in Indian Tea plantations. They could demonstrably decrease the incidence of a pest known as the meadow eelworm (Pratylenchus pratensis). ɑ-terthienyl was identified as the nematicidal agent, which also had interesting photobiocidal properties with potential for use as a light-activated insecticide (Nivsarkar 1996; Neher 1968; Cribb & Cribb 1980; Webb 1948). Flower extracts of Tagetes patula have shown excellent nematicidal activity against the corn cyst nematode (Heterodera zeae), which was attributed to the phenolic components (flavonoids, phenolic acids) and ɑ-terthienyl (Faizi 2011b). Doubtless many other crops could benefit from the inclusion of these herbs in the fields.

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Aromatic Native Asteraceae

Pterocaulon sphacelatum. Niemenski, flickr)

An Australian species of the Asteraceae that also goes by the name of Stinking Roger (and Smelly Bush) is Streptoglossa odora (formerly Pterigeron odorus37) – a small herb of the inland spinifex regions in the northern tropics. Streptoglossa bubakii and S. decurrens have a comparable medicinal and aromatic reputation. Aboriginal people used the aromatic crushed leaves to make a decongestant decoction that was applied externally as a wash for the relief of influenza, head and chest colds, and headache. It has also been utilised as a plug of rolled leaves inserted in the nose, or the crushed herb (or infusion) inhaled. The herb, crushed on a stone and firewarmed, then placed on the chest, was regarded as being equally effective (Pearn 2005; Latz 1996; Wrightman 1994; Barr 1993; Smith 1993). These herbs contain essential oils with insect repellent properties. Extracts of Streptoglossa bubakii have fly-repellent activity and the oilrich leaf (essential oil level: 10–15% dry weight) contains caryophyllene and y-elemene (Pearn 2005; Southwell & Maconachie 1977). Other samples have given a lower essential oil yield (0.3%), albeit the main components were the same (Barr 1993). Smelly Bush leaf, as well as the caustic latex, has been used on scabies sores to relieve itching (Isaacs 1994; Lassak & McCarthy 1992). In the Northern Territory a few of species of Pterocaulon have a similar reputation for 37 In Australia the genus Pterigeron has been reclassified as Streptoglossa, which contains eight species. They are primarily found in northern Australia, although a couple of species range to New South Wales and/or South Australia.

(Courtesy

Craig

Stemodia viscosa (Scrophulariaceae). (Courtesy Dave Rentz, flickr)

the treatment of respiratory and skin problems – notably P. globuliflorus, P. serrulatum and P. sphacelatum (these Asteraceae herbs are discussed in greater detail in Chapter 3). Stemodia viscosa has been held in similar regard to Pterocaulon as a decongestant remedy. The fresh leaves were inserted into the nostril or the powdered dried leaf utilised a snuff. A lotion, prepared from the dried leaf decoction, was also considered useful for treating conjunctivitis or skin sores (Barr 1993).

 While the Asteraceae family contains many herbs of enduring therapeutic value, there are numerous other plants of medicinal importance that are native to these shores. The emphasis has been on tonic and wound-healing remedies, particularly for the treatment of bacterial disorders. Among the microbes responsible for bacterial infections, the Mycobacteria have been of special importance, primarily because


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these infections were so difficult to treat. This classification was responsible for the hideous scourge of leprosy and the chronic wasting associated with tuberculosis. Indeed, these conditions were highly unresponsive to most treatments until the advent of antibiotic drugs. However, a limited number of the herbal remedies that were used did have valid therapeutic effects – and have continued to be of interest for a number of different reasons, not least because of the advent of antibiotic-resistant bacteria and the prevalence of side-effects from antibiotic drugs.

In country areas most Australian households would have had a stock of remedies in the bathroom or kitchen cabinet that could be used for ‘just about anything’ – although ‘bush remedies’ were more convenient for travellers, particularly the bushmen and stockmen who worked around the countryside. Eucalypt Kino (left) was probably one of the most well known and widely available of the antiseptics, although the distillation of Eucalyptus oil in commercial quantities quickly saw it become an indispensible addition to the medicine cabinet.

Chapter 3

VALIDATING BUSH MEDICINES level of self-sufficiency. Sir James Robert Price and colleagues (1993) outlined the situation: ‘During the war [1939–45], serious thought had to be given to finding new sources for the essential drugs and other substances, such as vitamins, insecticides and insect repellents, which were significant for the health and competence of combatant troops. Although synthetic organic chemistry was making a rapidly growing contribution to the medical inventory, many essential drugs were still of plant origin (as many still are) and were largely imported from overseas.’ These circumstances inspired attempts toward a more comprehensive evaluation of the phytochemical properties of the native flora – a venture that was to become a herculean biochemical task. The initial investigations during the war had:

The development of Australian Eucalyptus oil as a household antiseptic and decongestant has certainly been the most outstanding and enduring achievement of therapeutic importance from this continent. However, the cultivation of the Eucalypt as an oil and timber resource was an enterprise that quickly dispersed across the globe. Indeed, China is now the major supplier of Eucalyptus oil on the international market. (Image courtesy Felton Grimwade & Bosisto’s Pty Ltd)

made evident the need for a systematic survey of pharmacological potential. So, in 1944, the CSIRO Division of Plant Industry planned such a survey to involve botanical, pharmacological and chemical collaboration. With one or two exceptions ... background pharmacological information was almost negligible. The starting point of the programme, therefore, was a preliminary botanical survey in the hands of Dr. L. J. Webb [published 1948 and 1952]. This soon revealed that the volume of chemical work would be far beyond the capacity of the chemists available, so the co-operation of the universities was sought, [particularly] those interested in natural product chemistry (Price 1961).

Despite the fact that native plants were utilised medicinally since the arrival of the First Fleet, in the long term most of the Australian flora gained little currency as medicinal or economic resources. Surprisingly enough, World War II was to have a major influence on the development prospects for Australia’s natural resources, fostering a dramatic change in attitude. The war effort unexpectedly highlighted the pitfalls of an exclusive reliance on overseas drug supplies. Serious shortages of medicines on the international market pressed home the point that Australia had neglected resources with phytochemical potential. These were sorely needed if this country was to achieve any

Over time, an extensive evaluation of the flora resulted. Although much was achieved, it has been an undertaking that continues to this day. It was a difficult, timeconsuming and, at times, seemingly impossible task to sort through the preliminary floral identification and chemical requirements of the project. 90

VALIDATING BUSH MEDICINES

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Native Antibacterials

Many plant-based remedies that provide successful folk medicines rely upon an effective antimicrobial action. Antibacterial activity has always been a vital component of remedies selected for general first aid and wound healing purposes. Therefore, it was logical that an evaluation of this aspect of the native flora attracted substantial attention and this became a serious post-war chemical challenge in the 1940s. When Howard Florey initially described penicillin ‘as a chemotherapeutic agent’ very little was known about the chemical potential of natural products. His discoveries were to inspire a colossal amount of interest across the world, which directly filtered through to the Australian scientific community. An early Australian report on Queensland plants tested against Staphylococcus aureus reviewed extracts prepared from 158 species belonging to 150 different flowering plant (angiosperm) families (Talcott & Webb 1948). Only four were found to have appreciable activity against Staphylococcus aureus – a common cause of food poisoning and infection. These were extracts of Canthium oleifolium (now Psydrax oleifolia; leaves), Crotalaria incana (leaves), Eugenia [Syzygium] smithii (leaf and mature fruits) and the naturalised Moluccella laevis (leaf and stem). The authors commented: ‘This is apparently the first record of Australian plants with antibacterial activity … belonging to the families Labiatae, Leguminosae, and Rubiaceae, and the genus Eugenia.’

Syzygium smithii (formerly Acmena smithii) is a native Lillypilly found in Queensland, New South Wales and Victoria. It may also occur in Tasmania. (Courtesy Melburnian)

Moluccella laevis is naturalised throughout much of the Australian continent – although it does not favour the tropics and is not found in the Northern Territory. (Courtesy Tsiaojianlee, Public Domain, Wikipedia)

Canthium oleifolium (now Psydrax oleifolia) is found in New South Wales and southern Queensland. (Courtesy Paul Campbell)

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bacilli, staphylococci and the acid-fast Mycobacterium phlei’ (Cleland 1950). Studies determined that the antibacterial activity of Geebung fruits could vary substantially. This was an important consideration that led to more detailed investigation. It was established that the very young or very old berries from Persoonia pinifolius had little effect against bacteria. The main activity was located only in the fleshy part (i.e. the juice extract) and peaked in mature fruits that were developing from green to purple. The results were significant: ‘[even] after drying and storage for several months berries still retained activity; which was stable and watery extracts remained active for at least 6 months’ (Atkinson 1949). Persoonia salicina and P. falcata berries were likewise found to be active. Unfortunately, the conclusion was that ‘Our Persoonia antibiotic may prove too toxic for chemotherapy except perhaps for local application where its ability to inhibit Pseudomonas pyocyanea and many common bacteria may be useful’.

The Woolly Rattlepod (Crotalaria incana) is a fairly widespread weedy species that is found throughout most of the Australian continent. (Courtesy Kim & Forest Starr, Hawaii)

Flowers of Crotalaria incana. (Courtesy Carlos Ivovic, flickr)

A massive review of the antimicrobial properties of the Australian flora was to follow. An important project initiated by Dr Nancy Atkinson and her team was to ultimately evaluate more than 1,200 plants. Dr J Burton Cleland reviewed these advances: ‘Many of the available native flowering plants were examined and it was found that an extract of the fruits [of one] of the Proteaceae, the Geebung, Persoonia juniperina, exerted an antibiotic effect on typhoid

Persoonia pinifolia. (Courtesy Dr David Midgley)


Persoonia pinifolia. (Courtesy Melburnian)

Milky Plum: Sacred Medicinal Plant The Milky Plum, Persoonia falcata, is a fairly widespread species throughout tropical Australia. In Queensland it ranges south to the central coast, extending into a drier inland climate. Milky Plum, which was widely employed as an antibacterial remedy in the Northern Territory and Queensland, was regarded as being a particularly good treatment for earache or infected eye problems (conjunctivitis). An infusion of the white inner bark scrapings, mixed with breast milk and water, could be easily utilised as ear and eye drops (Yirrkala Community School, 1990). Additionally, the bark has anti-diarrhoeal and expectorant properties. A leaf decoction, or the leaf simply chewed and the juice swallowed, was also highly regarded as a remedy for coughing, sore throat,

The Milky Plum (Persoonia falcata) is sacred to some Aboriginal tribes. It is considered to be a particularly powerful plant with an important role in magic ceremonies – including rites executed with harmful intent. It was reputed to inflict pain, and was even said to cause death if the magic was strong enough (Levitt 1981).

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oral thrush (candidiasis) or diarrhoea. In chest infections (including tuberculosis) it was used to loosen phlegm and promote its expectoration. The wound-healing properties of the leaves have even been utilised to heal circumcision incisions (Brock 1993; Barr 1988; Cribb & Cribb 1981).

Desert woomera. The tough wood of the Milky Plum was widely used to make spear-throwers (woomeras), boomerangs, axe-handles and music sticks. The bark contains approximately 9 per cent tannin. This could be soaked in water to make a preservative liquid for string or fishing lines, a process that increased durability. (Image courtesy Collection MB Abram Galleries, Los Angeles)

Persoonia falcata fruit. (Courtesy SGAP, Townsville)

Geebungs have been valued as a snack food wherever these trees were found. The genus contains 105 species, most of which produce small edible fruits favoured by Aboriginal people throughout the continent – although there is fierce competition from a wide range of wildlife, including kangaroos, rats, emus, smaller birds and the voracious feral pig. The small amount of flesh on the fruit has been described as tasting like sweet cotton-wool. Its popularity was mentioned in Tom Petrie’s Reminiscences of Early Queensland: ‘The fruit of the geebung [Persoonia], or “dulandella”, as the Brisbane tribe called it, was eaten raw, and greatly relished. The natives got dillies full of these in the right season. They swallowed the pulp and the stone, which they squeezed from the skin with their fingers. It is a small green fruit.’ Joseph Maiden recorded in his notes that: ‘These fruits are mucilaginous, insipid, and slightly astringent. They are largely consumed by aborigines, and also to some extent by small boys. Geebungs when dead ripe have a flavour which may be compared to that of apples, but the flesh is very stringy, and they have very big stones’ (Maiden 1888a).

The Geraldton Wax Plant (Chamelaucium uncinatum)

Geraldton Waxflower.

Chamelaucium is a small genus, endemic to Western Australia, that contains around a dozen species. The Geraldton Wax or Waxflower (Chamelaucium uncinatum) is the most familiar as it has been widely adopted in the ornamental


plant trade. The investigations of Dr Nancy Atkinson in the 1940s listed this species among the numerous plants whose medicinal potential was virtually unknown: ‘[the] Crude oil from the flowers of the Geraldton Wax plant (Chamelaucium uncinatum) was also found to possess antibiotic properties’ (Cleland 1950). The leaves have a pungent quality and were used by Aboriginal people to make a mouthwash. Analysis of the essential oil of the leaf has identified four chemotypes (Egerton-Warburton 1998): • Citronellal (55.36%): with lower levels of α-pinene (15.55%), geraniol (6.36%), limonene (4.93%), and α-terpinyl acetate (5.56%); • Limonene (49.91%): with α-pinene (27.04%), and low levels of citronellal (3%) and α-terpinyl acetate (3.23%); • α-pinene (54.07%): with limonene (12.85%), some citronellal (7.11%) and α-terpinyl acetate (4.83%); • Another oil form contains all three monoterpenes: citronellal (12.12%), limonene (23.98%) and α-pinene (22.95%), with lower amounts of linalool (4.73%) and α-terpinyl acetate (8.01%).

Bush Flower Essences are primarily utilised as emotional and spiritual healing remedies. There are many to choose from and the wildflowers of Western Australia have had a prized place in their development. Geraldton Wax Bush Flower Essence has been used as a remedy to balance the mind and emotional state. (Images courtesy Solara Antara, flowersforhealing.com)

There are a few other components of interest: • A ll four oil types contain small amounts of β-pinene (0.79–2.11%), globulol (1.98–3.12%), 1,8-cineole (1.17–2.14%), linalool (0.91–4.73%), geraniol (1.13–6.36%). • B orneol and α-terpinolene were present at low levels (3.13% and 2.03% respectively) in the citronellal-based oil.

There are a few species of Chamelaucium that have not yet been classified botanically – and the genus Verticordia, the ‘feather-flowers’, is very closely related – with V. brownii, V. plumosa and V. verticordina originally classified as Chamelaucium. The Pink Brownii or Pink Cauliflower (Verticordia brownii) has the particular distinction of being named after the famous botanist Robert Brown. It was one of the first of the genus collected by European botanists, being placed in Verticordia by the Swiss botanist Augustin Pyrame de Candolle, who established this genus in 1828.

Verticordia brownii. (Courtesy William Archer, esperancewildflowers.blogspot.com)

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Pterocaulon: A Fragrant Wound Remedy

A number of interesting candidates for antibacterial evaluation come from the Pterocaulon genus (Asteraceae family), many of which have distinct fragrant attributes. The Fruit-salad Plant or Applebush (Pterocaulon sphacelatum) and P. serrulatum (syn. P. glandulosum)1 have a good reputation in traditional Aboriginal medicine as decongestant and antiseptic remedies. The highly aromatic leaves were utilised as an inhalant or ‘rubbing medicine’ for treating colds, coughs, headache and fevers – particularly influenza. Although the herb was not usually taken internally, it has been popularly applied as a decongestant liniment on the chest, similar to Vicks VapoRub, for respiratory disorders (bronchitis, pleurisy). The sticky leaves can be simply crushed and inserted into the nostrils to clear the head or to relieve sinus congestion. Pterocaulon serrulatum, which is said to be among the more aromatic members of the genus, possesses insect-repellent properties – and has therefore been employed as a fumigant in campfires and as a mosquito repellent applied to the skin. The wash was also useful for healing sores or wounds, as well as eye inflammation (Latz 1996; Barr 1993). The healing attributes of Pterocaulon serrulatum were considered efficacious for spear injuries. FS Colliver (1972) commented: ‘the leaves of Pterocaulon glandulosus are used for stuffing up and rubbing over spear wounds in the arms and legs by the Koko-minni people and the charcoal from the wood of Grevillea striata is used to stop the haemorrhage in certain spear wounds’. Len Webb mentioned that the leaf

was potent only when green, and that an overdose could stimulate the heart (Webb 1948). The latter is interesting, as Vietnamese studies have shown that a flavonoid component, chrysosplenol C, has experimental cardioactive properties (Son 2011). Various species have been examined for antimicrobial properties and it appears that antifungal activity may be quite widespread in the genus. Argentinian investigations isolated flavonoids with antibacterial activity from Pterocaulon alopecuroides (Alarcon 2008). Brazilian studies of its potential as an antifungal agent determined activity against chromoblastomycosis, a chronic fungal skin infection (Daboit 2010). Other South American studies indicate that extracts of Pterocaulon alopecuroides, P. balansae and P. polystachyum have excellent antifungal potential. In particular, Pterocaulon polystachyum demonstrated activity against Cryptococcus neoformans

Pterocaulon serrulatum. (Courtesy Craig Nieminski) 1 There are a total of seven native Australian species. In addition to the above, they are P. globulus, P. nivens, P. redolens, P. spheranthoides and P. verbascifolium.

Pterocaulon polystachyum, from Flora Brasiliensis, Vol. 6/3, 1882.


(a fungal yeast that can cause meningitis) and various common dermatophytes (Microsporum gypseum, Trichophyton rubrum, T. mentagrophytes) responsible for skin infections (Stein 2006, 2005). In addition, this species has antioxidant, cytotoxic and experimental anticancer (anti-leukaemia) properties (Silveira 2009; Knoll 2006; Riveiro 2004; Mongelli 2000). Pterocaulon polystachyum, which has also been used for the treatment of digestive disorders, has been evaluated for antiparasitic properties. Plant extracts showed activity against the amoeba responsible for acute amoebic keratitis, Acanthamoeba castellanii. Extracts active against the parasite (66–70% lysis of trophozoites) were also able to prevent cyst formation, which is a significant obstacle to effective treatment of the condition (Rodio 2008). The leaf essential oil2 showed similar effects against Acanthamoeba polyphaga. However, it was not suitable for direct use – although the oil did have practical potential. Its incorporation into contact lens cleaning solutions was suggested for the prevention of amoebic contamination, which commonly results in keratitis – a very painful inflammatory condition of the cornea that can lead to impaired eyesight due to corneal scarring (Sauter 2011). While the herb requires further evaluation to establish its clinical usefulness, initial studies did not suggest that there were serious toxic concerns (Regner 2011). Pterocaulon sphacelatum is a native Australian medicinal herb with anti-mycobacterial potential (Meilak & Palombo 2008) that has also attracted interest as an antiviral agent. Extracts showed antiviral activity against poliovirus, with the isolation of a flavonoid (chrysosplenol C)3 that was active against picornaviruses (Semple 1999, 1998). A couple of related South American species have similar antiviral potential. Pterocaulon polystachyum demonstrated activity against Herpes simplex that appeared to be linked to coumarin components. Similar compounds were attributed with the antiviral (anti-HSV) activity of Pterocaulon alopecuroides extracts – which also possessed significant antioxidant and cytotoxic properties (Silveira 2009). 2 An uncommon compound, E-sesquilavandulyl acetate (43.8%), was identified as the major component in the oil, with smaller amounts of E-sesquilavandulyl (17.3%), β-caryophyllene (10%), ɑ-copaene (5.4%) and germacrene D (3.4%) (Sauter 2011). 3 Chrysosplenols B and C have also been isolated in other medicinal plants, e.g. Miliusa balanse (Son 2010; Huong 2005).

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Pterocaulon sphacelatum. (Upper image courtesy Craig Nieminski, flickr)

Interestingly the Brazilian plant Acanthospermum australe, which was also found active against Herpes virus, contained chrysosplenol D – as well as the flavonoid quercetin (Rocha Martins 2010). Chrysosplenols have attracted further interest because they have the potential to increase the efficacy of some antibiotics and antimalarial drugs (Kraus & Roy 2008). For instance, chrysosplenol D and chrysoplenetin from Artemisia annua demonstrated a very weak antibacterial (growth-inhibitory) action against drugresistant Staphylococcus aureus. This was significantly potentiated with the addition of berberine.4 These flavonols were also reported to potentiate the activity of artemisinin (an antimalarial drug sourced from Artemisia annua) against Plasmodium falciparum (Stermitz 2002). 4 Berberine is an exceptionally important alkaloid that is found in diverse plants – notably the genera Berberis, Hydrastis and Coptis, a number of which are valued herbs in Chinese medicine and Western herbal traditions. Berberine (and related isoquinoline alkaloids) have significant antimicrobial (antibacterial, antifungal), anticancer, neuroprotective, antidiabetic, antiinflammatory, antioxidant and cardiotonic properties.

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Chrysosplenol D is among the flavonoids isolated from the antimalarial herb Artemisia annua. (Courtesy Lloyd Crothers)

Chrysosplenol D, isolated from Vitex negundo var. cannabinifolia, exhibited activity against a number of food spoilage microorganisms (Escherichia coli, Bacillus subtilis, Micrococcus tetragenus, Pseudomonas fluorescens) (Ling 2010). Vitex trifoliata, which is one of the ten native Vitex species found in Australia, also contains this flavonoid. In the Northern Territory some Aboriginal tribes utilised an infusion of the pounded leaves as a wash for scabies and other itchy skin conditions (Barr 1993). Recent studies have taken an interest in the anticancer potential of chrysosplenol D and a related flavonoid, chrysoplenetin (Awale 2011) – which provides an interesting link to the Chinese folk medicine use of Vitex trifolia for the treatment of cancer (Li 2005).

Plectranthus: Aromatic ‘Native Mints’

Vitex trifoliata.

Vitex negundo. (Courtesy Dinesh Valke)

The genus Plectranthus is fairly large, containing over 300 species that range from Africa to India and Australasia – of which 42 are found in Australia. These herbs belong to the Lamiaceae, a family that contains many popular aromatic culinary herbs such as Basil (Ocimum spp.), Sage (Salvia spp.) and Mint (Mentha spp.). A number of aromatic herbs in this family have a great deal of similarity in their appearance – which has, at times, proved a significant obstacle to their classification. The genus Plectranthus is no exception.5 Various species have been identified as Coleus – although they have often been well placed in the closely related genera Anisochilus, Englerastrum, Solenostemon, Tetradenia and Isodon. Substantial debate regarding the classification of numerous species continues. Understandably, this has made their definitive botanical classification difficult, resulting in various discrepancies and diverse name changes in the literature. Biochemical studies may be of some value in solving these dilemmas. Recently, flavonoids in exudates from various species have been examined with the aim of clarifying the relationships within the Plectranthus genus (Grayer 2010).

5 The ‘Native Mints’ (genus Prostanthera) are also in Lamiaceae (see Volume 1).


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‘Variegated Mint’, Plectranthus madagascariensis. (Courtesy Kim & Forest Starr, Hawaii)

The genus Plectranthus has interesting antimicrobial potential. Even though little is known about the chemistry of the native Australian species, these plants have been employed in the traditional medicinal practices of tropical Africa, Asia and South America – mainly as healing agents for burns, injuries, sores, insect bites and allergic skin reactions. Indeed, more than 60 species have been recorded as possessing medicinal or economic value (Lukhoba 2006). This indicates that the native herbs could certainly be worthy of more intense scrutiny. Unfortunately, knowledge regarding their medicinal use in Australia is sparse – possibly because this was never recorded, and not because they remained unused. Walter Roth (1903) noted that an infusion of a tropical Queensland Plectranthus congestus (leaf and branchlets) was employed for ‘internal complaints’. This is a rather unusual recommendation as few herbs were taken internally by Aboriginal people. The leaves of this species have been applied as an antiseptic dressing for wounds in Papua New Guinea, which suggests antibacterial potential. It was also said to be useful for treating the parasitic skin condition scabies (Woodley 1991; Holdsworth 1977). Certainly a number of native species have shown strong acaricidal activity against the horticultural pest, red spider mite (Tetranychus urticae; see Table 3.1), which suggests these plants could have more extensive insecticidal potential.6

6 Coleon A from Plectranthus saccatus has shown strong antifeedant activity against the African/Egyptian cotton leafworm (Spodoptera littoralis), a significant crop pest (Wellsow 2006).

The common garden Coleus (Plectranthus scutellarioides, syn. Solenostemon scutellarioides) has innumerable colour variations. This herb was among the species collected in Australia by Robert Brown in 1810 and placed under Ocimum scutellarioides. The herb is found throughout northern Australia (Queensland, Northern Territory and Western Australia), ranging along the Queensland coast to Brisbane. (Images courtesy Kim & Forest Starr, Hawaii)

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The Plectranthus genus is rich in essential oils, thus it is unsurprising that a number of native Australian species have distinctive fragrant characteristics. They include P. argentatus, P. parviflorus and P. graveolens. The latter was collected by Joseph Banks and Daniel Solander at the Endeavour River in northern Queensland – in addition to P. apreptus, P. foetidus and the related species Teucrium argutum. Samples of Plectranthus parviflorus were collected from Botany Bay. (Upper image courtesy Kim & Forest Starr, Hawaii; lower image courtesy Melburnian)

A couple of Plectranthus species have gained prominence as Asian medicinal herbs – P. amboinicus and P. barbatus. Their traditional uses provide some interesting insights into the pharmacological potential of the genus. Plectranthus amboinicus has been recommended for respiratory problems, feverish conditions, and infections (including meningitis).

Plectranthus barbatus was similarly taken for respiratory tract disorders and diverse infections (Lukhoba 2006). These species have demonstrated antibacterial and anti-inflammatory properties that would certainly support their traditional use. Studies of Plectranthus amboinicus indicate an interesting range of activity: antifungal, antiprotozoal (antimalarial, anti-giardia), diuretic, anti-mycobacterial, bronchodilatory and anti-tumour – as well as antiviral activity against HIV and Herpes simplex-1 (HSV-1). Plectranthus barbatus also has anti-HIV properties, as well as valuable hypotensive and spasmolytic attributes (Patel 2010; Lukhoba 2006; Matu & van Staden 2003).

The aromatic qualities of Plectranthus amboinicus have resulted in a variety of common names such as Mexican Mint, Spanish or Mexican Thyme, Cuban Oregano and Indian Borage. Interestingly, there are old Thai drug recipes that included Plectranthus amboinicus in treatments for venomous bites – and it has shown activity as an antidote against scorpion venom (Uawonggul 2006). In Queensland, this species is found as an introduced ornamental around the south coast (Gold and Sunshine Coasts) – and is also found around Sydney in NSW. (Image courtesy Kim & Forest Starr, Hawaii)


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Table 3.1 Summary of Traditional Uses of Medicinal Plectranthus Species Plectranthus amboinicus (syn. Coleus amboinicus) Synonyms: Coleus aromaticus Plectranthus aromaticus

Traditional uses (source references Waldia 2011; Lukhoba 2006) and investigations (as per reference cited) India and Africa: utilised as a remedy for diverse digestive disorders (indigestion, dyspepsia, diarrhoea), and employed as a carminative (relieve flatulence). Chinese medicine: cough, fevers, sore throat, mumps, mosquito bites (Chiu 2012). Heart: recommended for the treatment of congestive cardiac failure. Feverish conditions and infectious disorders (including cholera and meningitis). Neurological problems (including epilepsy, convulsions); extracts have shown antiepileptic activity (Buznego 1999). Respiratory problems: chronic coughing, whooping cough, asthma, bronchitis, pharyngitis, catarrhal congestion. Genitourinary tract disorders: kidney troubles, vaginal discharge, used after childbirth. Skin disorders: applied to burns, poultice for centipede and scorpion bites in Malaysia; skin ulceration associated with leishmaniasis in Brazil (Franca 1996) Note: There is a report of leg ulceration due to the use of this herb. This was attributed to allergic contact dermatitis, suggesting some individuals may be sensitive to the plant (Chang 2005). Antiparasitic: studies have confirmed the activity against Leishmania, although Plectranthus grandis extracts were significantly more active against L. amazonensis (Tempone 2008). Essential oil: mosquito larvicidal activity against malaria vector Anopheles stephensi (Senthilkumar & Venkatesalu 2010). In vivo studies of antimalarial (antiplasmodial) activity of leaf extracts showed reduced levels of parasitaemia in mice (Periyanayagam 2008). Note: Essential oil constituents: carvacrol (28.65%), thymol (21.66%), α-humulene (9.67%), undecanal (8.29%), γ-terpinene (7.76%), ρ-cymene (6.46%), caryophyllene oxide (5.85%), α-terpineol (3.28%) and β-selinene (2.01%) (Senthilkumar & Venkatesalu 2010).

Plectranthus barbatus (syn. Coleus forskohlii) Synonyms: Coleus kilimandschari Coleus coerulescens Coleus barbatus Plectranthus forskohlii Plectranthus kilimandschari Plectranthus grandis

ENT: acute oedematous otitis (ear infection); extracts have shown good activity against Staphylococcus aureus (Nogueira 2008). Eye disorders: conjunctivitis. Anti-inflammatory, anti-arthritic: used for inflammatory disorders and swelling in Taiwan; anti-arthritic activity demonstrated with potential for use in combination drug therapy (Chang 2010, 2007). Anti-inflammatory and analgesic properties shown for aqueous herb extracts; high levels of the anti-inflammatory agent carvacrol (1.88 mg/g extract) were isolated (Chiu 2012; Ravikumar 2009). Extracts have shown anti-inflammatory and protective effects against bone destruction (Hsu 2011). Antitumour and anti-inflammatory activity for leaf extracts. Used as an anticancer remedy in Brazil (Gurgel 2009). A diterpene (coleon U) isolated from Plectranthus grandidentatus has shown antiproliferative effects on several human cancer cell lines (Coutinho 2009). Coleon U also has substantial antibacterial properties and moderate antifungal activity. Coleon A has antibacterial properties to a lesser extent (Wellsow 2006). Antidiabetic and cholesterol-lowering properties: hypoglycaemic and antihyperlipidaemic effects involving restoration of pancreatic tissue function and insulinotropic effect (Koti 2011; Viswanathaswamy 2011). Kidney protective: traditional use for treating renal calculi (Koti 2011); ethanol extract showed nephroprotective and antioxidant activity, plus strong diuretic effect in animal studies (Palani 2010). Respiratory tract disorders (infections of the throat and mouth, tonsillitis, pneumonia). Diverse other infections: genitourinary tract disorders including syphilis; ear and eye infections. Gastrointestinal tract: nausea, stomach-ache, constipation, gastric discomfort. Studies of P. grandis have shown gastroprotective properties due to diterpene components (Rodrigues 2010); also anti-ulcer and antisecretory properties (Schultz 2007). Hepatoprotective in rats with obstructive cholestasis (Battochio 2005). Painful conditions: gastritis, intestinal spasms, abdominal pain, dysuria, muscular pain, backache, bone dislocation, neck stiffness. Investigations have shown intestinal relaxant and antispasmodic activity for the essential oil which was linked to α-pinene (Camara 2003).

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary Nervous system: convulsions, insomnia, psychiatric problems (including ‘madness’, depression), mental retardation. Herbal tea has acetylcholinesterase inhibitory properties; rosmarinic acid crosses the blood–brain barrier (Fale 2012, 2011). Leaf extracts have anticonvulsant properties (Borges Fernandes 2012). Fertility: use as an emmenagogue, oral abortifacient or contraceptive. Animal studies show an anti-implantation effect. Skin: skin rashes, fungal infections (ringworm, candida). ENT: earache Eye: conjunctivitis; herb used as source of anti-glaucoma drugs. Anti-parasitic: traditional use for treating fevers and malaria; antiplasmodial activity against Plasmodium falciparum, possibly due to abietane diterpene components (AlMusayeib 2012; Van Zyl 2008). Diuretic activity for leaf extracts (Patel 2010).

Plectranthus vettiveroides (syn. Coleus vettiveroides) Note: This species and P. rotundifolius may be the same, although this requires clarification

Similar reputation to the above for gastrointestinal and neurological disorders (including ‘insanity’). Genitourinary problems: notably strangury; genitourinary ‘stimulant’ effect; utilised as emmenagogue for menstrual disorders. Eye problems (burning eyes). Skin problems (skin infections, leucoderma) and leprosy. Fevers and ‘intrinsic’ haemorrhage. Other: useful thirst-quenching properties and has been used to promote hair growth.

Forskolin

Plectranthus barbatus. (Courtesy Tarcisio Kennedy)

Forskolin (a labdane diterpene that was originally named coleonol in 1974) was a particularly important chemical discovery from Plectranthus barbatus (syn. Coleus forskohlii). Applied to the eye it is an effective antiglaucoma drug that lowers intra-ocular pressure. Forskolin has been extensively investigated as a hypotensive and cardiotonic agent – which certainly reflects the traditional use of this herb for heart and circulatory problems (angina, muscular pain, hypertension, haemorrhage). Forskolin has been utilised clinically as a vasodilatory, hypotensive, cardiotonic agent. While it appears to have therapeutic potential for stroke (cerebral

vascular insufficiency), monitoring is required with some drug combinations (particularly blood-thinning medication) because it has shown inhibitory effects on platelet aggregation. Forskolin has practical potential for numerous other conditions due to muscle-relaxant and antispasmodic properties. Clinical studies suggest its use for the treatment of asthma and other forms of respiratory distress. Furthermore, it may be beneficial for digestive disorders such as malabsorption syndromes due to a stimulatory effect on digestive secretions – although care should be exercised in individuals with gastric ulceration (Altern Med Rev 2006). Interestingly, Plectranthus barbatus has been employed as an anti-ulcer remedy in Brazilian folk medicine – and an antisecretory diterpenoid (plectrinone A) was isolated from herbal extracts (Schultz 2007). Recently, interest has been expressed in the potential of forskolin as a weight-loss agent for treating obesity. Some clinical results have also suggested benefits for bone mass and testosterone levels, albeit unconfirmed. This has, unfortunately, led to opportunistic marketing enterprises touting its use as a body-building supplement (Godard 2005). Obviously forskolin has a pretty impressive therapeutic repertoire. Even so, it appears that there is room for more clinical advances, with


forskolin showing experimental anticancer activity, antidepressant, and immunostimulating properties. It has potential for use in thyroid problems (increases thyroid hormone production and release), allergic disorders and psoriasis (Altern Med Rev 2006). Some research has focused on the local application of forskolin to induce a suntan and its ability to prevent the skin burning on UV light exposure. It does this by the induction of eumelanin production in the skin and, despite worries about an adverse stimulatory action on melanin cells, animal studies have not shown untoward side-effects. Indeed, recent investigations suggest that forskolin may have a DNA protective effect (Passeron 2009; Spry 2009; Minkel 2006). Moreover, forskolin has shown an ability to enhance the activity of antibiotics used against urinary tract infections7 – although this requires confirmation (Khamsi 2007). Investigations of the ability of forskolin to affect acetylcholinesterase levels have also focused on chemoprotective potential against organophosphate poisoning, including that associated with chemical warfare agents (Curtin 2006).

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have similar antibacterial properties, with the latter also showing anti-yeast activity (Goncalves 2012; Mohamed 2006). Plectranthus barbatus (root and leaf ) and P. neochilus (leaf ) showed strong anti-Candida activity that support the traditional African use of these plants for infective skin disorders (Runyoro 2006; Tempone 2008; Kisangau 2007). The latter is also utilised in the treatment of respiratory infections in South Africa, which suggests the herb has additional antimicrobial value (York 2011). Certainly, this tends to indicate that further evaluation of the Australian genus is warranted.

7 Plectranthus ornatus and P. fruticosus also contain diterpenes, some of which have antimicrobial properties. The latter has been used as a burn-healing remedy in Poland (Lukhoba 2006).

Antifungal Plectranthus

The essential oils of various species of Plectranthus have shown good antimicrobial potential, with some plant extracts demonstrating strong antifungal activity. Studies of Plectranthus cylindraceus, a herb used as a topical disinfectant in Oman, confirmed a broadspectrum antimicrobial activity for the essential oil. It was active against bacteria (Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis), yeast (Candida albicans) and a wide range of fungi (Alternaria alternata, Bipolaris sp., Curvularia lunata, Fusarium oxysporum and Stemphylium solani) – including dermatophytes responsible for skin infections (Microsporum canis, M. gypseum, Trichophyton rubrum) (Marwah 2007). Plectranthus amboinicus and P. coleoides essential oils

The Blue Coleus or Lobster Flower (Plectranthus neochilus) is a South African native that can be found around the Sydney region. Like many others in the genus it has fragrant qualities, albeit described as being ‘unpleasantly aromatic’. This is a pollution-tolerant herb with fluorineretentive qualities that is said to be able to help improve air quality (Campos 2010). This species has been utilised in the treatment of hepatic insufficiency and dyspepsia in Brazil, the fresh leaves made into an infusion (Duarte & Lopes 2007). The essential oil has also shown antiparasitic (anti-schistosomal) properties worthy of further investigation (Caixeta 2011). An ointment made from Blue Coleus, which was utilised for promoting healing following sterilisation in cats, also gave good results as a local analgesic application (Ferreira nd).

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Other species with similar interesting antimicrobial properties include Plectranthus elegans, P. incanus, P. grandidentatus and P. heretoensis. The latter two contain diterpenoids active against drug-resistant bacteria (MRSA and VRE) (Marwah 2007; Gaspar-Marques 2006). Plectranthus amboinicus essential oil has broadspectrum fungitoxic properties with potential for use as an antimicrobial to prevent food spoilage (Murthy 2009). In addition, rosmarinic acid was identified as a major component of Plectranthus barbatus and P. ecklonii extracts with antibacterial properties against cariogenic bacteria (Streptococcus sobrinus, S. mutans), making these herbs useful candidates for oral care purposes (Figueiredo 2010). Plectranthus ecklonii possessed additional activity against mycobacteria (M. tuberculosis) and Listeria (L. monocytogenes, a gram-positive bacterium). In particular, parviflorons D and F from herb extracts demonstrated broad-spectrum antibacterial properties that suggest good antiseptic potential. The herb has been used as a remedy for skin infections in Africa (Zimbabwe) – as well as having a reputation for being useful in gastrointestinal distress (stomachache, nausea, vomiting) and meningitis. Extracts contain flavonoids, as well as caffeic acid derivatives (nepetoidins A and B)8 – the latter being of interest due to their antifungal activity, as well as possessing potent free-radical scavenging properties superior to rosmarinic acid and gallic acid (Nyila 2009; Lukhoba 2006; Grayer 2003; Nyanyiwa & Gundidza 1999).

Plectranthus ecklonii, which is naturalised in New South Wales and Victoria, is a medicinal species with antifungal, antibacterial and anti-inflammatory potential. (Courtesy kaiyanwong223, flickr) 8 These compounds have been found in leaf extracts of a number of Plectranthus species (see Lukhoba 2006).

Analysis has shown that the essential oils of the different species can differ markedly in their chemical components: • P lectranthus barbatus (fresh aerial parts): β-farnesene (24–86%), D-germacrene (21.4%), α-copaene (12.68%), α-zingiberene (4.44%) (Marques 2012). • P lectranthus barbatus (dried aerial parts): caryophyllene oxide (36.41%), α-copaene (17.12%), α-pinene (10.92%), β-farnesene (6.9%), α-zingiberene (1.17%) (Marques 2012).9 • P lectranthus barbatus (essential oil): substantial differences occurred in the main component of the oil sourced from different parts of the plant: α-pinene (leaves: 22.2%); β-phellandrene (stems: 26.1%); (Z)-βocimene (roots 37.6%) (Waldia 2011). • P lectranthus coleoides: thymol (57.57%), y-terpinene (15.37%), p-cymene (9.07%), trans-caryophyllene (5.81%) (Mohamed 2006). • P lectranthus cylindraceus: carvacrol (46.8%), α-terpinolene (18.2%) (Marwah 2007) • P lectranthus fruticosus: sabinyl acetate at very high levels (60%) (Fournier 1986). • P lectranthus grandis9: trans-caryophyllene (31.3– 40.2%), germacrene D (12.5–24.5%), eugenol (15.4%) (de Albuquerque 2006). • P lectranthus melissoides (oil): carvacrol (41.3%), p-cymene (17.4%), y-terpinene (10.1%) with smaller amounts of methyl thymol (3%), thymol (7.9%) and carvacrol acetate (4.6%) (Waldia 2011). lectranthus neochilus: β-caryophyllene (28.23%), • P α-thujene (12.22%), α-pinene (12.63%), β-pinene (6.19%), germacrene D (5.36%), and caryophyllene oxide (5.37%) (Caixeta 2011). • P lectranthus ornatus: trans-caryophyllene (9.6– 62.4%), eugenol (38.0%), thymol (14.1%) (de Albuquerque 2006). Other samples from the dried aerial parts differed somewhat: caryophyllene oxide (10.73%), β-farnesene (18.5%), α-pinene (10.83%), α-thujene (17.6%), β-bourbonene (7.98%). However, volatile oil samples from fresh aerial parts differed considerably: β-farnesene (28.83%), 1-octen-3-ol (11.85%), β-bourbonene (8.07%) (Marques 2012).

9 Marques (2012) showed that the fresh volatile oil from samples of P. barbatus and P. grandis were very similar. P. grandis (fresh aerial parts) contained β-farnesene (16.22%), D-germacrene (21.4%), α-copaene (12.38%). Dried samples differed: caryophyllene oxide (35.03%), α-copaene (17.85%), α-pinene (8.56%), β-farnesene (4.31%). β-caryophyllene, which begins to oxidise immediately upon air exposure, has shown only a weak sensitising capacity. However caryophyllene oxide, which was found at higher levels in dried material, has been identified as an allergen of moderate strength (Marques 2012).


Sneezeweeds C entipeda: A Widespread Australian Genus

Plectranthus coleoides has been utilised medicinally in India – the leaf juice was taken by pregnant women to moderate the pain of delivery. The leaf paste was applied to wounds to promote healing, or the leaf juice boiled with coconut oil and used as a lotion to stimulate hair growth (Ignacimuthu 2006). (Image courtesy Jerzy Opiola, Wikimedia Commons)

Toxicological reservations have been expressed regarding the oil of Plectranthus fruticosus (pictured above). Abortifacient properties and foetal toxicity were shown in animal studies and sabinyl acetate was identified as the abortifacient agent – although it was not foetotoxic. This compound is also present in Spanish Sage oil (Salvia lavandulifolia), although there can be large variations (0.1–24%) dependent upon the subspecies (highest levels were found in subsp. velera), chemotype and plant origin. It is also a component of Savin oil (Juniperus sabina) which has abortifacient properties (Fournier 1992, 1992, 1986; Chamorro 1991). Low levels may be present in Celery seed oil, Bergamot oil and Oregano oil (Oreganum vulgare subsp. vulgare) (www. thegoodscentscompany.com). (Image courtesy Kim & Forest Starr, Hawaii)

Old Man Weed (Centipeda cunninghamii). (Courtesy Michael O’Dwyer, Friends of the Earth, Melbourne)

The aromatic herb, Spreading Sneezeweed (Centipeda minima, formerly C. orbicularis or Myriogyne minuta), earned its common name due to a potent sternutatory effect. It provided an excellent snuff that was exceptionally effective at inducing sneezing – a property deemed useful for relieving congestion of the head during colds or influenza. This small plant is widespread throughout the Indo-Pacific region and has been used in a remarkably similar manner wherever it grows – in countries ranging from China and Japan, to India, Malaysia, the Philippines and Australia. Indeed, the herb’s natural range extends as far as Madagascar. In Australia two other closely related species were used interchangeably as ‘Sneezeweeds’ – the Common Sneezeweed (Centipeda cunninghamii), and the Desert Sneezeweed (C. thespidioides). Overall there are eight native species, all of which are widely distributed across the continent: • Centipeda cunninghamii, which is the most widespread, is found throughout the continent, extending to Tasmania; • Centipeda borealis and C. minima subsp. macrocephala: Western Australia, Northern Territory, Queensland; • Centipeda minima subsp minima has a wider distribution from the northern tropics to South Australia, New South Wales and Victoria;

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• Centipeda crateriformis, C. nidiformis, C. pleiocephala and C. thespidioides share a similar distribution (WA, NT, Qld, NSW, Vic., SA); • Centipeda racemosa (WA, NT, Qld, NSW), however, does not extend to the southern states. Australian Aboriginal people crushed Sneezeweed and inhaled the vapour to ease head congestion or headache. Alternatively, it could be bound around the head to inhale the aroma, although the latter practice had one substantial pitfall. All these herbs are extremely aromatic with a fragrance that is usually regard as being quite ‘objectionable’.10 More unusual was its deployment as a substitute for the narcotic plant Pituri (Duboisia hopwoodii) or the native ‘Wild Tobacco’ (Nicotiana spp.) when these were unavailable (Latz 1996). Joseph Maiden (1888b) mentioned that in Indian herbal traditions the remedy was not only valued for its decongestant abilities, adding: ‘The natives of India consider it a hot and dry medicine, useful in paralysis, pains in the joints and special diseases; it is also used as vermifuge [Cyclopedia of India]’. The seed and herb have been employed for the treatment of toothache, hemicrania (headache), and worm infestations (Satyavati 1976). In the late 1800s Sneezeweed was a popular remedy for treating the eye infection known as ‘sandy blight’. Joseph Maiden (1888a) noted: ‘if this plant only partially realised the expectations formed of it, it will be a valuable addition to our indigenous vegetable materia medica’. The words of Thomas Mitchell, on his expedition from Sydney to the Gulf of Carpentaria, provide an insight into the seriousness of this condition: ‘This morning I awoke completely blind, from ophthalmia, and was obliged to have poultices laid on my eyes; several of the men were also affected in the same manner. The exciting cause of this malady in an organ presenting a moist surface [the eye] was, obviously, the warm air totally devoid of moisture, and likely to produce the same effect until the weather changed’ (24 January 1846). However, his treatment the next day was somewhat more invasive, and decidedly less pleasant, than the herbal alternative: ‘Dr Stephenson having recommended the 10 Sneezeweeds have been utilised as ant-deterrents around campsites. The herb has also been a suspected stock poison (Latz 1996).

application of leeches, and having observed them in the ponds at Nyingan, I sent William Baldock and Yuranigh there in search of some, and they brought back enough. Fourteen were applied to my eyes the same afternoon.’ Fortunately, his eyesight improved quite rapidly over the following days. The whole experience was extremely difficult for the surveyorexplorer as the awful thought of failure loomed: ‘to have abandoned the undertaking at that point, would have been almost as painful to me as the other alternative’ (Mitchell 1848).

The Medicinal Leech

Invoice for ‘57 Choice Leeches’ sold to Swindon businessman Mr John Green, 12 May 1870. This unusual Victorian illustrated invoice was from Fitch & Nottingham, 16 & 17 St Peter Street, Hackney Road, London. (Image courtesy Swindon Collection, Central Library, Berkshire)

There are more than a hundred different native species of leech in Australia. Surprisingly, they are actually a type of segmented worm (Annelids) and therefore closely related to earthworms. Leeches contain an anticoagulant that they use to facilitate blood flow from their host – and this has extremely useful medicinal properties. Indeed, leeches continue to be utilised today for some forms of surgery, notably microsurgical procedures involving tissue damage that requires the removal of clotted blood. An interesting Belgian study on leech feeding behaviour examined some old methods of motivating uncooperative leeches – which can, at times, be unenthusiastic about the job.


Despite rumours to the contrary, the use of sour cream did not appear to change matters much, and garlic was simply lethal – a fatally attractive arrangement. However, nineteenth-century physicians also dipped leeches in beer before use. Unfortunately, this strategy did not appear to help matters much either: ‘After exposure to beer leeches changed behaviour, swaying their forebodies, losing grip, or falling on their backs’. It appears that the leeches became quite inebriated when they sampled Guinness Stout and Hansa Bock (Baerheim & Sandvik 1994).

Leeches for sale in the Egyptian Bazaar, Istanbul. (Courtesy Marcus Beard, flickr)

It was no wonder that interest was quickly aroused in any remedy with such singular efficacy. Maiden’s writings help to trace some of Sneezeweed’s medicinal history: I find from a communication of Baron Mueller, that for some time past he has had an idea that Myriogyne [Centipeda] might be utilised for medicinal purposes, and that he had actually submitted it to Dr. Springthorp, an eminent physician in Melbourne, for the purpose of experiment. The Baron, however was not aware of its efficacy in simple ophthalmic inflammation, and he regarded the discovery as interesting. I mention this as a matter of justice to Dr. Jockel who, I believe, is the first medical man in Australia who has proved the value of Myriogyne in the case of ophthalmia. This weed, growing as it does on the banks of rivers and creeks, and in moist places, is common to all the Australian colonies and Tasmania, and it may be regarded as almost co-extensive with the disease it is designed to relieve. It is described in the Flora Australiensis … and figured amongst Baron Mueller’s plants of Victoria. In the document relating to

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the Intercolonial Exhibition, 1866–1867, it is noticed as remarkable for its sternutatory properties, and recommended for the manufacture of snuff (Maiden 1898).

The willingness of some enterprising medical practitioners of the time to investigate native plant remedies was heartening. They quickly embraced the practical usefulness of many herbs – without the derision that later haunted the use of medicinal plants following the development of synthetic drugs. The Reverend Dr Woolls gave an interesting account of the rather serendipitous investigation of Sneezeweed. In a letter to the editor of the Sydney Morning Herald, Christmas Day 1886, he reported: Some weeks since, the Rev S. G. Fielding of Wellington, called my attention to a weed (known to botanists as Myriogne minuta, of the Compositae order) which he stated had been used with success in cases of blight. Being anxious to test the efficacy of the remedy, and to ascertain whether any bad effects would arise from its application, I placed some of it in the hands of Dr. Jockel of this town who has furnished me with the following remarks: ‘I have much pleasure in testifying to the efficacy, in cases of ophthalmia, of the plant which you so kindly sent me. A case came under my notice a few days ago of a drover who was suffering from a severe form of purulent ophthalmia, contracted up country. I made an infusion of the plant according to directions, and the first local application seemed to have almost a magical effect. The man expressed himself relieved at once of the intense smarting which he had previously suffered. He got on so well that in 2 days he was able to start back up country again, and could hardly express his gratitude for the very great relief afforded. Louis C. Jockel’ (Maiden 1888b).

The remedy rapidly entered into popular use. Maiden later commented: ‘this use of the plant as a cure for sandy blight is fairly well known in the Colony; how long it has been known I cannot say. It was packed in tins by one enterprising firm and sold as “Magic Ophthalmia cure” with what business results I do not know. It can be said of this remedy that if its effects are not beneficial in any particular case, they can scarcely be injurious’ (Maiden 1898). Although the herb had obvious successes in many cases of ‘ophthalmia’, there would have been some limitations on its efficacy. Because eye inflammation can be due to a variety of pathogens, doubtless some of them would have been resistant to the remedy. Additionally, the quality of the preparation would have had an

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important influence – and some caution was in order regarding its application. The Revered Woolls (1887) warned: ‘Myriogyne minuta in decoction has been found useful in cases of ophthalmia or blight, but careful observation is required to ascertain the proper proportion in which it should be used, and also the best method of application. If the decoction is too strong it occasions much pain and therefore care is necessary in the preparation of it.’ Over the last century Sneezeweed, which was known colloquially as the ‘Old Man Weed’, has continued to be used by Aboriginal people. In 1974 an article by Alistair Campbell on the ‘pharmacy’ of the Victorian Aborigines deemed Centipeda cunninghamii worthy of further examination: ‘It was used in medicine by Aborigines of Lake Hindemarsh in 1873. It was still in use in 1970 at Cummeragunga where a decoction was made by boiling the plant in water and straining. A sample of the decoction was obtained, it was black in colour. It was taken as a cure for ill-health including tuberculosis and as a lotion for skin infections. Its active principle, if any, is unknown and does not appear to have been investigated.’ The extended use of the herb (for around two years) was even said to help resolve a case of tuberculosis. The lotion has also been valued for treating diverse skin disorders such as rashes, ulceration and acne. CSIRO (Commonwealth Scientific and Industrial Research Organisation) investigations in Australia determined that the herb had a slight anti-pyretic and anti-diuretic activity (Collins 1990).

Cosmetics from Centipeda Overall, more than 60 components have been identified in Centipeda cunninghamii essential oil, extracted from the leaves and flowering tops of the shrub – albeit most were present only in very small amounts. The oil was found to be primarily composed of cis-chrysanthenyl acetate (sample 1: 30.57%; sample 2: 13.54%) or cischrysanthenol (sample 2: 23.89%; sample 1: 9.7%) and myrtenyl acetate (22.97–23.94%). Smaller amounts of thymol (4.64–6.08%), myrtenol (5.85–8.2%) and myrtenal (0.17– 2.78%) were also present (www.phyoxolin.com. au; see Beattie 2009 for a full chemical review).

A diverse range of compounds can also be found in plant extracts. They include flavonoids from the flowers, caffeic acids from the stems (e.g. chlorogenic acid), a thymol derivative and a sesquiterpene lactone (arnicolide). Extracts possess potent anti-inflammatory and antioxidant properties, with some components exhibiting activity comparable to the green tea antioxidant epicatechin (Beattie 2009; Gabriel 2005). Extracts have also shown antibacterial and antifungal properties (Palombo & Semple 2001; Hill 1997). Centipeda has thus been suggested to have particular application as a skin-healing, rehydrating and cellular protective agent. The patented herbal products Phyoxolin and Plantolin have been marketed as anti-ageing, anti-wrinkle, soothing, restorative products useful for irritated and cracked skin disorders (dermatitis), herpes infections, psoriasis, eczema, acne, rosacea, sunburn and general purpose skin cosmetic use (Beattie 2009; Gupta & Hoyt 2006; www.phyoxolin.com.au; www.plantolin. com). Other suggests include the use of the herb for oral disorders such as periodontal infections and gingivitis (D’Amelio & Mirhom 2005). Centipeda cunninghamii-based products have also been proposed for use for baby skin disorders such as nappy rash – as well as shaving creams, toothpaste formulations, hair care, bath products and shower gels. It appears to be suitable for a wide range of other cosmetics, skin lotions and creams – including antibacterial face washes, makeup removers and hydrating face masks (European Patent EP0988044).

Centipeda in Chinese Medicine The varied use of Centipeda minima in Chinese medicine traditions is illustrative of the extensive therapeutic potential of this herb. The plant was collected and dried when in full flower, or when the flowers were beginning to open, and simply utilised as an infusion. Similar to the use of Sneezeweed in Australia, it was regarded as having antitussive, expectorant, anti-allergic, anti-asthmatic, diaphoretic and anodyne (pain-killing) properties – being primarily recommended as a respiratory tonic and


to improve eyesight. Not only was it useful for treating the common cold and rhinitis, it was taken to ease coughing (including whooping cough), relieve rheumatic pain, alleviate dysentery and treat snakebite. The herb has a broad spectrum of antibacterial activity High grade granulated (against Pseudomonas Centipeda herb for use in sp., Proteus sp., Bacillus herbal dispensary. (Image courtesy Acuneeds Pty Ltd, typhi, B. dysenteriae and Staphylococcus aureus) Sydney) (Yeung 1985). It was also utilised for treating ‘internal injuries’ – although a more unusual recommendation was the use of the herbal decoction (taken alone or with wine) to counteract opium poisoning (Perry & Metzger 1980). In Nepal, the popular use of Sneezeweed juice (inhaled or taken internally) for coughs and colds inspired investigations of its antiviral potential. Extracts demonstrated activity against the Sindbis, Herpes simplex and polio viruses. Antibacterial activity was confirmed against Bacillus subtilis and Staphylococcus aureus, with this activity being attributed to the presence of sesquiterpene lactones (Liang 2007a; Taylor & Towers 1998; Taylor 1996). Antibacterial thymol derivatives are also present (Liang 2007b). Moreover, the plant contains flavonoids that were linked to a potent anti-allergic effect, which helps to substantiate its use for treating asthma and nasal allergies (rhinitis, sinusitis). Extracts have also shown significant anti-inflammatory activity against pleural effusion in animal studies (Liu 2005; Qin 2005; Iwakami 1992). Diverse product patents have been based on these traditional uses of Centipeda minima and subsequent studies – not only for the treatment of allergic disorders and herpes, but also to heal bone fractures, to encourage hair growth, and as an anticancer agent. Its potential as a cosmetic include claims for the relief of itching skin problems and as an anti-ageing cream (Beattie 2009). Preliminary investigations have suggested that the cellular protective effects of Centipeda minima may extend to the prevention of renal tissue damage (Sohn

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2009). There are also a number of studies into the anticancer (anti-tumour, antimutagenic, antiproliferative) potential of the herb and various components, including sesquiterpene lactones and a stilbene. In particular, 6-O-angeloylenolin demonstrated activity against a range of cancer cell lines – while the essential oil had interesting anti-tumour potential against nasopharyngeal cancer cells (Su 2010, 2009; Ding 2009; Changlong 2008; Chabert 2006; Oh 2006; Lee & Lin 1988). Centipeda minima has an interesting history of clinical use for the treatment of a number of infectious and parasitic disorders, including malaria and amoebiasis. The herb has shown moderate experimental activity against Giardia intestinalis – investigations isolated brevilin A (a sesquiterpene lactone) as the anti-giardial component. Additionally, this compound had activity against Entamoeba histolytica (a causative agent of amoebiasis) and the malarial parasite, Plasmodium falciparum (Yu 1994). Other components of pharmacological value in the herb include thymol derivatives, sesquiterpenes and sterols (Liang 2007a, 2007b; Wu 1991, 1985). The latter two classes of chemicals featured in Centipeda extracts with molluscicidal activity against a small tropical freshwater snail (Oncomelania hupensis), which acts as a host for the Schistosoma parasite (Zhao 2010; Ni 2009).

Centipeda contains chemicals active against the tropical freshwater snail Oncomelania hupensis. (Courtesy Qin Ping Zhao. Department of Parasitology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei Province, China)

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Headache Vines

Clematis glycinoides. (Courtesy John Tann, flickr)

Clematis microphylla. (Courtesy Melburnian)

The genus Clematis (Ranunculaceae) is of interest as some species have an irritant reputation similar to the Sneezeweeds. A popular, although somewhat discomfiting, herbal remedy utilised the crushed aromatic leaves of the Headache Vine (Clematis glycinoides), a viney plant of the rainforest margins. The crumbled leaf releases an ammonia-like vapour, which can be inhaled to relieve headaches, although the results are somewhat dramatic. Apparently the fumes provoked such an incredibly painful reaction that the initial headache was quickly forgotten – substituted, instead, by an equally uncomfortable sensation of the head ‘exploding’, the eyes ‘watering’ and intense irritation of the nasal passages. Fortunately, the whole ordeal had a reputation for being effective, although it was probably often only used in an act of sheer desperation when nothing else would work. Even so, some authors have mentioned that there were times when the remedy was totally ineffective. This would appear to be due to the variability of the active constituents. Selwyn Everist (1981) commented: ‘I

have experienced personally both these irritant and analgesic effects but have found that only young leaves or mature leaves in vigorous sappy growth are effective. Prolonged rubbing of the crushed leaf can blister the palms of the hands.’ The latter is not so surprising as Clematis belongs to the Ranunculaceae (Buttercup family) – which is known for its acid and irritant properties. There are four species of Clematis in Australia, three of which are native – C. glycinoides, C. aristata and C. microphylla. Traveller’s Joy (Clematis vitalba) is an introduced garden ornamental in some regions. All are wiry climbing vines, producing sweetly-scented masses of white starry flowers – which can make them quite difficult to tell apart. The Small Clematis (C. microphylla) has a wider distribution than the Headache Vine (C. glycinoides, a rainforest species) and extends into southern temperate climates, preferring a drier habitat. Clematis aristata has a similar temperate distribution. The irritant properties of the Headache Vine were shared by the Small Clematis (Clematis microphylla). In 1931, JB Cleland recorded a few details regarding its practical use in the Medical Journal of Australia. A leaf poultice was employed as a counter-irritant: In the case of my informant, a middle-aged lady, the poultice had been applied for too long a time to a knee which was affected with chronic rheumatism. To make the poultice, the leaves were stripped from the stems and cut up. Enough boiling water was poured on to make the mass sodden, and the leaves were crushed to express the juice. A fairly thick poultice was made of the leaves and the juice and applied to the affected part. This was left on for seven minutes, whereas it should have been applied for not more than three. On removal, nothing was apparent except redness. Twelve hours later blisters were forming,


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Clematis vitalba. (Courtesy Michael Gasperl, Wikimedia Commons, CC-by-SA 3.0 Unported)

The juice of the Traveller’s Joy (Clematis vitalba), introduced into the nostrils, was once a common migraine and headache remedy – despite highly irritant side-effects that could damage the mucous membranes (Chiej 1988). It is interesting that indigenous medicine in Papua New Guinea employed a local species similarly. At Finschhafen the leaves of Clematis papuasica were crushed and inhaled to clear blocked nasal passages – as well as being used to treat colds in other regions of the country (Woodley 1991).

which were ruptured. The patient had to keep in bed for a week and the knee was painful for another ten days, but the rheumatism was much benefited.

It sounds like another method of pain relief that would only be used as a last resort. The irritant effects are present throughout the genus – with many species having a similar reputation across the world, including the European Traveller’s Joy (Clematis vitalba) and C. cirrhosa (Chiej 1988). Maude Grieve (1931) provided a rather graphic description of the use of the Upright Virgin’s Bower (Clematis recta) as a decongestant for sinus problems: ‘The leaves and flowers when bruised irritate the eyes and throat giving rise to a flow of tears and coughing; applied to the skin they produce inflammation and vesication, hence the name Flammula Jovis’. Various African herbs (e.g. Clematis brachiata, C. hirsuta and C. oweniae) were likewise used to induce sneezing to clear head colds or headaches. The Ronga even

Clematis, along with Mimulus and Impatiens, were the first three remedies that formed the basis of the Bach Flower Remedies. Clematis is one of the five basic components of Rescue Remedy. The feathery Clematis seeds appear to be ‘longing to be blown away and start again’ – so this remedy has an association with a scatterbrained, dreamy type of personality, or the ‘absent-minded professor’, a characteristic so often linked with great creative potential. (Image courtesy Tanakawho, Tokyo, Japan, Wikimedia Commons, CC-by-SA 2.0)

‘steamed’ patients suffering malaria and colds with Clematis oweniae boiled in hot water, as well as taking it as a tea. In Tanganyika Clematis hirsuta was often placed on heated stones ‘to facilitate volatilization’ (Watt & Breyer-Brandjwijk 1962). Fortunately, the acrid, burning taste characteristic of these plants was said to be ‘greatly diminished’ during storage – which seems to indicate the loss of an irritant essential oil component – and processing

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The Erect Clematis or Upright Virgin’s Bower (Clematis recta), like many of the genus, appears to have antimicrobial properties. It has been utilised for treating syphilis, cancerous sores, diverse other forms of ‘foul ulcers’, and as a diuretic or diaphoretic agent (Grieve 1931). (Image courtesy Nuuuuuuuuuuull, flickr)

Clematis recta (as Clematis erecta) from Edward Hamilton, Flora Homoeopathica, Illustrations and descriptions of the Medicinal Plants used as Homoeopathic Remedies, Leath & Ross, St Paul’s Churchyard, Oxford St, London, 1852.

methods such as drying or decocting could reduce their unpleasant effects. In 1830 the botanist CS Rafinesque recorded the following comments regarding American species of Clematis11: ‘Almost all species medicinal … The bark and blossoms acrid, raising blisters on the skin; a corrosive poison internally, loses the virulence by concoction [cooking] and desiccation’.

11 In American traditions the Virgin’s Bower (C. virgiana) leaf and flower infusion was used to relieve severe headaches (Lust 1974). ‘Pepper Vine’ (C. ligusticifolia) leaves (fresh leaf juice or dried herb) provided a decongestant snuff (Moerman 1986).

The genus Thalictrum (Ranunculaceae) has a very similar reputation to the Clematis herbs. In Indian medicine Thalictrum foliolosum12 yielded a snuff useful for clearing ‘the brain’ and for coryza (a congestive head cold), or applied locally as a toothache remedy. Traditionally, the root has been valued for chronic dyspepsia and other digestive problems (e.g. flatulence), visceral obstructions, jaundice, ophthalmia – and as a convalescent remedy following an acute illness (Kapoor 1990). (Image courtesy C Basset, asianflora.com) 12 This species contains the antimicrobial agent berberine, as well as isoquinoline alkaloids (thalictrine, palmatine, jetrorrhizine) (Kapoor 1990).


Clematis as Antibacterials and Diuretics

Western Clematis (Clematis ligusticifolia). (Upper image courtesy Chris Savastio, Jr.; lower image courtesy Arlene K. Schag, flickr)

The use of the Clematis genus as wound-healing This description is reminiscent both the antibacterial agents appears to be wellofknown to European and Chinese deployment the genus. many cultures. Constantine Samuel of Rafinesque In America the spicy of (among ‘Pepper other Vine’ (1830), an academic andleaves botanist (Clematis ligusticifolia) also of in Clematis demand. things), mentioned that were a number Thisanalgesic herb had analgesic reputation that led had andanantibacterial healing properties wider on usethe forflora pain relief: lotions were intohisitswritings of Northern America: applied to backaches, swollen legs or13arms, ‘The extract used for osteocopic pain , dose while 1 or were useful for oily easing rheumatic 2poultices grains; frictions of an liniment curepains. the Furthermore, leaf washand wasCl. utilised as aare healing itch. Our Cl. avirginica viorna also agentas for soresand orsudorific, boils forforboth man (e.g. used diuretic chronic syphilitic animals (Moerman 1986). … Bruisedsores) greenand leaves used by our empirics as Remarkably recommendations have been escharotic foerealsimilar ulcers, and detergent for other made for other species across the globe. In Africa sores.’ Clematis brachiata was used in the treatment of sexually transmitted diseases (including gonorrhoea and syphilis), while C. oweniae (root cooked with

13 A violent form of bone pain that is fixed at a specific location.

This description is reminiscent of both the European and Chinese deployment of the genus. In America the spicy leaves of ‘Pepper Vine’ (Clematis ligusticifolia) were also in demand. This herb had an analgesic reputation that led to its wider use for pain relief: lotions were applied to backaches, swollen legs or arms, while poultices were useful for easing rheumatic pains. Furthermore, a leaf wash was utilised as a healing agent for sores or boils for both man (e.g. syphilitic sores) and animals (Moerman 1986). Remarkably similar recommendations have been made for other species across the globe. In Africa Clematis brachiata was used in the treatment of sexually transmitted diseases (including gonorrhoea and syphilis), while C. oweniae (root cooked with salt and nut oil from Trichilia roka) provided a remedy for thrush and coughs. Clematis hirsuta or C. sinensis poultices were also applied locally to ‘draw’ septic lesions (Watt & Breyer-Brandwijk 1962). Clematis hirsuta has shown ‘pronounced antifungal activity’ against Candida albicans and a number of common skin fungi (Cos 2002). An interesting Central American study of the anti-gonorrhoeal potential of Guatemalan plants noted that Clematis dioica was effective against various strains of the gonorrhoea bacterium (Neisseria gonorrhoeae) (Caceres 1995). The efficacy of some species in urinary tract disorders may well have influenced their use in venereal disease. Clematis recta was used as a diuretic and diaphoretic in Europe (Grieve 1931), while the Himalayan C. montana was recommended for urination problems (pain and excessive discharge) in China – as well as having a sedative effect useful for insomnia or restlessness (Chin & Keng 1990). Diverse other species have antimicrobial potential. In Cypriot traditions Clematis cirrhosa provided a leprosy remedy, the leaves (crushed or powdered) applied externally – as well as being useful for irritant skin diseases such as psoriasis and dermatitis (Georgiades 1987). The leaves of Clematis papuasica in Papua New Guinea were utilised for treating skin infections and appear to have effective antifungal activity – with studies showing a wide spectrum of antimicrobial properties for leaf and stem-bark extracts (Khan 2001, Woodley 1991).

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An Aromatic Irritant: Tickweed (Cleome viscosa)

Clematis flammula has been used for dropsy (to reduce oedema) in Turkey (Yesilada 1997). (Image courtesy Jean-François Gaffard, CC-by-SA)

Chinese Clematis Root (primarily sourced from Clematis chinensis14) provides an illustration of the varied scope of these plants in traditional medicine. The herb has an excellent reputation as an antirheumatic and analgesic – as well as possessing substantial anti-inflammatory properties for treating conditions as diverse as hepatitis, tonsillitis, laryngitis, skin and breast inflammation, and the parasitic disease filariasis. Investigations have supported the therapeutic effects of the remedy: hypotensive, anti-diuretic, anti-inflammatory, antispasmodic, sedative, antibacterial, anti-malarial, antitumour and hypoglycaemic (blood sugar-lowering) properties. Combined with vinegar and brown sugar it also had an unusual reputation for softening fish bones lodged in the throat. One study of 104 cases of fish bone impaction that were treated with this herb recorded an 85 per cent success rate (Li 2003; Wei 1991; Chiu 1988; Yeung 1985; Bensky & Gamble 1986).

14 Other resources include C. hexapetala, C. armandi, C. uncinata, C. meyeniana, C. henryi, C. finetiana, C. manshurica and C. paniculata (Yen 1992).

The genus Cleome (Cleomaceae family)15 is well represented in Australia – with around 20 species that are primarily found in the Northern Territory and Western Australia. They are commonly known as ‘spiderflowers’ due to their spider-like blossoms. Of these, the Yellow Spiderflower or Tickweed, Cleome viscosa, is a well-known medicinal herb that is found throughout the world’s tropics. It has a wide distribution throughout most of mainland Australia – although it does not extend to New South Wales and Victoria. (Upper image courtesy Smithsonian Institution, Plant Image Collection, United States Virgin Islands, Saint John, Cruz Bay Quarter; lower image courtesy Jeevan Jose) 15 While Cleome is usually placed in the Cleomaceae (along with the genera Cleomella, Gyandropsis and Physostemon), it was formerly classified in the Caper family (Capparaceae).


Cleome viscosa is a highly aromatic weedy herb. Although it is not botanically related to Clematis, it has a very similar reputation. Aboriginal people used the mashed plant as a poultice for rheumatism, swellings, ulcers, open sores, headaches and for treating colds (Isaacs 1994; Barr 1993, 1988; Webb 1969). It has an equally extensive medicinal reputation in Indian traditions, where the leaves were utilised to relieve headache, joint pain and innumerable types of skin infection. An ointment (leaves boiled in ghee) has been considered useful for wounds, or the leaf simply applied directly to ulcers, snake bites and scorpion stings. The warmed leaf juice provided a readily available remedy for earache or deafness, and could be used as an eye wash. The seeds have been widely utilised for skin diseases, as well as for fevers, diarrhoea, convulsions, and as a vermifuge.16 The seed powder was also taken internally as a remedy for haemorrhoids. The anthelmintic properties of the root and seeds were widely utilised in countries as diverse as Southeast Asia, India, China, Taiwan, Guam, the Philippines, the United States and Africa for intestinal worm infestations. The roots and seeds also provided a cardiac stimulant in Sri Lanka – while in Israel the plant was employed as an antidiabetic remedy (Mali 2010; Katewa & Galav 2005; Lassak & McCarthy 1992; Quisumbing 1951). In many places the aromatic leaves have simply been rubbed in the hands and used as a form of ‘smelling salts’ for sinus congestion or headaches. Cleome droserifolia and C. gynandra have a very similar reputation. Tickweed leaf poultices (mashed with salt) were also widely applied to ease pain such as an aching back or for headache. In the Philippines the herb also provided a useful wash for maggot-infested wounds (Burkill 1985; Perry & Metzger 1980; Satyavati 1976; Quisumbing 1951). In Southeast Asia, Tickweed has been used as a counter-irritant (for a local stimulant effect) – providing a deliberate blistering agent similar to that of a mustard poultice. Bailey (1880) noted: ‘it is used by the natives to relieve headache. It is used in Cochin China as a counter-irritant in the same way as sinapin [extract of black mustard seeds] is in Europe, and also as a vesicant. In the United States the roots 16 Cleome gynandra had a similar reputation. In India a cupful of root extract, mixed in coconut milk with honey (1–2 teaspoons), has been given to children below twelve years age twice a day for 5–6 days to expel intestinal worms (Salave 2011).

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are said to be used as a vermifuge’. Similar uses have been recorded from India and the Philippines. Dr Kirtikar, in Notes on Some Indian Drugs, referred to an exhibit of the seed oil at the Intercolonial Congress of 1882, held in Melbourne: ‘The plant has a great reputation as a remedy for chronic ororrhoea [ear infection]. Its action is chiefly antiseptic, as it contains a powerful volatile principle not unlike in smell to that of the mustard. This active principle has besides stimulating properties. The plant is highly viscous in every part, and is covered over with hairs, which are capped with a sticky gland and smell powerfully.’ The plant (herb, fresh leaves or the seeds) also had a reputation as a mustard substitute. This stimulating effect was due to pungent mustard oil components, which also have antibacterial properties17 (Oliver-Bever 1986). They possibly include sinapine, which is the compound that gives mustard its ‘biting’ flavour. However, as these are volatile components, the plant loses its vesicant and acrid properties upon dessication or heat exposure (Burkill 1985; Satyavati 1976). Investigations have confirmed that Cleome viscosa extracts have a wide range of pharmacological properties: analgesic (whole plant, seeds); anthelmintic and hepatoprotective (seeds); antidiarrhoeal, antipyretic (plant; comparable to paracetamol), and anti-inflammatory (whole plant); immunemodulatory (aerial parts); gastroprotective and anti-Helicobacter (leaves). Extracts have also shown antioxidant and anticancer potential (Mishra 2011; Mali 2010). Furthermore, the plant has potent broadspectrum antimicrobial (antibacterial, antifungal, mycotoxic) activity, as well as wound-healing properties that would support its use in wound and ulcer healing, including treatments for leprosy (Bose 2011; Koppula 2011; Panduraju 2011; Wake 2011; Mali 2010; Silue 2009; Parimaladevi 2003).

17 Mustard oil glucosides (glucosinolates) are important biological components of the Brassicaceae family. Spider plants (herb) contain glucosinolates (e.g. methylglucosinolate, cleomin, glucocapparin) that yield isothiocyanates with strong antimicrobial properties (Silue 2009; Mari 1993; Drobnica 1976). Glucosinolates have also attracted a lot of research interest as dietary anticancer compounds from vegetables such as broccoli and cabbage. This may be linked to the use of the Spiderflower plant as an antitumour application to skin growths.

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The use of Tickweed leaf smoke as a mosquito repellent inspired investigations that found extracts had good larvicidal activity against the malaria mosquito vector Anopheles stephensi – larva is pictured here (Saxena 2000). Seed extracts of Cleome viscosa have traditionally been utilised as an anthelmintic and febrifuge, while the leaves (juice) were specifically recommended for malaria (Mali 2010) – which suggest good antiparasitic potential. In Africa root decoctions of Cleome gynandra have been similarly utilised for treating feverish conditions, including malaria (Fowler 2006) – a use that has been substantiated by studies showing the plant has antimalarial activity against Plasmodium falciparum (Gessler 1994). (Image courtesy CDC USA)

The reputation of these plants as a tick repellent appears to be well justified. Cleome gynandra leaves have repellent and acaricidal effects that were most pronounced on nymphs, with less activity on adult ticks. Even so, observations in the field indicated that the area 2–5 metres around stands of these plants were tick free – which suggested its use in tick-management schemes for farming purposes (Malonza 1992). Evaluation of the essential oil has identified a number of components with effective anti-tick properties (Anbazhagi 2009). Cleome gynandra extracts have also shown activity against red spider mite, diamondback moths, aphids and thrips – which suggest additional active pest-deterrent uses intercropped with vegetables such as tomatoes and cabbages, or for the cut flower trade, particularly roses. Glucosinolates in the leaves (which impart a bitter taste) may contribute to its insecticidal properties (Silue 2009; Nyalala & Grout 2007). There are various uses of Cleome viscosa that suggest an influence on hormonal function. In Papua New Guinea the leaf has been taken as a fertilityenhancing agent (sometimes chewed with betel nut) – with a similar use being recorded for Cleome gynandra in Nigeria and Uganda. Indeed, in Africa this species

Cleome hassleriana. This species has strong antifungal activity against soil-borne pathogens due to its glucosinolate components (glucocapparin, glucocleomin). Importantly, the overall microbial balance of the soil was not adversely affected. This has even led to the suggestion for its use as a green manure that could replace the pesticidal toxin methyl bromide (Lazzeri & Manici 2001; Lazzeri 1998). (Image courtesy Schoinard, Wikimedia Commons, CC-by-SA 3.0 Unported)

is widely recommended as a tonic vegetable during pregnancy which would help facilitate labour and postpartum recovery (Mishra 2011; WHO 2009; Okoli 2007). In Uganda the root decoction was traditionally utilised for the prevention of miscarriage or to hasten childbirth (induce uterine contractions), help remove the afterbirth (including complications with a retained placenta), and to control bleeding following the birth. Studies have shown that root extracts had a weak uterine stimulant effect that could promote the effects of oxytocin during childbirth. Extracts (roots, leaves and flowers) have also been taken to enhance male potency (sexual impotence, erectile dysfunction) (Kamatenesi-Mugisha 2005; Kamatenesi-Mugisha & Oryem-Origa 2005). However, there is evidence that the use of Cleome viscosa can actually reduce the sperm count (Oladele & Abatan 2010).


The hepatoprotective properties of seed and leaf extracts of Tickweed are significant, which support its traditional use in the treatment of jaundice. Its effects were found comparable to the premier liver remedy Milk Thistle (Silybum marianum) – and, similar to this herb, Tickweed seed extracts were rich in flavonoids (Mobiya 2010; Gupta & Dixit 2009). Coumarinolignoids (cleomiscosins) from the seeds were identified as highly active hepatoprotective, antiinflammatory and immunomodulatory components (Yadav 2010; Bawankule 2008). A couple of related species with liver-protective potential are Cleome droserifolia and, possibly, C. gynandra, which has been utilised for treating bilious disorders (AbdelKader 2009; Anbazhagi 2009). In addition, Cleome droserifolia has a particularly good reputation as an antidiabetic agent, with potential anti-obesity and cholesterol lowering attributes – although further toxicological evaluation has been recommended (ElKhawaga 2010; Emam 2010; Bnouham 2006).

good reputation as an anti-inflammatory and analgesic agent – as well as being antidotal for scorpion stings. Extracts have shown notable immune-suppressive effects which were linked to an anti-inflammatory activity (Kori 2009). Spiderflower is a useful green vegetable that contains fairly high amounts of β-carotene and vitamin C – as well as moderate amounts of calcium, magnesium and iron. Vegetables often lose vitamin C during the cooking process (losses are usually between 50–90%, sometimes higher) although, in comparison to many other greens, Cleome leaves generally retain good levels (a low level of vitamin C loss: 5–18%) (Seeramulu 1983).

Cleome gynandra

Cleome gynandra, from Francisco Manuel Blanco, Flora de Filipinas, Gran edicion, Manila, 1880–83.

The Spiderflower Cleome gynandra (syn. Gynandropsis gynandra) is naturalised throughout Queensland, and in a few places in the Northern Territory. (Image courtesy Kim & Forest Starr, Hawaii)

Cleome gynandra is a pretty species with a weedy habit that is often found on waste lands and rubbish dumps. Medicinally, the herb has a

Cleome gynandra seeds. (Courtesy Steve Hurst, UDSA)

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Cleome viscosa seed oil, which is edible, contains a high proportion of polyunsaturated fatty acids (oleic 18.6%; linoleic 32.8%; linolenic 26.6%) in comparison to saturated fatty acids (palmitic 2%; stearic 20%) (Rukmini 1978) – although the analysis provided by a later study suggests the levels of polyunsaturated fatty acids could be somewhat higher (linoleic 70%, oleic 14%), with an associated reduction in the proportion of saturated fatty acids (palmitic 10%; stearic 5%). Volatile components are also present (Mishra 2010). The use of the crushed seed as a folk medicine for treating infantile convulsions and mental disorders suggests that the remedy may affect nervous system function, with investigations showing extracts had anticonvulsant properties (Mishra 2010; Nadkararni & Nadkarani 1992). (Image courtesy Ming-I Weng, Taiwan)

Cleome rutidosperma is naturalised in the Northern Territory and Christmas Island. Extracts of the whole plant possess antioxidant, anti-inflammatory, anti-arthritic, antipyretic and analgesic properties. In addition, the herb has demonstrated anthelmintic, laxative, diuretic and antimicrobial activity (Chakraborty 2010; Chakraborty & Roy 2010; Bose 2007). (Image courtesy Jeevan Jose, Wikipedia)

The roots of Cleome rutidosperma have an interesting medicinal reputation for the treatment of paralysis, epilepsy, convulsions, spasm and as an analgesic for pain relief (Chakraborty & Roy 2010). (Image courtesy Albert, Wikimedia Commons, CC-by-SA 3.0 Unported)

A Forgotten Herb: The Medicinal Pigweed Purslane can be counted among the most underutilised and undervalued of the Australian native herbs. It has an ancient history of use across the globe, although

Pigweed or Purslane is a heat and drought tolerant plant that is found throughout the Australian continent. It has an excellent reputation as an antiscorbutic that once led to its recommendation for the treatment of scurvy. The succulent leaves and stems have been a prized Aboriginal food item. The plant was collected, piled in heaps and left to dry – which allowed the seed capsules to ripen: ‘The seeds, after washing, were ground between stones and consumed raw. They are highly nutritious and keep the native in excellent condition’ (MacPherson 1930). (Image courtesy Ton Rulkens)


Bee on Portulaca bicolor. Australia has an interesting diversity of Portulaca species, with around 23 being considered native – and an additional naturalised ornamental, Portulaca grandiflora. At least eight of the native species have not yet been botanically classified. (Image courtesy Craig Nieminski, flickr)

in many places it has been relegated to little more than a useless weed – which is even becoming locally endangered due to this misconception. It is a fairly unassuming-looking vegetable with gel-like qualities that are due to an arabinoglycan gum with emulsification properties similar to gum arabic. It can thus be effectively added to soups and stews as a thickening agent. This suggests diverse culinary and food processing uses for the plant – particularly as it has significant antioxidant and antimicrobial attributes (Irawan 2003). Purslane is also highly underestimated as a nutritional and medicinal resource. It is a good source of carbohydrate (40.7%), protein (23.5%) and fibre (8%), and is rich in vitamin C (ascorbic acid), β-carotene and B vitamins (particularly B1, B2 and folic acid). Vitamin E levels can be significant (ɑ-tocopherol 230 mg/g dry weight) and β-carotene levels in the leaves are also quite high (22–30 mg/g). Purslane has an extremely useful dietary fatty acid content (5.3%; 8.5 mg fatty acid per g net weight) that contributes omega-3 fatty acids, notably ɑ-linolenic acid (Aberoumand 2009; Xin 2008; Simopoulos 2004; Liu 2000). In comparison with other green leafy vegetables (mg/g), Purslane’s overall fatty acid level is high – for example, Spinach (1.7 mg), Buttercrunch Lettuce (0.6 mg), Red Leaf Lettuce (0.7 mg), Mustard greens (1.1 mg) (Simopoulos 2004). Australian studies have determined the following total fatty acid content for Purslane: fresh leaves (1.5–2.5 mg/g), stems (0.6–0.9 mg/g) and seeds (80–170

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mg/g). ɑ-linolenic acid was present at high levels (% total fatty acid content) in the leaves (60%) and seeds (40%) (Liu 2000). Purslane has the potential to be a very good mineral resource (mg/100 g) (Brand Miller 1993): • The whole plant is low in sodium, with higher levels of potassium (709–940 mg), magnesium (206–266 mg) and calcium (97–112 mg). • The root can have a much higher potassium content (1170 mg), with fair to good levels of magnesium (61 mg) and calcium (382 mg). • Therefore, while a damper (bread) preparation would be low in sodium, the level of other minerals can be quite good: potassium, magnesium, calcium – as well as being high in iron (13–15 mg) and zinc (3–5 mg), and a low amount of copper. It is worth noting that the leaf and seed paste • can be exceptionally high in iron (54 and 64 mg, respectively). There are a couple of other points of interest with regard to freeze-dried Purslane (Ward 2009): • A freeze-dried product retains good levels of protein and dietary fibre, with a low total fat content. • The caffeic acid content can be high – 2,632 mcg (mcg/g freeze-dried Purslane). • Ferulic acid (826 mcg) is present in good amounts, as are some other phenolics: quercetin (191.2 mcg), kaempferol (153.5 mcg), cyanidin (246.5 mcg).

In comparison with Purslane, Portulaca pilosa can be equally high in iron (5.5–38 mg) and potassium (500–1000 mg); with reasonable amounts of sodium (50–120 mg), magnesium (170–300 mg), calcium (265–300 mg) and some zinc (1– 1.7 mg) (Image courtesy Kim & Forest Starr, Hawaii)

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Purslane seeds. (Courtesy University of Missouri Extension)

The Sea Purslane (Sesuvium portulacastrum), which has an anti-scurvy reputation, has a very similar appearance to that of Portulaca pilosa – although the flowers tend to be a lighter lilac and it is restricted to seaside habitats (Images courtesy Kim & Forest Starr, Hawaii)

Purslane has been utilised for a remarkable variety of conditions: • urinary tract disorders (dysuria, gonorrhoea, haematuria, dysuria, diuretic, urinary antiseptic); • inflammatory problems (mastitis, impetigo, erysipelas, eye inflammation); • infectious respiratory disorders (tuberculosis, whooping cough); • intestinal distress (gastritis, colitis, dysentery, worms); • as an effective healing antimicrobial agent (swelling, scalds, bruising, abscess, boils).

Many of these recommendations have been supported by studies that show a wide range of pharmacological attributes. Extracts of the herb have significant antiinflammatory, analgesic, antimicrobial, and wound healing properties.18 It also contains components that are active against schistosomiasis and leishmaniasis parasites19 (Dkhil 2011b; Irawan 2003). The antiparasitic properties of the plant could also be useful for treating intestinal worms (Quinlan 2002). In addition, extracts have shown a gastroprotective effect that would support the use of the remedy in stomach ulceration (Karimi 2004). The herb itself has a complex chemistry with diverse components being present.20 Purslane’s phenolic content (586 mg/100 g) can be associated with good antioxidant activity, which supports many of its medicinal uses (Yang 2009; Aberoumand 2008). Extracts have shown anti-inflammatory, renoprotective and hepatoprotective properties against drug-induced cellular damage that were linked with an antioxidant effect. It has shown interesting protective potential against liver damage due to the anticancer drug cisplatin. Indeed, the hepatoprotective activity of the herb extract was significant – and it has been utilised for treating viral hepatitis in China (Sudhakar 2010; Amida 2010; Al-Howiriny 2008; Elkhayat 18 Purslane contains the wound-healing agent allantoin and studies on the fresh plant have shown good wound-healing effects (Rashed 2004). Allantoin is an active ingredient of the wound-healing herb Comfrey (Symphytum officinale). 19 Other species of Portulaca also appear to have antiparasitic potential. P. hirsutissima and P. werdermannii have shown activity against Leishmania amazonensis, as well as immunomodulatory activity (Costa 2007). 20 Alkaloids, coumarins, organic acids (cinnamic, caffeic, malic and citric acids), anthraquinones, flavonoids (kaempferol, apigenin, myricetin, quercetin, luteolin), saponins, tannin, glutathione, glutamic and aspartic acids (see Rashed 2004 and Dweck 2001 for details).


2008; Wang 2007). Polysaccharides are among the active components of Purslane extracts with antiviral (anti-herpes virus), immune-supportive, anti-stress and antioxidant activities. Interestingly, the herb can also improve exercise tolerance levels (Xiaojuan 2011; Dong 2010; YouGuo 2009). Additionally, Purslane has a reputation as a tonic in cardiovascular disorders including hypotension, palpitations and cardiac weakness21 (Irawan 2003). It has been suggested that the dietary use of Purslane could even be associated with a lower risk of heart disease and cancer due to its omega-3 fatty acid content – which would also be linked to an antiinflammatory effect. This, combined with the herb’s cholesterol-lowering potential and the presence of cardioactive glycosides and norepinephrine (i.e. noradrenaline, which has hypotensive effects) suggest further benefits for the cardiovascular system (Dkhil 2011b; Karimi 2010; Sanja 2009; Movahedian 2007; Simopoulos 2004; Ayodele 2005). Polysaccharide-based Purslane extracts have demonstrated significant antidiabetic activity (Gong 2009). The herb modulates cellular sensitivity to insulin, reduces glucose absorption and increases cellular glucose uptake. Clinical trials gave good responses, with the herb being marketed as an adjunct to antidiabetic therapy (Nutrition Care 2006). The woundhealing properties of Purslane may also be useful in counteracting the impaired healing responses of diabetic individuals (Laitiff 2010; Rashed 2003). (Image courtesy Nutrition Care, Australia) Aloe vera has a similar mucilaginous character to Purslane. It also has hypoglycaemic properties and good woundhealing effects, with significant potential benefits for diabetic individuals (Chithra 1998). (Image courtesy Solara Antara, flowersforhealing.com) 21 Levartenol, which is present in leaf extracts, has shown cardiotonic activity, leading to more vigorous contractions of the heart muscle. This compound can raise blood pressure and lower the heart rate (Dweck 2001)

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Purslane has long been used as a remedy for respiratory disorders, with studies confirming significant muscle-relaxant effects, with aqueous extracts possessing activity equivalent to that of the anti-asthmatic drug theophylline. These findings, plus its anti-inflammatory and antioxidant properties, support the traditional use of the decoction (boiled plant extract) as a bronchodilatory for asthmatic individuals – which has verified by clinical studies (Boskabady 2004; Malek 2004; Habtemariam 1993; Parry 1993, 1988, 1987; Okwuasaba 1986). In addition, the herb has antitussive properties (i.e. reduces the incidence of coughing) which were comparable to codeine (Boroushakei 2004). Purslane possesses substantial antimicrobial attributes that would complement its significant healing reputation: • Plant extracts have good antifungal activity against dermatophytes (Trichophyton spp.) that are responsible for fungal skin infections (Oh 2000). • The herb has good clinical activity in a fungal condition of the mouth known as oral lichen planus (the term ‘lichen’ referring to the lichen-like appearance of the infected area) (Agha-Hosseini 2010). • Seed extracts demonstrated a high level of antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Pseudomonas aeruginosa, comparable to gentamicin. However, this activity appears to be quite specific as extracts had a low level of activity against Candida albicans and were inactive against Escherichia coli, Proteus vulgaris, Salmonella typhi and Aspergillus niger. • Other studies indicate that extracts can have a high level of activity against food-borne pathogens such as Staphylococcus aureus and Shigella dysenteriae. This supports numerous other traditional uses of Purslane, including its use as an antidiarrhoeal, antiphlogistic (anti-inflammatory) and bactericide for bacillary dysentery (Bae 2004; Yagoub 2006). The antibacterial properties of Purslane have also seen it recommended for the treatment of gonorrhoea (Dweck 2001). Various studies have shown that Purslane can affect the genitourinary system and fertility, including an inhibitory effect on male sperm formation. There is an extremely interesting clinical report regarding the

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efficacy of the seed powder for treating abnormal uterine bleeding conditions such as excessive menstrual bleeding and peri-menopausal bleeding (Shobeiri 2009; Verma 1982). Purslane extracts also possess anxiolytic, sedative and anticonvulsant properties. Herb extracts, as well as betacyanin components, have demonstrated substantial neuroprotective effects with potential benefits for memory function (Wang & Yang 2010; Chen 2009; Shobeiri 2009; Hongxing 2007; Wang 2007). Portulaca quadrifida is another medicinal species with an influence on central nervous system function with anticonvulsant properties. Extracts could facilitate recovery from seizures, as well as possessing sedative, analgesic and antifungal potential (Kamil 2010).

Pigweed Pigments Portulaca grandiflora is a colourful garden ornamental with a very interesting history. The famous botanist William Jackson Hooker was the first to describe Portulaca grandiflora in 1829 after a South American excursion to the Rio Desaguardero. He admired ‘the rich purple hue, here and there marked with spots of an orange colour, from the orange-coloured variety which grew intermixed with the other’. Different varieties of the herb express specific amounts of betacyanin and betaxanthin pigments (betalains), with colours ranging from yellow and orange, to red and violet. White signifies an absence of pigmentation (Gerritson 2000). The yellow colour of Portulaca oleracea flowers is due to dopamine-betaxanthin (miraxanthin V), a pigment with fluorescent properties (GandíaHerrero 2009, 2005). Betalains are a relatively unusual class of pigments that replace the more common anthocyanin phenolics. Flavonoids are commonly associated with flower colours, as well as colour variations in leaves, fruit and seeds. Betalains differ chemically and are of particular interest as food colourings – they have even been added to red wine to enhance its appearance. The most familiar is the rich burgundy pigment in beetroot, which belongs to the botanical order Caryophyllales – as do diverse other betalain-containing plants

Medicinally, Portulaca grandiflora, which is considered naturalised in Australia, has been utilised as a detoxicant herb for the relief of sore throat and skin rashes. Extracts have shown significant antimutagenic properties (Sriwanthana 2007; Liu 1990).

including spinach, cacti and Bougainvillea. Even the brightly coloured Amanita toadstools belong to this classification (Brockington 2011; Christinet 2004; Gerritson 2000).


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Buckthorn: A Native Source of Aesculin

Bursaria spinosa in flower. (Courtesy Brian Walters)

Amanita muscaria, the Fly Agaric, is a distinctly decorative fungus that contains a complex array of colouring substances that include betaxanthins, betacyanins, muscaflavins and seco-dopas. Among them are specific pigments for yellow (muscaflavin), red (muscarubrin), and red–purple (muscapurpurin) (Stintzing & Schliemann 2007).

The native Australian Buckthorn (Bursaria spinosa) is a small spiny endemic tree that is variously known as the Native Box, Box-thorn and Native Olive. The nectar-rich flower clusters can be used as a sweet bush snack. There are seven native species. Of these, Bursaria spinosa is found throughout much of the country – with the exception of Western Australia and the Northern Territory, where B. occidentalis is predominant. Queensland species include Bursaria incana and B. tenuifolia. Bursaria spinosa has two

Portulaca for Phytoremediation

Portulaca oleracea. (Courtesy Kim and Forest Starr, Hawaii)

Purslane is a good candidate for the revegetation of harsh drought-prone and saline environments. Indeed, the herb will remove and concentrate sodium and chloride from the soil, thereby having a substantial remedial effect (Hamidov 2007). In addition, Portulaca oleracea and P. tuberosa have metal-accumulation attributes (particularly for cadmium, chromium and arsenic) that suggest these species would be good choices for remediation of effluent-contaminated sites – surviving conditions that would seriously hamper the viability of many other plant species (Tiwari 2008). Purslane also has a good ability to remove bisphenol A (BPA) from water supplies. This compound, which has been in widespread use for the manufacture of plastics (PVC) and synthetic resins, has endocrine-disrupting properties that result in an oestrogenic effect. In a study of over 100 common garden plants, Purslane showed the best activity for quickly removing BPA from contaminated water. It may well be equally useful for phytoremediation involving other phenol-based endocrinedisrupting agents such as the steroid hormone oestradiol, and 2,4-dichlorophenol (an intermediate in the production of the herbicide 2,4-D) (Imai 2007).

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subspecies (lasiophylla and spinosa) that are found in southern Queensland, ranging to the more temperate climates of New South Wales, South Australia, Victoria and Tasmania. New South Wales has a couple of unique species – Bursaria longisepala from the Blue Mountains, and B. calciocola from the Wombeyan Caves Reserve. In addition, there is a rare species in central Queensland, Bursaria reevesii, which is restricted to only two sites.

Horsechestnut (Aesculus hippocastanum). However, this does not mean that local Australian resources should be simply discarded – particularly a product that has such excellent market potential.

Ripe horsechesnut conkers. Horsechestnut seed extract has traditionally been regarded as a valuable ‘tonic’ astringent and there is a substantial amount of support for this recommendation. The remedy has a significant strengthening effect on the venous system. The active principle is a complex of around 30 individual compounds (triterpene oligoglycosides) that form a saponin-based mixture usually referred to as aescin, with 3–6 per cent present in the seed, as well as flavonoids and lipids. In much of the older literature this mixture was known as aesculetin (the glucoside of which is aesculin, also spelt esculin). However, most recent studies have utilised Horsechestnut extracts (HCE), standardised to contain around 70 per cent aescin (escin) (Sirtori 2001). This is an important distinction because the terms utilised in this work are as per the original papers. (Image courtesy Bob Gibbons/Arkive)

Early investigations into the chemistry of Buckthorn Bursaria occidentalis. (Courtesy Bernhard Jacobi, flickr)

Buckthorn is illustrative of an Australian native plant with great medicinal potential, but little backing for practical development. Despite the fact that the tree has generally been regarded as a nuisance and a weed, Buckthorn has worthy potential as a natural product resource. It contains a saponin-based substance named aesculin (or esculin) that is particularly useful for venous circulatory problems such varicose veins and haemorrhoids. In 1980 a Sydney company began the export of aesculin extracted from Buckthorn to Europe. Three years later the venture collapsed. Unfortunately, the price of the product was not competitive enough against the yield of the European

determined that: ‘Very little aesculin is found in the twigs and branches, but from the leaves 4 to 5% of the compound may be obtained. Most of the commercial supply of aesculin seems to come from NSW, whence small amounts are exported. Through its ability to absorb strongly in the ultra-violet region, aesculin is commonly employed in preparations designed to protect the skin from sunburn. Another use of aesculin is as a test-substance in microbiology where certain organisms are identified by their ability to break down the substance’ (McKern 1960). Aesculin has also been utilised for the treatment of an ulcerous autoimmune skin condition known as lupus. In 1949 Dr Nancy Atkinson demonstrated Bursaria leaves had antibiotic properties which were active against Staphylococcus aureus.


Professor EH Rennie originally discovered that aesculin was present in Buckthorn in 1889. At that time, the apparent ability of the leaves to impart a distinctive blue colour to the Blue Lake had attracted a fair amount of curious enquiry: Those of us who hail from South Australia are familiar with the description of the Blue Lake near Mt. Gambier. On the bank of the lake, as well as in many other parts of South Australia, there is an abundant growth of a shrub known as Bursaria spinosa, Pittosporaceae, the leaves of which if placed in water communicate to it a blue fluorescence, and it has been suggested that the lake owes its blue colour to the leaves which fall into it. I doubt very much whether that is the true explanation, but, be that as it may, I have been able to show that the leaves contain a well-known glucoside, aesculin, occurring in the bark of the horse-chestnut, and which imparts a blue fluorescence to water (Rennie 1926).

Blue Lake mid-December. The Blue Lake is around 75 metres deep and fills an extinct volcanic crater. The water changes colour from grey to a vivid blue in November, gradually fading to a winter grey by mid-year. The explanation lies in chemical changes involving the formation of microcrystals of calcium carbonate during the warmer weather. This has an effect on light penetration and diffraction in the water that result in scattering the blue light wavelength. In addition, microscopic organisms that may exert an influence on the colour scheme are present. (Image courtesy Aaron Allen)

The saponin mixture aescin (or escin) has a range of valuable medicinal attributes. Recent literature differentiates between ɑ-aescin and β-aescin, with β-aescin considered to be the pharmacologically active component. Studies have shown antiviral, antioxidant, anti-inflammatory, anti-oedema, immunosuppressive, and analgesic properties – as well as protective effects in some forms of gastric ulceration and liver damage. In addition, investigations have indicated interesting

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anti-arteriosclerotic, radioprotective, neuroprotective and anticancer potential (Li 2012; Atmaca 2011; Ji 2011; Jiang 2011; Lee 2011a, 2011b; Murat Bilgin 2011; Tien 2011; Yun 2011; Rios 2010; Barber 2009; Yalinkilic & Enginar 2008; Zhao 2008; Lee 2002; Sirtori 2001; Lin 2000; Gilani 1998; Martin-Aragon 1998; Matsuda 1997; Galabov 1996; Martin 1991; Kabelitz & Al-Gorany 1989; Tubaro 1988). Horsechestnut seeds are a major source of aescin saponins. The remedy has traditionally been utilised as a tonic for venous problems, including haemorrhoids. Research has verified many of its traditional recommendations – an ever-expanding body of knowledge that continues to suggest far wider clinical applications with rather remarkable potential. There are numerous clinical studies that support the use of Horsechestnut seed extracts in chronic venous insufficiency (Altern Med Rev 2009; Leach 2006; Suter 2006; Dickson 2004, Pittler & Ernst 2004, 1998). Not only is the inherent anti-inflammatory effect of the remedy extremely useful, there are cartilageprotective properties that help to facilitate the healing process in traumatic injury. A number of proposals have therefore examined its potential benefits in osteoarthritis and rheumatoid arthritis (Elliott 2001; Watanabe 1999; Yamada 1999). Aescin may even have a synergistic anti-inflammatory effect in combination with corticosteroids, thereby potentiating the drug’s clinical usefulness (Xin 2011a). Investigations into the biochemistry of the European Horsechestnut (Aesculus hippocastanum) have offered many new insights into the therapeutic value of aescin. This compound’s potential for the reduction of post-operative trauma is truly impressive: alleviating inflammation, oedema and tissue damage, promoting wound healing and reducing the incidence of adhesions. It has even demonstrated modification of ischaemic brain damage (Zhang 2011, 2010; Harikumar 2010; Wang 2009; Fujimura 2006a; Fu 2005). This protective effect on brain tissue may have more extensive benefits as aescin has shown neuroprotective effects against organophosphateinduced cerebral oedema (Wang 2011). Clinically, aescin injections have been utilised to minimise the traumatic effects of accidents resulting in severe head injuries and for the prevention of deep vein thrombosis following surgery – as well as possessing interesting vascular-protective properties suitable for

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use during heart surgery (angioplasty) to prevent tissue injury (Kwon 2011; Pan 2003; Sirtori 2001; Huang 1993). Additionally, Horsechestnut and aescin have been employed in the treatment of Bell’s palsy, dysmenorrhoea, carpal tunnel syndrome, back injuries and intervertebral disc lesions (Sirtori 2001; Morgan & Bone 1998). Esculetin has also been investigated for treating eye disorders due to ischaemia (reduced blood flow) and inflammation (Liu & Chiou 1996; Gupta 1993).

Indian Horsechestnut. In addition to the European Horsechestnut, other species of Aesculus can be utilised as aescin resources. Indeed, the content of the Indian Horsechestnut (A. indica) seeds (13.4% weight/weight [sic]) was higher than that of A. hippocastanum (9.5%) (Srijayanta 1999). A formulation of sodium aescinate has shown significant anti-inflammatory and antioxidant cellular-protectant effects against lung injury due to endotoxin exposure and methyl parathion (Du 2011; Xin 2011b). This extremely hazardous cholinerase-inhibitory insecticide was once widely used for agricultural crops, mainly rice, cotton and fruit trees. It has also been employed in chemical warfare – and is now banned in many countries. The product (pictured) was outlawed in Germany in 2002 and this bottle shows explicit warnings as to its toxicity. (Image courtesy Mr Checker, Wikimedia Commons, CC-by-SA 3.0 Unported)

There is good potential for aescin to assist recovery from paralytic ileus, a post-operative complication of abdominal surgery – as it was effective at helping to re-establish gastrointestinal mobility (Xie 2009). Other benefits for gastrointestinal disorders may be linked to an inhibitory effect on Escherichia coli survival in the gut, which supports its use as an antidiarrhoeal remedy. Studies have also suggested


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Horsechestnut: The Extraordinary Clinical Potential of a Traditional Venous Tonic

Horsechestnut: tree and flowers.

Sand flies of the genus Phlebotomus are very small bloodsucking insects that are vectors for parasitic diseases, including leishmaniasis. Aescin has anti-leishmanial properties that show clinical promise. Recent investigations have focused on effective drug delivery systems such as encapsulation of the saponin in colloidal carrier nanoparticles that maximise its efficacy (Van de Ven 2012a, 2012b, 2011). (Image courtesy World Health Organization, Geneva, Switzerland, and CDC, USA)

a beneficial role as an anti-inflammatory agent for treating colitis (Witaicenis 2010; Duncan 2004). More recently, the discovery of an antiobesity effect for esculetin has shown positive effects on cholesterol levels and fat absorption (Avci 2010; Shin 2010; Hu 2008). Another commercial avenue for the use of aescin involves the cosmetic industry. Its healing, anti-inflammatory and anti-oedema properties make it well suited for incorporation into a range of cosmetic formulations. Studies showing antioxidant, UV-protective, anti-melanoma and anti-ageing effects have added extra support for its use (Lee 2007; Fujimura 2006a, 2006b; Tahara 2005).

Horsechestnut’s highly effective anti-oedema and veno-protective activities can significantly ameliorate vascular damage. The remedy is particularly well suited for conditions where a slow, progressive venous tonic effect is required. Horsechestnut can therefore be beneficial for a wide range of disorders, ranging from chronic venous problems (varicose veins, lower limb oedema and haemorrhoids) to surgical wounds or injuries characterised by swelling and venous congestion. Clinical studies have verified that there can be substantial improvement in chronic venous insufficiency, with gradual resolution of pain, tiredness, tension, leg swelling, itching and oedema (Luzzi 2011; Altern Med Rev 2009; Pittler & Ernst 2004; Siebert 2002; Ottillinger & Greeske 2001; Morgan & Bone 1998).

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Horsechestnut has also been utilised for the treatment of asthma and bronchitis (Morgan & Bone 1998). The anti-inflammatory, bronchodilatory and expectorant effects of the remedy would certainly assist in relieving respiratory distress. Experimentally, β-aescin has shown potent lung-protective and anti-allergic attributes that can reduce airway inflammation (Xin 2011a; Lindner 2010; Mabalirajan 2009). In acute injuries, the local application of various preparations (wash, ointment or cream) has been used to resolve bruising and reduce tissue oedema (swelling). Therefore the remedy can be effective for treating sports injuries, dental surgery, gynaecological and obstetrical venous problems. However, it should not be applied to open wounds as there is a possibility that the saponins may be directly absorbed, which can result in gastrointestinal upset (Morgan & Bone 1998). Overall, the incidence of side-effects associated with the use of Horsechestnut seed preparations is extremely low. Refinements in the quality of aescin-containing extracts have resulted in a high degree of efficacy and they are extremely safe in clinical practice. One report examining over 900 million individual doses of a standardised extract revealed that only 15 patients complained of side-effects – an impressive safety record (Morgan & Bone 1998). There are, however, occasional reports of gastrointestinal discomfort, dizziness, headache and skin itching (Altern Med Rev 2009). This has been associated with the use of refined products, and is probably because modern manufacturing methods tend to produce products with a high level of purity that permit the use of quite high doses. Furthermore, a few incidents of anaphylactic (severe allergic) reactions due to the topical application of aescin are on record. There have been rare reports of poisoning with Horsechestnut seeds that were linked to the presence of a toxic principle called esculoside – which is now removed in the production of standardised extracts (Sirtori 2001). The anti-tumour potential of Horsechestnut is an interesting facet of the remedy that has been

evaluated by a number of studies. Esculetin is a strong antioxidant and antimutagenic agent that has shown anticancer activity in breast cancer cells. Studies have also suggested that a number of phenolic compounds (i.e. esculetin, ellagic acid22, catechin, propyl gallate, esculin) may help in the prevention of lung cancer due to tobacco smoke (Yang 2010, 2006; Kim 2008; Bryja 2003; Wang 2002; Chu 2001; Kawaii 2000, 2001; Hecht 1999; MartinAragon 1998; Matsunaga 1998, Miller 1996; Sharma 1994; Kitagawa & Noguchi 1994; Noguchi 1995, 1993; Teel & Castonguay 1992; Konoshima & Lee 1986). Recent investigations have an expanded scope which suggests anticancer potential for aescin in colon and liver cancer cells, cholangiocarcinoma cell lines, oral cancer, leukaemia and multiple myeloma (Park 2011; Shen 2011; Zhang 2011; Park 2010, 2008; Harikumar 2010; Tan 2010; Kok 2009; Zhou 2009; Lin 2009; Kaneko 2007, 2004, 2003; Patlolla 2006). The potential use of escin to potentiate drug treatment (gemcitabine) in pancreatic cancer studies has attracted recent interest as this condition is very resistant to treatment (Wang 2012). Other, equally interesting, aspects of the pharmacological properties of esculetin appear extremely useful from a clinical point of view. Esculetin has shown potentiating effects on the anticancer activity of 5-fluorouracil, taxol and cisplatin, as well as an ability to protect against renal toxicity and immunosuppression (Tikoo 2011; Ming 2010; Kuo 2006). This renoprotective effect may extend to benefits for diabetic individuals and HIV treatment protocols (Surse 2011; Grases 2004). Aescin has also shown experimental hypoglycaemic activity that may contribute to its value (Yoshikawa 1996, 1994). In addition, studies have suggested aescin, in combination with troxerutin (a flavonoid with vasoprotective properties23), has benefits for inner ear problems and associated hearing loss (Siegers 2008). 22 In some studies the antimutagenic and anticancer agent ellagic acid was shown to be more effective than esculetin or esculin in inhibiting lung tumours (Boukharta 1992). 23 Troxerutin (a rutin derivative) which has been isolated from the Japanese Pagoda Tree (Sophora japonica), has been marketed as an antithrombosis agent. Experimentally, this flavonoid has shown protective effects on brain function that may be useful for diabetics and some forms of memory disorder (Lu 2010). Clinical trials suggest that a combination with products such as pycnogenol or coumarin provide substantial benefits for venous insufficiency (Riccioni 2004; Vanscheidt 2002). One clinical study showed enhanced post-surgical recovery following haemorrhoid resection, when used in combination with the antihaemorrhagic agent carbazochrome (Basile 2001).


Esculetin: Traditional Herbal Resources

Fraxinus rhynchophylla bark. (Courtesy Dalgial, Wikimedia Commons, CC-by-SA 3.0 Unported)

Chinese studies of coumarins sourced from Fraxinus cortex (Fraxinus rhynchophylla24, Oleaceae family) have indicated that esculetin and esculin have beneficial effects on hyperuricaemia and renal dysfunction (Li 2011). The herb is traditionally utilised as an expectorant, antitussive, anti-asthmatic, antidiarrhoeal agent, as well as being considered useful for cataract and liver dysfunction (Yeung 1985). Recent studies have established hepatoprotective anti-fibrotic effects on liver cells that suggest its use for the treatment of viral hepatitis. The esculetin content of the extract was quite high (33.54 mg/g) – and its antifibrotic activity was superior to that of the Milk Thistle. The closely related Fraxinus excelsior has equally significant medicinal properties with studies indicting antioxidant, antirheumatic, anti-inflammatory, analgesic and antipyretic activity. The seeds are a potent hypoglycaemic and hypotensive agent (Tien 2011; Peng 2010). 24 Qin-pi (Chin-pi) from Fraxinus bark can also be sourced from Fraxinus bungeana – although there are other substitutes such as F. stylosa, F. chinensis or F.chinensis var. acuminata.

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The presence of aesculetin (or aescin/escin) in other herbal products may have similar benefits. Its liver-protective effects may well be important in the activity of various herbs traditionally utilised for treating liver disorders – such as Chicory (Cichorium intybus) and Bougainvillea spectabilis. Esculetin has also been identified as an antimutagenic agent in Alchemilla speciosa, while esculetin and scolymoside were the active antioxidant components of Artemisia montana (Kim 2000; Schimmer & Eschelbach 1997).

Artemisia capillaris. Esculetin, which has important antioxidant and anti-inflammatory properties, is present in a number of Artemisia species (e.g. A. capillaris, A. montana, A. scoparia) that have been traditionally utilised for treating skin inflammation and/or liver disorders (Kwon 2011; Pan 2003; Kim 2000). (Image courtesy Wayne Cheng, flickr)

Xanthine Oxidase: An Inflammatory Enzyme

‘The Gout’ by James Gillray, published 14 May 1799.

Gout is a form of acute inflammatory arthritis that most frequently affects the big toe – although the condition is not confined to this

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joint and more systemic manifestations can affect other joints (heel, knee, wrist, fingers) with the formation of trophi (uric crystal accumulations). This can, at times, affect the kidneys with the development of renal stones (urate nephropathy) also resulting from a reduced excretion of uric acid (hyperuricaemia). Gout sufferers can also experience fever and fatigue. The condition tends to be associated with dietary triggers such as alcohol, fructose sweeteners, meat and seafood, as well as various forms of trauma (including surgery) and some drug therapies (e.g. niacin, aspirin, immunosuppressant drugs and some diuretics). The use of vitamin C and coffee are among the dietary strategies that help to reduce the incidence of the condition.

Crystallographic structure (monomer) of xanthine oxidase from bovine milk. This is a complex compound, with the colours indicative of different components: bounded flavin molecules (FAD, in red), ferridoxin-iron sulfur clusters (Fe-S, in orange), molybdenum atoms (molydopterin cofactors, in yellow) and salicylate (blue). (Image courtesy Yikrazuul, Wikimedia Commons, CC-by-SA 3.0)

Gout is an inflammatory condition that involves the action of an enzyme, xanthine oxidase, which is involved in the production of uric acid crystals from xanthine and hypoxanthine. Gout is often (but not always) characterised by raised uric acid levels (hyperuricaemia). It is treated with painkillers, anti-inflammatory drugs

(NSAIDs), steroids, colchicine (which is specific for gout), and xanthine oxidase inhibitors such as the drug allopurinol. Xanthine oxidase is normally present in the liver and blood levels may be raised in cases of fairly severe liver damage. Additionally, xanthine oxidase may be involved in cardiovascular disorders and oxidative eye damage. Studies of natural products with potential for the treatment of gout have indicated that aesculin injections could reduce serum urate levels (salts of uric acid) in animals. Strangely enough, this hypouricaemic effect was not linked to xanthine oxidase activity – even though esculetin has shown inhibitory effect on this enzyme (Lin 2008; Kong 2002; Chang & Chiang 1995).

Berry fruits, and cherries in particular, have been shown to have excellent anti-gout and anti-arthritic properties (Kelly 2006; Jacob 2003). The effective dose appears to vary from 6 cherries (around 50 g) to 200 g, which effectively lowers uric acid levels and prevents gouty ‘flare-ups’ – an effect due to the anthocyanidin components that inhibit xanthine oxidase activity. Canned or frozen berries are equally as effective as the fresh fruit. Other berry fruits that appear to be useful include Hawthorn, Blueberry, Cranberry and possibly even Strawberry, although they have to be the dark, rich-coloured varieties.


A Renewed Interest in Native Flora

The clinical value of the Australian flora is quite evident from the preceding discussion, which has provided numerous illustrations of the practical value of traditional herbal medicines – and their continued role as therapeutic agents. In addition, there have been various efforts aiming toward a more extensive evaluation of native plant chemistry (phytochemistry). Some species have shown excellent practical value, leading to some unique Australian products reaching the marketplace. The antimicrobial and aromatic properties of Lemon Myrtle and Tea-tree oils are among the most successful of these. However, there are many other plants with innovative pharmaceutical potential about which we know very little – although what we do know can engage one’s curiosity.

A unique range of balms sourced from native Australian plants. (Courtesy Australian Native Therapies)

Backhousia citriodora is highly rated as an Australia aromatic medicinal herb with a broad spectrum of antibacterial activity. Its wonderful fragrant qualities make it an excellent candidate for use in diverse cosmetics and skin-cleansing products – and for treating unsightly skin problems such as acne and blemishes, as well as numerous forms of skin irritation (including psoriasis), fungal problems (e.g. tinea) and some viral infections (notably molluscum contagiosum) (see Volume 1 for further details). (Image courtesy Lemon Myrtle Essentials)

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Phytochemical evaluations of the flora have resulted

in a number of discoveries with intriguing medicinal potential. Antiviral agents such castanospermine (and derivatives) from the Blackbean (Castanospermum australe) and prostratin25 from the Milky Mangrove (Excoecaria agallocha) have been seriously investigated for use in the treatment of HIV. Many species of the endemic genus Eremophila contain unqiue diterpenes with antimicrobial properties, which include an activity against drug-resistent strains of bacteria. There are also recent innovative developments with regard to the use of Bastard Sandalwood oil (Eremophila mitchellii) as a termiticide (see Chapter 7). There are some instances where Australian initiatives have extended beyond the endemic flora. Indeed, numerous Euphorbia species (both native and naturalised) have equally interesting antibacterial potential. The latex of a few species also acquired a reputation as an effective skin cancer treatment – a folk remedy that appears to have excellent clinical potential. In particular the Radium Weed or Milkweed (Euphorbia peplus), which was introduced into Australia in the early 1800s, provided a well-known local remedy for warts, corns, waxy growths, sun cancer and rodent ulcers. Joseph Maiden commented: ‘it is stated that the natives of the Northern Territory use the juice of a species of Euphorbia as a specific in smallpox. Another species affords a juice said to be a remedy in cancer. Without committing oneself to an expression of opinion as to the utility of the Euphorbias alluded to, our native species will doubtless well repay a thorough examination of their medical properties’ (Maiden 1889). More than a century later, investigations of Radium Weed by an Australian company, Peplin Biotech Pty Ltd, have produced a cream formulation for clinical use. In 2001, the Executive Summary of a Rural Industries Research and Development Corporation (RIRDC) report on the plant’s medicinal potential by Davis and Parsons commented: ‘An early clinical trial on thick and thin non-melanoma skin cancers has confirmed that the compounds are very effective in producing long-term (possibly permanent) responses in human patients without any evident systemic toxicity when applied topically. This 25 Prostratin was originally isolated from the New Zealand plant Pimelea prostrata. It is also present in the Samoan tree Homalanthus nutans and some medicinal Euphorbia, notably the Chinese herb E. fischeriana (Tang 2012).

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is highly significant because current topical methods of drug treatment require long periods of application without being fully effective, and physical methods (e.g. surgery) are expensive and difficult to apply to the large areas affected, especially in older people.’ High praise indeed.

In a review of 39 native plants (from which 56 extracts were prepared), Euphorbia australis (whole plant) was the only species active against both gram-negative and grampositive bacteria (Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhimurium) – albeit the inhibitory action was incomplete. Numerous Euphorbia species have long been utilised as antibacterial and healing agents. In Australia, E. australis has been employed as a medicinal wash for skin sores – as was E. drummondii (pictured here), which was also considered useful for genital sores, fevers, and as an antidysentery remedy (Palombo & Semple 2001). (Image courtesy Howard Rawson, flickr)

Euphorbia peplus. (Courtesy Kim & Forest Starr, Hawaii)

Euphorbia hirta, which is widely naturalised throughout the continent, is also considered to have anticancer and antiviral (anti-HIV) properties worthy of commercial development (Davis & Parsons 2002).

Table 3.2 Overview of Australian Plants Examined for Biological Properties in Recent Scientific Literature that are of Interest for Medicinal Purposes Notes: 1. See Volume 1 for Santalum and Syzygium. 2. See Volume 2 for Acacia, Eucalyptus, Leptospermum and Melaleuca. Essential oils are not included here as they are 3. discussed in detail under individual plant species in each volume. 4. There is a comprehensive review focusing on the CSIRO phytochemical studies that provides details of alkaloidal substances in the native flora, as well as anti-tumour studies. This has been published in Plants for Medicines by DJ Collins and colleagues (1990). 5. A review of tropical rainforest plants from Northern Queensland lists 23 extracts with antimicrobial activity and 27 extracts with cytotoxic activity. Only the main results are included in this table (Setzer 2001).


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Table 3.2 Overview of Australian Plants Examined for Biological Properties in Recent Scientific Literature that are of Interest for Medicinal Purposes Species Acacia aulacocarpa Acacia complanta Adansonia gregorii Ajuga australis Allocasuarina littoralis Araucaria bidwillii (see also Volume 2) Asteromyrtus symphyocarpa Asteromyrtus shepherdii Amyema quandong

Astrotricha longifolia

Traditional medicinal use (if any) Investigations (reference) Leaf: antibacterial, more active against gram-positive bacteria (Cock 2012b). Leaf: antifungal against Aspergillus niger (Cock 2012b). Flower: limited activity; antibacterial against Bacillus subtilis (Cock 2012b). Flowers: antimicrobial (Cock 2008a). Extracts: acaricidal activity; extracts and ajugarin I showed strong insect antifeedant activity against Plutella xylostella (Rasikari 2007). Leaves: broad-spectrum antibacterial, particularly good activity against gram-positive bacteria (Cock 2008a, 2008b, 2008c). Bunya Nut extracts: good broad spectrum of antibacterial activity (Vesoul & Cock 2012). Use: headache, aches and pains. Leaves: anti-migraine potential (Rogers 2000). Bark: antiviral (anti-HSV) activity (Setzer 2001). Use: Feverish conditions. Leaves: antibacterial, active against drug-resistant bacteria (Palombo & Semple 2002; Palombo 2001). Leaves: antimicrobial (Cock 2008a). Leaves: antimicrobial (Cock 2008a).

Backhousia citriodora (see also Volume 1) Banksia collina

Leaves: antimicrobial (Cock 2008a).

Balanops australiana

Bark: antiviral (anti-HSV) activity (Setzer 2001).

Beyeria lechenaultii Boronia spp.

Use: general sickness and fevers. Aerial parts: antibacterial (Palombo 2001). Alkaloids and flavonoids from four species: antibacterial activity (Nazrul Islam 2002).

Brachychiton acerifolius

Flowers: antimicrobial (Cock 2008a).

Buckinghamia celsissima Callistemon citrinus

Leaves: significant bread-spectrum antibacterial activity; antifungal against Candida albicans and anti-yeast against Saccharomyces cervisiae (Cock 2009a, 2008a). Leaves and flowers: antimicrobial (Cock 2008a).

Callistemon salignus

Leaves and flowers: antimicrobial (Cock 2008a).

Casearia grayi

Stem: antimicrobial, antioxidant. Leaf: antioxidant, cytotoxic (Mosaddik 2004). Root: antimicrobial. Leaf: antioxidant. Stem: cytotoxic (Mosaddik 2004). Leaf: high antioxidant activity (Mosaddik 2004).

Casearia multinervosa

Casearia sp. (Mission Beach) Carissa lanceolata Castanospermum australe Centipeda cunninghamii

Ceratanthus longicornis

Use: chest pain, toothache, colds, flu, rheumatic pain; insect repellent. Root: antibacterial activity (Hettiarachchi 2009). Use: toxic properties, seeds processed and used as food. Seeds: anti-HIV activity; isolation of castanospermine (Roja & Heble 1995). Use: coughs, colds, skin infections. Extracts: anti-inflammatory, antioxidant; skin-healing, rehydrating and cellular protective activity (see page XX). Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Clematis pickeringii

Stem: anti-inflammatory (Li 2005, 2003).

Clerodendrum floribundum

Use: aches and pains, headache, skin complaints, infected or inflamed eyes, diarrhoea, bronchial congestion. Xanthine oxidase inhibitory activity (Sweeney 2001).

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Clerodendron traceyi

Leaf and stem: acaricidal activity (Rasikari 2005).

Conospermum incurvum Conospermum brachyphyllum Cryptocarya corrugata

Conocurvone, antiviral (anti-HIV) activity (Cannon 1999; Dai 1994).

Cymbopogon ambiguus

Dianella callicarpa

Use: respiratory tract infections, headache, fever, skin disorders, eye wash. Leaf: weak antiviral against Ross River virus (Semple 1998). Whole plant: anti-migraine potential (Rogers 2001). Root: significant antimicrobial and antiviral activity (Dias 2009b).

Dianella longifolia var. grandis

Roots: antiviral against poliovirus (Semple 2001, 1998).

Dianella revoluta var. revoluta Doryphora sassafras (see also Volume 1) Drypetes lasiogyna

Use: colds, general sickness. Roots: weak antiviral against human cytomegalovirus (Semple 1998). Use: highly aromatic; tonic. Alkaloid-rich bark: alkaloid with antimalarial activity isolated (Buchanan 2009). Bark: antiviral (anti-HSV) activity (Setzer 2001).

Eremophila

Numerous species have antimicrobial properties (for details of chemistry see Chapter 7).

Erythrina vespertilio

Glossocarya calcicola

Use: headache, sore eyes; sedative. Bark: anti-migraine potential (Rogers 2001). Use: skin sores, medicinal wash; cancers, stimulate milk flow (lactagogue) Whole plant: antibacterial (Palombo 2001) Whole plant: antiviral against human cytomegalovirus (Semple 1998) Use: skin sores, genital sores, fever, rheumatism, warts, anti-diarrhoeal (dysentery, chronic diarrhoea). Whole plant: weak antiviral against human cytomegalovirus (Semple 1998). Use: mashed bark infusion rubbed over skin to ease pain, or for ‘sickness’ (Roth 1903); sap or leaf decoction widely used to treat ulcers. Twigs and bark: contain prostratin, which has antiviral (anti-HIV) potential. Use: inflammatory disorders, mumps, smallpox, gonorrhoea, bleeding disorders (haematuria, haemoptysis, menorrhagia). Bark: anti-inflammatory (Li 2003). Leaf extract: strong cytotoxic activity; clerodane triterpenes isolated (Rasikari 2007).

Grevillea juncifolia


Grevillea pteridifolia

Grevillea striata

Endophyte (NRRL 30566): This strain of Streptomyces produces novel antibiotics (kakadumycins). Kakadumycin A has broad spectrum of antibiotic activity, especially against gram-positive bacteria, and impressive activity against malaria parasite (Plasmodium falciparum) (Castillo 2003). Leaves and flowers: antimicrobial (Cock 2008a). Phenolic compounds isolated with potential cardiovascular activity (Roufogalis 1999). Phenolic compounds isolated with potential cardiovascular activity (Roufogalis 1999).

Haemodorum simplex

Bulb and aerial parts: antibacterial, antifungal, antiviral studies (Dias 2009a).

Ipomoea pes-caprae subsp. brasiliensis Isotoma petraea

Use: headache, aches and pains, marine stings. Whole plant: anti-migraine potential (Rogers 2000). Use: Respiratory disorders. Whole plant: weak antiviral against Ross River virus (Semple 1998). Leaves: antimicrobial (Cock 2008a).

Euphorbia australis

Euphorbia drummondii

Excoecaria agallocha

Ficus racemosa

Grevillea robusta

Jacksonia scoparia Kennedia nigricans (misspelt K. nigriscans in the original research paper) Lepidosperma viscidum

Leptospermum petersonii (see also Volume 2)


Leaf endophyte (Streptomyces) with antibacterial, anti-mycobacterial and anti-malarial (anti-plasmodial) activity; antibacterial compounds (munumbicins) identified (Castillo 2006, 2002). Use: colds. Stem base: antibacterial; active against drug-resistant MRSA (Tomlinson & Palombo 2005; Palombo & Semple 2002; Palombo 2001). Essential oil: antifungal against dermatophytes (Park 2007).


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Macadamia integrifolia

Flowers: antimicrobial (Cock 2008a).

Mirbelia oxylobiodes


Morinda citrifolia Neolitsea dealbata

Use: wounds, ulcers, antiseptic. Fruit powder: anti-inflammatory (Li 2003). Bark: antiviral (anti-HSV) activity (Setzer 2001).

Pittosporum hirtellus

Extracts: in vitro antiviral activity, but was not active in vivo (Shead 1992).

Pittosporum phylliraeoides var. microcarpa (see also Volume 1)

Plectranthus habrophyllus

Use: colds, coughs, skin complaints; also as anticancer agent. Fruit, wood, leaves: antiviral against Ross River virus (Semple 1998). Dried plant material: broad spectrum of antibacterial activity; antifungal against nystatin-resistant Aspergillus niger (Cock 2011). Leaf extracts: experimental tumour cell inhibition; cytotoxic and immun stimulation (Lindquist 2007). Use: antiseptic; wounds, ulcers, sores; itching skin disorders (prickly heat), chicken pox. Leaves: anti-mycobacterial activity (McRae 2008). Acaricidal activity against mites (Tetranychus urticae). Other species had acaricidal potential including P. graveolens (Rasikari 2007). Leaf and stem: acaricidal activity (Rasikari 2005).

Plectranthus sp. (Hann Tableland)

Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Podocarpus grayae


Premna serratifolia

Leaf and stem: acaricidal activity; low cytotoxicity (Rasikari 2005).

Prostanthera rotundifolia

Aromatic fragrant herb. Essential oil: antifungal activity against Botrytis cinerea, a grape pathogen of vineyards (Antonov 1997). Use: colds, respiratory infections, skin sores, eye complaints. Aerial parts: antiviral against poliovirus, flavonoid active against picornaviruses (Semple 1999, 1998). Aerial parts: anti-mycobacterial (Meilak & Palombo 2008). Use; colds, flu, sore throat, venereal disease, dysuria. Leaves: antibacterial (Palombo 2001).

Planchonia careya Plectranthus diversus

Pterocaulon sphacelatum

Santalum lanceolatum (see Volume 1 for a review of Australian Santalaceae) Scaveola spinescens Scolopia braunii Stemodia grossa Syzygium australe (see also Volume 2) Syzygium luehmannii Tasmannia lanceolata

Terminalia ferdinandiana (see also Volumes 1 & 2) Tinospora smilacina Xylosma terrae-reginae

Use: boils, skin sores, gastrointestinal disorders, urinary problems. Stems and leaves: antiviral against human cytomegalovirus (Semple 1998). Stem: antimicrobial, antioxidant. Leaf: antioxidant, cytotoxic (Mosaddik 2004). Use: colds, rheumatism, headache. Xanthine oxidase inhibitory activity (Sweeney 2001). Leaves: good broad-spectrum antimicrobial activity; also antifungal activity against Aspergillus niger (nystatin-resistant strain) (Cock 2012, 2008a). Leaves: minor antibacterial activity (Cock 2012). Use: flavouring, spice. Pepperberry extracts and polygodial have shown antioxidant and gastroprotective properties (Netzel 2006; Matsuda 2002); polygodial has substantial antibacterial and anti-candida activity, as well as anti-inflammatory, analgesic, cytotoxic and anti-allergic properties (Kubo 2005, 2001; da Cunha 2001). Fruit: strong antioxidant activity; high levels of vitamin C, phenolics (including gallic and ellagic acids) and anthocyanins (Mohanty & Cock 2012). Fruit pulp extracts: good broad-spectrum antibacterial activity (Cock & Mohanty 2011). Use: catarrh, colds, cough, diarrhoea, swelling, trachoma, ophthalmia. Stem: anti-inflammatory (Li 2003). Root: antimicrobial, cytotoxic. Stem: antioxidant Leaf: cytotoxic (Mosaddik 2004).

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Eucalypt woodland and freshwater stream. (Courtesy Craig Nieminski, flickr)

 The antimicrobial properties of the Australian Eucalypts are diverse and continue to be a subject of interest. (Volume 2 provides a substantial review of the subject.) Recent studies on Eucalyptus major (leaf, flower) and E. baileyana (leaf ) have shown excellent antibacterial potential, particularly against gram-positive bacteria – although they were devoid of antifungal properties. These studies of are of interest as they utilise methanolic plant extracts, rather than an essential oil. The latter is difficult to evaluate due to the insolubility of the oil in bacterial agar-gel studies and often a solubilising agent is utilised, which can give variable results. Methanolic extracts overcome this technical difficulty (Cock 2009b, 2008a). Table 3.2 highlights the fact that Australian scientists are continuing to significantly expand their knowledge regarding the medicinal flora of this continent – an effort that is not widely acknowledged.

While we occasionally we hear of some new ‘breakthough’, most of us would little appreciate the decades of research that have usually accompanied such developments. Many reports have been filed away in scientific journals, and it can difficult to link chemical reports with practical clinical developments. The search has been further hampered by the fact that, until relatively recently, there has been little incentive for Australian companies to engage in expensive research efforts. This has slowly changed, although there are still quite serious problems with a burdensome bureaucracy that can be counterproductive and, in some cases, outright obstructive. Past initiatives in Australia have been compromised by a lack of governmental support, and there have been profitable enterprises such as the Duboisia alkaloids (see Chapter 9), that were taken over and developed by overseas concerns – while other ventures have faded into obscurity. It would be a great pity if this trend were to continue.

Chapter 4

NEW ROLES FOR OLD REMEDIES Australian native herbs have impressive healing attributes – although only a few have been exploited to their full potential. However, there are other traditions that indicate profound medicinal potential for some of these plants, or their close relatives, that have hitherto been largely ignored in this country. In many cases, the traditional use of numerous herbs has been verified by modern investigation, which serves to enhance their practical value. Some studies hint at greater healing attributes than is immediately apparent – as pharmacological evaluations of the Horsechestnut, Gotu Kola and Brahmi illustrate. Their benefits range from venous, tonic and woundhealing activity, to liver and kidney protective properties, as well as significant effects for memory enhancement. Gotu Kola is one of the herbal remedies with particularly interesting antimicrobial attributes that once led to its extensive use as an antileprotic remedy – a disease that many of us mistakenly consider a remnant problem, relegated to historical significance. The reality of the situation is quite different. The story of leprosy, an intractable disease with disastrous consequences for the sufferer, involves a rather amazing search for wound-healing remedies and a complex tale of antibiotic discovery. Even so, the role for herbal medicines, somewhat surprisingly, remains as valid today as in the past.

Gotu Kola.

and rockeries. It flourishes particularly well on damp swampy sites. The plant, which has also been known as Miner’s Lettuce, favours the east Australian coast, ranging from Victoria to tropical Queensland – as well as a being found in a few places in South Australia and southwest Western Australia. Despite its impressive medicinal potential, Centella asiatica is often considered to be little more than a tropical weed. The botanical literature, with regard to the classification of Centella and Hydrocotyle, can be somewhat confusing. Some authorities regard Hydrocotyle asiatica and H. cordifolia as synonyms for Centella asiatica – although others regard them as separate species. These plants are virtually indistinguishable in appearance. In addition, Gotu Kola has sometimes been erroneously known as Brahmi – a term ascribed to Bacopa monniera. It is a pity that many small herbs such

Centella: Ancient Remedy for the Modern World A Coastal Weed Gotu Kola or Indian Pennywort (Centella asiatica, formerly Hydrocotyle asiatica) is a slender creeping plant of garden edges, shady stone walls 137

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An early report in the Agricultural Gazette of New South Wales made mention of an indigenous plant possessing medicinal properties (Maiden 1894):

Gotu Kola as herbal lawn cover, no mowing required.

as Hydrocotyle and Centella are often seen as nuisance weeds. Surely some daisies, dandelions, oxalis, clovers and pennyworts could add an attractive diversity to the lawn environment, with the added benefit of a low growth habit and colourful flowers – although invasive imported weeds such as the Singapore Daisy (particularly in the rainforest environment) would be an exception. Certainly native species that can be utilised as natural lawn alternatives may be best left alone – rather than using expensive herbicides that poison the soil and add to chemical run-off in the urban setting. Gotu Kola or Indian Pennywort (Centella asiatica) is native to India, China, Indonesia, Australia, the South Pacific Islands, Madagascar and southern/central Africa. Throughout its range it has been regarded as a wound-healing herb par excellence. The fresh plant (or its juice) has been utilised in the treatment of a great diversity of wounds that range from abscesses and ulceration (chronic, scrofulous, or syphilitic with gummatous infiltration) to innumerable skin problems (psoriasis, chronic or obstinate eczema, boils, furunculosis, sweat rash). The entry for Centella asiatica in the 1868 Pharmacopoeia of India states: ‘In anaesthetic leprosy good results have followed the use of this herb, but it possesses no claim to the character of a specific attributed to it by some. It has been found more useful in secondary or constitutional syphilis, especially in those cases where the skin and subjacent cellular tissue are principally affected. In non-specific ulcerations, and in skin diseases, it is of value, both as an internal and as a local remedy.’

[Hydrocotyle] asiatica is found in moist places in many parts of the Colony. In the coast districts, and particularly near the northern rivers and table-lands where there is rich soil, it grows in the greatest profusion, covering the ground for large areas with a carpet of bright green … Mr. G. M. M’Keown, Manager of the Experimental Farm at Woollongbar, Richmond River, recently sent this plant to the Department, stating that it is ‘credited locally as valuable when applied to wounds or sores in the form of a salve or poultice’. This is the first occasion on which I have heard of it being put to use in New South Wales, but it is a well-known remedy in India, having been in use amongst the natives for many centuries.

Brisbane doctors accorded it similar esteem and the herb even gained some official recognition. In 1888 Gotu Kola was an exhibit at the Melbourne Centennial International Exhibition. The report in the Agricultural Gazette continued: The Pharmacographica Indica (1891) confirms the above estimate of the therapeutic value of the drug, and also states that it is so abundant in the Mauritius [Islands] that it serves as forage for cattle, whose milk it improves; it is also greedily eaten by pigs and other domestic animals. It is the more desirable to draw attention to an indigenous medicinal plant, as we have so few that, in the present state of our knowledge, possess undoubtedly valuable properties. In the bush it will be most convenient to employ the plant in the manner and for the uses indicated in Mr. M’Keown’s note.

The Pennyworts Centella (Apiaceae) was formerly placed in the genus Hydrocotyle – which belongs to a different family classification, the Araliaceae. Over half the Hydrocotyle genus is found in Australia (41 of a total of 75). These fairly attractive creeping herbs of marshy and boggy places are often known as Pennyworts, and have a somewhat similar appearance to Gotu Kola. The Large-leaf Pennywort (Hydrocotyle bonariensis) is of interest as it is a medicinal herb that is widely distributed across the globe – from tropical and South Africa to the southern United

NEW ROLES FOR OLD REMEDIES

Hydrocotyle bonariensis. (Upper image courtesy Donald Hobern, flickr; lower image courtesy Franz Xaver, Wikimedia Commons, CC-by-SA 3.0 Unported)

States, Central and South America. In Australia it is found along the coastline from southern Queensland to Victoria, South Australia and Western Australia (southwest region). The plant has been utilised for treating inflammatory skin disorders including psoriasis, and as a cosmetic for freckles and skin spots. Extracts possess antifungal (fungicidal) activity against Candida krusei. This herb has also shown significant antiparasitic activity against Leishmania amazonensis (Tempone 2008).

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The Whorled Pennywort (Hydrocotyle verticillata) is a native species found throughout southeastern Australia, ranging to inland Queensland and South Australia, as well as southwest Western Australia – although it does not extend to the northern tropics or Tasmania. This species is often utilised as an aquarium foliage plant. (Image courtesy Kim and Forest Starr, Hawaii)

The Lawn Marsh Pennywort (Hydrocotyle sibthorpioides) is prolific throughout Victoria and Tasmania, extending along the coastline of New South Wales into southern Queensland. This native species has shown substantial immune modulatory and anticancer potential. The aquarium herb known as Brazilian Pennywort (Hydrocotyle leucocephala) is also of interest due to its immunosuppressive components (Huang 2008; Yu 2007; Ramos 2006). (Image courtesy Kim & Forest Starr, Hawaii)

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A Remarkable Therapeutic Repertoire Investigations of Centella asiatica and its components confirm significant wound-healing attributes. The Gotu Kola herb can directly promote collagen synthesis, which is important because collagen is a major skin component that is directly involved in the healing process. The effects are linked to its triterpene components – the most prominent of which are asiaticoside and madecassoside, and their sapogenins (asiatic acid and madecassic acid). In the past, particular emphasis has been placed on the cellular healing and antimicrobial effects of asiaticoside, although madecassoside appears to have equally impressive activity (Paolino 2012; Somboonwong 2012; Belcaro 2011; Hashim 2011; Maquart 1999; Sunilkumar 1998; Suguna 1996; Bonte 1995, 1994, Rush 1993). The effects of asiaticoside are multifaceted. It has substantial antioxidant and anti-inflammatory properties which facilitate the initial stages of healing.1 It can increase the vascularisation of connective tissue, provide support for the tensile integrity of the skin, and facilitate keratinisation (keratin is a protein primarily found in skin, nails, hair, tooth enamel), which is involved in skin formation – thereby also having a stimulant effect on hair and nail growth (Turton 1993; Shukla 1999a, 1999b). Importantly, not only does Gotu Kola promote skin repair, it also strengthens the cellular structure of the skin, maintaining its integrity. The use of the herb in the treatment of venous insufficiency, inflammation (phlebitis) and for ulceration of the extremities (e.g. leg ulcers) is not only based on a wound-healing effect – there is a supportive action on the venous circulation, with substantial antiinflammatory benefits. Bed sores and diabetic ulcers, which likewise involve impaired circulatory function, respond well to treatment with Gotu Kola. It can promote the formation of new epithelial cells and connective tissue, allowing the damaged tissue to be discarded more quickly. Therefore, burns heal quicker with its use, and it can reduce keloid (scar) formation (Somboonwong 2012; Kimura 2008; Liu 2008b; Altern Med Rev 2007). 1 The antioxidant activity of Centella asiatica (84%) has been found comparable to that of grape seed extract (83%) and vitamin C (88%) (Hashim 2011).

Gotu Kola extracts have anti-inflammatory, anti-pruritic (anti-itching) and anti-allergic properties (George 2009). Serious investigation of its use as a topical treatment for psoriasis has been suggested (Sampson 2001). The anti-inflammatory and antioxidant triterpenes asiaticoside and madecassoside make a significant contribution to its anti-psoriatic properties. Gotu Kola also has potential for use in cellulitis – a diffuse inflammatory disorder characterised by localised hot red patches of skin irritation (e.g. erysipelas) that can become extensive. The condition can be extremely painful and debilitating (Morganti 1999; Kartnig 1988). In addition, experiments tend to confirm an immunesupportive effect (Punturee 2005a, 2005b, 2004; Jayathirtha & Mishra 2004). The use of Centella in individuals with compromised immune system function, particularly where circulatory impairment can delay wound healing (such as diabetes), is certainly justified. A number of studies indicate Gotu Kola extracts can be useful following surgery. The herb has the ability to promote mucous membrane healing in ear, nose and throat surgery – for example, following tonsillectomy. It can enhance the healing process for all manner of surgical wounds (including episiotomy lacerations following childbirth) – as well as radiation-induced ulceration (Mowrey 1990). A cream combining Centella asiatica and Bulbine frutescens has been used clinically as a supportive healing agent following plastic surgery, specifically for the reduction of scar tissue formation. The cream not only promoted collagen production and facilitated wound healing, it had useful antibacterial and antiinflammatory activity (Widgerow 2000). Many products on the market that contain Gotu Kola are equally effective. Cream formulations combining Gotu Kola with ɑ-tocopherol and collagen-elastin hydrolysates can prevent the stretch marks of pregnancy – a combination that was found to be particularly useful for women who had developed them previously (Young & Jewell 2000). Gotu Kola may help prevent skin ageing and wrinkles. The herb has photoprotective properties and a cream prepared with madecassoside and vitamin C showed substantial benefits for chronic sun-damaged (photoaged) skin (Saraf 2012; Haftek 2008). Research continues to improve the bioavailability of Centella formulations


A South African herb known as the Burn Jelly Plant (Bulbine frutescens) is well named. The fresh leaf yields a soothing mucilaginous juice with an excellent healing reputation that is particularly useful for burns – as well as all sorts of skin irritation (rashes, blisters, insect bites), cracked or fissured skin problems (lips, feet), acne, mouth ulcers and even cold sores (www.plantzafrica.com). (Image courtesy Stan Shebs, Wikimedia Commons, CC-by-SA 3.0 Unported)

Calendula officinalis. (Courtesy Fanghong, Wikimedia Commons Project, CC-by-SA 3.0 Unported)

on Calendula officinalis – instead it utilised a tincture of Marigold flowers from Tagetes patula with 10 per cent white paraffin. The results were very good: ‘After 3–4 weeks, patients using calendula ointment showed 30–40% reduction in depth and diameter of the trophic ulcers and absence of any secondary infection, despite their refusal to immobilize the affected part.2 Since calendula is a natural product with no known untoward effects we feel that our observations may be useful to field personnel facing similar problems’ (Kartikeyan 1990). Calendula officinalis does have a similar effective reputation (Jorge-Neto 1996).

Circulatory and Cardiovascular Support

Tagetes patula. (Courtesy Michael Lahanas, Scientific-web. com)

for more effective clinical use, including the development of titrated extracts of Centella asiatica (TECA), organogels and hydrogels (Belcaro 2011; Morales 2009; Hong 2005; Kim 2001). A number of other remedies with good woundhealing and antibacterial attributes have equally interesting potential. For instance, ‘Calendula ointment’ has shown practical benefits for treating trophic ulcers such as those of leprosy. However, Kartikeyan and colleagues (1990) provide an illustration where checking the botanical identification is essential. Despite the name, the preparation used in the investigation was not based

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Gotu Kola has an excellent reputation for diverse conditions involving impairment of the venous system, such as haemorrhoids and varicose veins (MacKay 2001). In the last decade, investigations have greatly expanded its therapeutic scope. The benefits of the herb have long been known to traditional Indian and Chinese medical practitioners, although European interest lagged behind until the advent of studies undertaken in Italy in the 1990s (Cesarone 1994, 1992). Subsequently, greater recognition of the significant benefits of the herb by the medical profession resulted from clinical studies undertaken at St Mary’s Hospital, Imperial College, London (Cesarone 2001a, 2001b, 2001e; De Sanctis 2001; Incandela 2001b, 2001c). 2 Immobilising the affected site was part of the treatment protocol as this helps to promote healing and prevent repeated trauma. Plaster casts, however, were considered stigmatising and not very practical as most patients needed to continue working. Antibiotics (neomycin) were the common method of ulcer treatment (Kartikeyan 1990).

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Gotu Kola Tincture. (Courtesy Nutrition Care)

Studies on the use of a triterpene fraction for treating chronic venous insufficiency demonstrated a favourable influence on the circulatory status of diabetic individuals – as well as being useful for the treatment of venous hypertension. Although the initial clinical studies were small, the results were impressive. Importantly, the extract helped to prevent the deterioration of peripheral circulation that can be a seriously debilitating long-term consequence of diabetes. The herb also has potential for improving cardiovascular function, notably for the treatment of atherosclerosis. It can stabilise plaque formation and thereby reduce the risk of thrombosis. The fact that the extract can be used in conjunction with other drug therapies, and is very well tolerated, is a substantial therapeutic bonus (Cesarone 2001d; Incandela 2001a, 2001d). The use of Gotu Kola for the prevention of thrombosis on long-distance travel is another point of interest. Clinically, use of a triterpene-rich extract showed a marked reduction in ankle swelling and oedema. There were practical benefits for individuals undertaking long-haul flights or road travel that could be particularly useful for preventing microcirculatory problems. Importantly, the extract was effective even when used on a short-term basis. The dose was fairly low – 60 mg three times daily for two days before, as well as during the flight, with its use being continued for the following day (Cesarone 2001c). Of course, for seriously compromised circulatory problems a more long-term strategy would be appropriate. However, a word of caution is required regarding the use of herbal therapies that influence the circulatory system. Although they can provide substantial benefits, their use with blood-thinning

drugs such as warfarin (the use of which can be a complicated undertaking at the best of times) requires careful monitoring. Even so, this does not preclude the use of supportive herbal therapies. Centella’s therapeutic potential appears to be best evaluated according to its chemical characteristics, with an emphasis on asiaticoside and madecassoside as the compounds of primary interest. This has been made somewhat easier with the development of a number of standardised triterpenoid-rich extracts (James & Dubery 2009): • TECA (titrated extract): composed of asiatic acid (30%), madecassic acid (30%), asiaticosides3 (40%) • TTF (total triterpenoid fraction): composed of asiatic acid and madecassic acid (60%), asiaticosides (40%). • Madecassol extract: asiaticoside (40%), asiatic acid (29–30%), madasiatic acid (1%). There is another aspect of Gotu Kola’s chemical complexity that is worthy of note. The main components of the terpenoid-rich essential oil are: ɑ-humulene, β-caryophyllene, bicyclogermacrene, germacrene, myrcene, trans-β-farnesene, and p-cymol4 (James & Dubery 2009). Certainly, some of these would exert an influence on the activity of the herb. In addition, various other components are present in plant extracts: an alkaloid (hydrocotylin), flavonoids (kaempferol, quercetin, rutin) and other phenolic compounds (catechin), sterols (stigmasterol, sitosterol), amino acids, resin and a bitter principle (vellarine). The herb’s use as a vegetable is certainly supported by its nutritional value: vitamins (vitamins B, C, carotenoids) and minerals (calcium, magnesium, phosphate, sulphate, sodium, potassium, chloride). Indeed, iron levels can be quite high (12 mg/100 g). There is also a reasonable calcium (176 mg/100 g) and carotene (2400 mcg/100 g) content (Jamil 2007). The carotenoids of interest include β-carotene (255 μg/g dry weight), lutein (980 μg), neoxanthin (103 μg) and violaxanthin 9255 μg) (Chandrika 2010).

3 There is more than one form of asiaticoside. In addition to the original compound, asiaticosides B, C, D, E and F have been identified. 4 Other studies have shown variations in the main components. A volatile oil with antidepressant activity contained farnesol, elemene and caryophyllene. Another analysis showed ɑ-humulene, β-caryophyllene and bicyclogermacrene predominated (Zheng & Qin 2007).


A Complex Triterpenoid Chemistry Centella asiatica.

There appears to be quite a deal of variability in the constituents of Gotu Kola plants obtained from different sources. The herb can contain a number of components that are very similar chemically. However, the older literature is confusing, with duplicate chemical names, synonyms and, at times, contradictory findings marring the clarity of the picture (James & Dubery 2009). For instance, one study stated brahmic acid was identical with madecassic acid, while isobrahmic acid was a mixture of asiatic and madecassic acids (Kartnig 1988). Yet another report stated isobrahmic acid was identical to madecassic acid (an isomer of terminolic acid). Currently brahmic acid and madecassic acid are considered to be the same (6-β-hydroxy-asiatic acid) (James & Dubery 2009). For a long time Madagascar-sourced Centella asiatica was justifiably considered preferable as a wound-healing remedy due to its higher asiaticoside content. This was a fairly safe option, particularly as diverse studies reported considerable variability in plant extracts from other sources – a chemical complexity that would be, for most of us, quite bewildering. There are, however, varieties that maintain a great deal of similarity and the discovery of different chemical races of the herb has helped to clarify the situation (Kartnig 1988). The total triterpenoid content was, in general, found to be comparable between plants from India, Korea and Madagascar – although

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differences occurred in the ratio of free acids (e.g. asiatic acid) to glycosides (e.g. asiaticoside). Rosmarinic, betulinic and ursolic acids are additional compounds of pharmacological interest. Some species also contain saponins (e.g. centellasaponins A, B, C, D). The standard reference is: asiaticoside (1 mg/ ml), madecassoside (3 mg/ml) and asiatic acid (10 mg/ml) (Zainol 2008). Overall the following characterises plants obtained from different locations (James & Dubery 20095): • Madagascar: asiaticoside, asiatic acid, madecassoside and madecassic acid. Asiaticoside is present at high levels (2.6– 6.42% dry weight) in the leaf. The roots contain negligible levels. Cultivated plants had a much lower saponin content (asiaticoside 0.7–0.9%, madecassoside 1.1–1.6% dry weight). • South Africa: asiaticoside, asiatic acid, madecassoside and madecassic acid. • Sri Lanka: centelloside, centellic acid (plus centic and centoic acids). • Indian-sourced plants showed the greatest chemical variability (with different chemical types as listed): asiaticoside, asiatic acid, madecassoside and madecassic acid (plus brahmic acid) asiaticoside and asiatic acid  brahmoside and brahmic acid (plus isobrahmic acid)  brahminoside, brahmic acid (plus betulinic acid) thankuniside, thankunic acid (plus asiatic acid) isothakuniside and isothankunic acid (plus asiatic acid) • Malaysian samples (mg/ml) were found to be low in asiatic and madecassic acids (0.55 ± 4.58 mg; 0.55 ± 0.89 mg, respectively), although the level of madecassoside (3.1 ± 4.58 mg) and asiaticoside (1.97 ± 2.65mg) were good (Hashim 2011). 5 A complete list of triterpenes and their chemical structures is available in James & Dubery (2009). Ursolic and betulinic acids are discussed in greater detail in Volume 2 under Triterpene discoveries.

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• Southern Malaysian samples (mg/ml): asiaticoside (2.5 mg), madecassoside (5.3 mg), asiatic acid (3.4 mg) (Zainol 2003). Other leaf samples6 have shown substantial variability (mcg/ml): asiaticoside (0.39– 2.56 mcg), madecassoside (0.71–5.3 mcg), asiatic acid (undetectable–1142.67 mcg). Substantial levels of asiatic acid (2390 mcg) were also present in the petioles. • Australian sources have similar potential for chemical variability. It is also possible that the native herb is not entirely botanically identical with overseas samples and may even be a different variety or sub-variety. At one time the native plant was assigned a separate species name, Centella cordifolia. 6 While root samples normally contain minimal amounts (if any) of these triterpenes, in this study levels of 3421 mcg/ml asiatic acid and 1.57 mcg/ml madecassoside were present.

A Neuroprotective Agent

Gotu Kola has been traditionally valued as a brain tonic and memory-protective herb – a reputation that has been supported by current research. The herb has antioxidant, anti-inflammatory and neuroprotective properties that affect brain function, with potential benefits for age-related memory loss and conditions such as Alzheimer’s and Parkinson’s diseases. It may even be useful for neurodegenerative disorders such as Huntington’s disease and multiple sclerosis. The research effort regarding this area of the plant’s potential has been impressive. Interestingly, some experiments have indicated that Gotu Kola can help the regeneration of nerve cells. Moreover, the herb has shown anti-epileptic (anti-convulsant) and antidepressive potential that suggest its use as an adjunct for the treatment of epilepsy and mood disorders (Orthan 2012; Xu 2012; Kumar 2011; Haleagrahara & Ponnusamy 2010; Visweswari 2010; Dhanasekaran 2009; Barbosa 2008; Gadahad 2008; Wattanathorn 2008; Xu 2008; Mohandas Rao 2007; Mukherjee 2007; Ramanathan 2007; Chen 2005; Rao 2005; Soumyanath 2005; Subathra 2005; Vattanajun 2005; Chen 2003; Gupta 2003; Veerendra Kumar & Gupta 2003, 2002).

Rosmarinic Acid

Rosemary (Rosmarinus officinalis) herb contains a number of components with anticancer properties, notably rosmarinic acid, carnosol, carnosic acid and ursolic acid (Ngo 2011).

Rosmarinic acid, which is a caffeic acid derivative, has been identified as a primary active component of Centella asiatica extracts showing anticancer (antiproliferative) activity – although other components contribute to this effect, including various triterpenes (ursolic, pomolic, asiatic and corosolic acids, etc.) (Yoshida 2005). Importantly, recent research has suggested that rosmarinic acid has a cognition-enhancing effect that indicates it could be useful for memory disorders (e.g. Alzheimer’s disease) – as well as neurodegenerative problems such as amyotrophic lateral sclerosis (Wang 2012; Bulgakov 2011). Rosmarinic acid has important pharmacological properties and rates among the most notable of the phenolic chemicals. It is prevalent in numerous aromatic Lamiaceae herbs (subfamily Nepetoideae), such as lemon balm, rosemary, sage, thyme, oregano and peppermint. This compound, which is also widespread in the Boraginaceae family, is of interest due to its antioxidant, anti-inflammatory, antiviral and antibacterial attributes. It has the potential to influence diverse inflammatory and spasmodic conditions such as asthma, intestinal disorders and allergies. Rosmarinic acid has been investigated for treating peptic ulcers, atherosclerosis, liver fibrosis, ischaemic heart disease, cataract and retinal disorders, rheumatoid arthritis and infertility (poor sperm motility) (Bulgakov 2011; Petersen & Simmonds 2003). Rosmarinic acid has also shown potent antiviral activity against Japanese encephalitis virus (Swarup 2007).


The cancer chemopreventive effect of rosmarinic acid may well impart a dietary anticancer property to the culinary use of herbs such as Rosemary and Thyme. The compound may also have valuable potential for reducing the side-effects of chemotherapy, and skinprotective effects (against UV light damage). In particular, it has been suggested that rosmarinic acid has a preventive effect against colon carcinogenesis (Karmokar 2012; Sharmila & Manoharan 2012; Bulgakov 2011). Surprisingly, some studies have found that Mints, notably Mentha spicata, generally contain a higher content (mg/g) of rosmarinic acid (19–58 mg) than Rosemary herb (7–10 mg). The level, however, can vary considerably according to the species or variety analysed. Other studies have found moderate amounts (10 mg) in Sage and Spearmint, with low levels in Lavender and Thyme (around 2 and 6.6 mg, respectively). Melissa officinalis was another good resource (36–39 mg) – although climatic and soil conditions have a significant influence on yield quality (Shekarchi 2012).

Thirteen species of Mint are found in Australia. Mentha spicata is particularly widespread, being naturalised throughout the entire continent and Tasmania. (Upper image courtesy jacilluch, flickr; lower image courtesy Charissa Lansing, flickr)

Melissa officinalis, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

Lemon Balm (Melissa officinalis) can be found naturalised from South Australia to Victoria, New South Wales and Tasmania. This herb and the essential oil have good antiviral remedy against the Herpes simplex virus with potential for clinical use (Astani 2012; Mazzanti 2008; Schnitzler 2008; Dimitrova 1993; Cohen 1964). Other familiar aromatics (oils and extracts) with similar anti-Herpes potential include Peppermint (Mentha x piperita), Sage (Salvia officinalis), Rosemary, Thyme (Thymus vulgaris) and Prunella (Prunella vulgaris) (Geuenich 2008; Nolkemper 2006; Schuhmacher 2003).

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Two rosmarinic acid derivatives are also of pharmacological importance: lithospermic acid B (salvanolic acid B) and rabdosiin. These compounds have anti-inflammatory, antioxidant and kidneyprotective properties. In particular, lithospermic acid showed significant experimental effects against diabetic nephropathy (as did rabdosiin), anticancer activity in head and neck squamous cell carcinoma, microcirculatory protection with potential in cerebrovascular and cardiac conditions, and additional cardioprotective (antiatherosclerosis) properties. Rabdosiin also had anti-HIV potential. Salvia miltiorrhiza and Lithospermum erythrorhizon are good sources of lithospermic acid B, with the latter also yielding rabdosiin (see Bulgakov 2011 for details).

Salvia miltiorrhiza (Chinese Sage) dried root. This herb, known as Dan Shen, is traditionally utilised for treating gynaecological disorders and as a cardiotonic. It is highly respected in Chinese medicine.

Gotu Kola is a rather remarkable small weed which even appears to have detoxicant attributes that support its reputation as a blood-purification agent. Investigations of the effects of the herb in arsenic toxicity showed that Gotu Kola had a significant antioxidant effect that reduced cellular damage and provided substantial support for liver function. It also had protective benefits for the kidney and brain – although it was not a chelation agent (Huda-Faujan 2007; Flora & Gupta 2007; Gupta & Flora 2006). This level of protection, which was associated with bioflavonoid components, has potential for reducing the mental effects of lead exposure in children when used in combination with a chelating compound (Ponnusamy 2008; Saxena & Flora 2006). This provides interesting support for its traditional use in China as an antidote to poisoning from wild mushrooms and Gelsemium elegans (Chang 1989). There is, however, a matter of individual sensitivity to the plant. While Gotu Kola appears to be well tolerated in most people, there are some unfortunate individuals who suffer contact dermatitis on exposure to the herb (or asiaticoside). There has also been a report of photosensitisation associated with its use (Gonzalo Garijo 1996; Bilbao 1995; Chopra 1958). While Gotu Kola has rarely been involved in reports of side-effects, it is possible that heavy metal contamination can occur (Tripathi 2012), and that individual sensitivities may involve other forms of allergic reaction. There are also a few reports of hepatotoxic reactions linked to Gotu Kola, but these do not make a lot of sense considering the strong antioxidant, anti-inflammatory and hepatoprotective properties of the herb. It is more likely this could be associated with some form of toxin contamination, herbal substitution or incorrect identification of the plant used for the raw material. For instance, various species of Germander (Teucrium spp.) have definitely been linked to hepatotoxicity.

Toxic Jessamine

Lithospermum erythrorhizon (Red Root Gromwell), Zi Cao, is primarily recommended for treating febrile and inflammatory disorders including skin eruptions, measles and burn injuries.

Gotu Kola has traditionally been utilised as a detoxicant remedy for Gelsemium poisoning. There are three species in the Gelsemium genus. All are toxic as they contain strychnine-related alkaloids (gelsemine, gelseminine) and cause a form of poisoning that has been compared to Hemlock toxicity (loss of consciousness, paralysis and death). The nectar, which will even poison


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as a criminal poison. Indeed, in December 2011 the Chinese billionaire Long Liyuan is said to have been poisoned with the drug, which was allegedly put in a cat-meat stew (BBC News Asia, 4 January 2012).

The decorative American Yellow Jessamine (Gelsemium sempervirens) is one of the toxic ornamental plants that can be found in temperate Australian gardens (New South Wales, Victoria). This vine is the basis of the well-known homoeopathic medicine Gelsemium, which has been utilised for neurological problems. (Image source: Ellis Rowan painting, from Alice Lounsberry, Southern Wild Flowers and Trees, Frederick A. Stokes Company, New York, 1901)

bees, has been linked to incidents of poisoning of children who sucked the blossoms. The depressant effect of the alkaloids once saw the herb used as a nervous system depressant with sedative, analgesic and antispasmodic properties. This also led to its popular use as an asthmatic and whooping cough remedy, albeit the risk of fatalities was high (Dobelis 1986). It was also recommended for the treatment of trigeminal neuralgia and migraine (BHP 1983) – although the homoeopathic preparation would be a much safer alternative. Gelsemium elegans, which is known as Heartbreak Grass, is from Southeast Asia and China, and has an equally toxic reputation that even led to its use

In Chinese medicine, the use of Gotu Kola (Centella asiatica) extended far beyond the European recommendations for treating wounds and skin diseases – being utilised for diverse disorders affecting the gastrointestinal, urinary and respiratory tracts. The fresh juice has been taken for uraemia, urinary problems (whitish, muddy urine), throat inflammation, and conditions characterised by agitation, chronic thirst, diarrhoea and vomiting – which is suggestive of conditions such as enteritis due to food poisoning. The decocted herb with lean pork was recommended for whooping cough, or a tea taken for measles. In infectious hepatitis the herb was decocted, sugar added, and the mixture taken twice daily for a week. An infusion prepared from the powdered herb has also been taken for pleurisy, and to ease the aches and pains associated with old wounds (Chang 1989).

Table 4.1 Summary of Recent Investigations of Centella asiatica

The table overleaf provides an indication of the remarkable amount of interest that has been expressed in Gotu Kola. This extensive range of investigations attest to the importance of Centella asiatica as a medicinal plant – confirming many of its traditional uses, as well as suggesting new avenues of therapeutic value.

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Table 4.1 Summary of Recent Investigations of Centella asiatica Medicinal properties Wound-healing studies

Antimicrobial properties

Cardiovascular and cerebrovascular

Liver (hepatoprotective)

Respiratory tract Antidiabetic potential

Radiation (radioprotective) properties

Investigations (author) Numerous studies have investigated the efficacy of Gotu Kola, asiatic acid and madecassoside as wound-healing agents (Ermertcan 2008; Kimura 2008; Liu 2008; Shetty 2006; Wollina 2006; Hong 2005; Lu 2004a, 2004b; Biswas & Mukherjee 2003; Coldren 2003; MacKay & Miller 2003; Brinkhaus 2000; Widgerow 2000; Maquart 1999; Shukla 1999a, 1999b; Sunilkumar & Shivakumar 1998; Suguna 1996). Promotion of wound healing in cases of diabetic ulcer (Paocharoen 2010). Scar management: strong wound-healing attributes for asiaticoside; can reduce scar formation (Tang 2011); clinical use of Gotu Kola for scar management and stretch marks of pregnancy (Young & Jewell 2000; Widgerow 2000). Cosmetic: extracts have been widely incorporated into creams etc. for an ability to stimulate collagen, aiming to restore skin firmness, elasticity and improve skin appearance. Extracts have also shown a mild UV protective effect (Hashim 2011). Centella asiatica extract has a very broad spectrum of antimicrobial activity. It has demonstrated antibacterial activity against Staphylococcus aureus, as well as antibioticresistant strains (MRSA: methicillin-resistant S. aureus) (Zaidan 2005). Extracts have activity against diverse gram-positive bacteria (Bacillus cereus, B. megaterium, B. subtilis, Sarcina lutea) , gram-negative bacteria (Aeromonas hydrophila, Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphi, S. typhi, S. typhimurium, Shigella boydii, Sh. flexnerii, Sh. dysenteriae, Vibrio cholerae, V. mimicus, V. parahaemolyticus) and anti-fungal activity (Candida albicans, Aspergillus niger, Saccharomyces cerevaceae) (Ullah 2009; Mamtha 2004). Antiviral potential (Zheng 1989): acts as an antiviral attachment agent against pseudorabies virus (Hosni 2006). Anti-herpes virus activity. An additive effect was seen with Mango (Mangifera indica) extracts; active components were asiaticoside and mangiferin, respectively (Yoosook 2000). Dental: use of extracts of Gotu Kola and Pomegranate (Punica granatum) significantly improved clinical signs of chronic periodontitis (Sastravaha 2005, 2003). Asiaticoside has shown particularly good effects for enhancing periodontal healing (Nowwarote 2012). Studies that have indicated the protective properties of Gotu Kola may extend to ischemia and reduction of arterial plaque. This provides support for the use of the herb as a heart tonic and for conditions such as heart attack or stroke. Madecassoside has been identified as a primary active component (Cao 2010; Bian 2008; Li 2007b; Pragada 2004; Cesarone 2001d). Gotu Kola contains cardiac glycosides that may contribute to a cardiotonic effect of the herb (Krishnaiah 2009). Gotu Kola extracts have shown cellular protective effects on the heart with potential for use in preventing the toxic side-effects of some drugs, e.g. the cardiovascular toxicity associated with the antibiotic adriamycin (doxorubicin) that is used in cancer chemotherapy (Gnanapragasam 2007, 2004). Gotu Kola contains a caffeoylquinic acid with anti-thrombotic activity (Satake 2007). Centella asiatica has shown potential for the treatment of cirrhosis and fibrosis, including bilharziainduced liver fibrosis due to the schistosomiasis parasite. Chinese investigations of asiaticoside have shown a remarkable hepatoprotective effect on chemical-induced liver injury (Zhang 2010b; Ming 2004; Kartnig 1988). Chronic hepatitis did not respond to its use (Kartnig 1988). Asiaticoside has shown experimental protective effects against septic lung injury (Zhang 2011c, 2008). Extracts have shown good potential for blood sugar regulation (Babish 2010; Krishnaiah 2009). The circulatory benefits of Gotu Kola extend to improvement of peripheral circulation in diabetic individuals (Cesaronbe 2001b, 1994). Used to promote wound healing in diabetic individuals (Paocharoen 2010). Gotu Kola has shown significant antioxidant and radioprotective potential. It acts to protect against cellular damage and normalise cellular function in radiation injuries (Joy & Nair 2009; Jayashree 2003; Sharma & Sharma 2005, 2002). Gotu Kola extracts may be valuable for treating radiation treatment side-effects involving taste perception and weight loss (Shobi & Geol 2001). An evaluation of madecassol (asiaticoside) and tetrandrine on skin radiation injuries demonstrated that both products were able to reduce acute radiation reactions due to a significant anti-inflammatory activity. Tetrandrine, a compound isolated from Stephania tetrandra and some other Stephania species, was particularly effective (Chen 1999). Note: Although S. tetrandra is not found in Australia, there are four native species of Stephania.

NEW ROLES FOR OLD REMEDIES Anticancer (anti-tumour and cytotoxicity studies)

Gastrointestinal disorders

Anti-inflammatory and antiarthritic properties

Neuroprotective (nerve protective) and mood disorders

Detoxicant (chemotoxin and heavy metal protection)

Antiparasitic and insecticidal potential

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The traditional use of Gotu Kola as an anticancer remedy has received experimental support. Extracts have shown cytotoxic and anti-tumour activity in animal studies (Babu 1995). Gotu Kola extracts: experimental anticancer activity in mouse melanoma, human breast cancer and rat glioma cell lines. Flavonoids showed antioxidant and antitumor activity (Pittella 2009). Gotu Kola extracts: apoptosis-inducing effect on breast cancer cells (Babykutty 2008), and in colon cancer studies (Bunpo 2004). Asiatic acid: induced apoptosis in numerous cancer cell lines including colon cancer (Tang 2009), and human melanoma cell lines (skin cancer treatment potential) (Park 2005). Asiaticoside: apoptosis-inducing effect; enhanced the anti-tumour activity of vincristine in cancer cells, which suggests it may be a useful adjunct in cancer chemotherapy (Huang 2004). Centella asiatica extract has shown protective activity against genotoxic agents (cyproterone acetate) (Siddique 2008). Immunomodulating and anti-inflammatory properties with chemopreventive or anticancer potential (Punteree 2005, 2004). Gotu Kola can strengthen the mucosal barrier of the gastrointestinal tract, promoting healing in gastric and duodenal ulcers and protecting against chemical injury, e.g. from aspirin or ethanol (Abdullah 2010; Guo 2004; Cheng 2004; Sairam 2001a; Cheng & Koo 2000). The herb also contains a compound (3,5-dicaffeoyl-4-malonylquinic acid) with potential for use in inflammatory bowel disease (di Paola 2010). The herb has long had a reputation as an arthritis cure. A few fresh leaves are eaten daily or it can be air-dried, powdered, and stored for later use. Studies have supported the anti-arthritic activity of Gotu Kola and suggested potential cartilage protective activity that could be useful for osteoarthritic problems. Madecassoside was identified as a significant anti-rheumatic, anti-arthritic, anti-inflammatory and cartilage protective component of extracts (Hartog 2009; Li 2009; Liu 2008a; Li 2007a). Madecassic acid has shown a more potent suppressive effect on some inflammatory mediators than madecassoside (Won 2010). Madecassol (a proprietary preparation) has had some success in the treatment of scleroderma (a chronic systemic autoimmune disease): improving joint pain (arthralgia), mobility of the fingers, and decreased skin indurations (Mowrey 1990, Kartnig 1988). Centella asiatica extracts: significant antinociceptive (analgesic) activity comparable to aspirin (but weaker than morphine), and anti-inflammatory activity comparable to mefenamic acid, a NSAID that is also used for menstrual pain (Somchit 2004); asiatic acid demonstrated analgesic and antiinflammatory activity (Huang 2011). Gotu Kola: protective effects on brain function including neurodegenerative diseases, protection for ageing process and enhancement of learning and memory (Haleagrahara & Ponnusamy 2010; Dhanasekaran 2009; Kumar 2009; Barbosa 2008; Wattanathorn 2008; Xu 2008; Mukherjee 2007; Rao 2005; Subathra 2005; Gupta 2003; Veerendra Kumar & Gupta 2003, 2002). Nerve regeneration prospects (Mohandas Rao 2007, 2006; Gadahad 2008; Soumyanath 2005). Epilepsy (Visweswari 2010; Vattanajun 2005). Anti-anxiety and anti-depressive activity (Wanasuntronwong 2012; Jana 2010; Chen 2005; Chen 2003). Asiatic acid has shown anti-ischaemic neuroprotective properties in the brain, with potential for use in rehabilitation of stroke patients (Tabassum 2012; Krishnamurthy 2009). Gotu Kola and asiaticoside-derivatives deserve serious consideration for use as neurotoxinprotective agents (Shinomol 2010; Shinomol & Muralidhara 2008a, 2008b; Ramanathan 2007; Jew 2000; Lee 2000; Mook-Jung 1999). Asiaticoside: neurotoxin protection in studies of Parkinson’s disease (Xu 2012). Gotu Kola can provide cellular protection against lead and arsenic toxicity (Sainath 2011; Ponnusamy 2008; Saxena & Flora 2006; Flora & Gupta 2007; Gupta & Flora 2006). It is, however, not a chelation agent. This hyperaccumulation effect, though, is not without risk if the plants are wild harvested from sites high in arsenic or lead (Tripathi 2012). Antiprotozoal activity against Entamoeba histolytica (Jamil 2007). Antifilarial effect: when combined with Acacia auriculiformis against Dirofilaria immitis in dogs (Jamil 2007). Intestinal helminth infections: moderate anticestodal activity against Raillietina echinobothrida (Temjenmongla & Yadav 2005). Leaf extracts showed activity against sheep fluke (Paramphistomum cervi) and larvae of malaria mosquito vector (Anopheles subpictus) (Bagavan 2009). Larvicidal and mosquitocidal activities against larvae and adults of Anopheles stephensi. Combination of Blue Gum (Eucalyptus globulus) and Gotu Kola had a synergistic effect (Senthilkumar 2009). Gotu Kola essential oil, however, showed only a mild degree of mosquito-repellent activity. The main constituents of the oil were farnesene, caryophyllene and p-cymol (Rajkumar & Jebanesan 2007).

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Remedies for Recollection

Bacopa is a small creeping, succulent herb with a fairly nondescript appearance. Native to the tropics, it is usually found on swampy lands. Australian species of Bacopa (family Plantaginaceae) include B. floribunda, B. monnieri and B. procumbens, while B. amplexicaulis is an introduction. Their preference for wet marsh-like environments is signified by the English names Water Hyssop and Thyme-leaved Brooklime. These herbs may well provide some interesting environmental benefits. Bacopa monnieri has shown arsenic chelation properties. The herb is also very cadmium tolerant, making it a good candidate for phytoremediation projects (Mishra 2011, 2006; Singh 2006). (Images courtesy Kim & Forest Starr, Hawaii)

Bacopa monnieri (syns Herpestris monniera, Brahmia indica), or Brahmi, is one of the impressive herbs of Indian therapeutic traditions that is also native to Australia. This ancient and highly valued medicinal plant was mentioned in Hindu Vedas that date back to around 5000 BC. Brahmi has been used in Ayurvedic medicine since about 500 AD for improving memory and concentration. However, there is some contention over the true identity of the herb in the ancient literature – and, while it appears Centella asiatica was also known as Brahmi in some places, it is more correctly known as Mandukaparni (Kakkar 1988; Wohlmuth 2000). Traditionally Bacopa monnieri is a highly regarded nervous system restorative that has been recommended for cases of hysteria, epilepsy, insanity and neurasthenia (nervous debility). It has a valuable tonic (adaptogenic) effect that was said to enhance vitality and promote longevity. Ayurvedic medicine also considers that Brahmi possesses diuretic, liver tonic, anti-dyspeptic and cleansing properties – hence its deployment as a blood purification herb for removing ‘poisonous affections’ and for dermatological disorders. These traditional recommendations are supported by numerous investigations. Anti-fatigue, anti-anxiety, sedative, cardiotonic, anti-ischaemic and vasoactive properties are associated with the herb’s antioxidant, cardiac, tonic and nervine effects (Anand 2011; Kamkaew 2011; Chatterjee 2010; Mohanty 2010; Kapoor 2009; Sheikh 2007; Rai 2003; Wohlmuth 2000; Kapoor 1990). Other studies have confirmed Brahmi’s antiinflammatory, anti-arthritic and wound-healing properties. The herb has good antifungal activity, as well as antibacterial activity against Escherichia coli. Brahmi contains a number of pharmacologically active components, including bacosides, bacosaponins and sterols (β-sitosterol, stigmasterol). Betulinic acid (a triterpene) is also present – which is known to be a potent antioxidant, anti-inflammatory and antibacterial agent (Viji & Helwn 2011; Sharath 2010; Vijayan 2010; Viji 2010a, 2010b; Channa 2006; Ravikumar 2005; Chaudhuri 2004). Recent investigations suggest that a triterpene component, bacosine, has a blood sugar-reducing (antihyperglycaemic) and antioxidant effect that could be of benefit in diabetes (Ghosh 2011). Investigations also indicate an effective antiulcer (mucus-protective) action in chemical and


stress-induced gastric ulceration. Studies have found that extracts had an anti-Helicobacter pylori effect that would contribute towards the herb’s efficacy (Goel 2003; Dorababu 2004; Sairam 2001b). The antispasmodic properties of Brahmi extract would also suggest that it could be useful for the treatment of irritable bowel disorders, although this remains unresolved (Altern Med Rev 2004; Yadav 1989). Brahmi has been traditionally used for treating fevers and respiratory disorders, including bronchitis and asthma. It was poulticed and applied locally to the chest for bronchitis and to ease coughing, particularly in children. Brahmi extracts have demonstrated substantial spasmolytic (antispasmodic) and bronchovasodilatory properties. The use of the herb in allergy and some forms of asthma is further supported by antihistamine properties comparable to disodium cromoglycate (Intal), a conventional anti-allergy and asthma medication. Investigations showing antiinflammatory, relaxant and immune tonic properties provide additional support for its use (Yamada 2011; Saraphanchotiwitthaya 2008; Channa 2003; Samiulla 2001; Dar & Channa 1999, 1997). In addition, Brahmi extracts have substantial hepatoprotective activity. There is a suggestion that its liver and kidney protective effects may be useful against drug-induced damage, including that associated with morphine use. It may also have the ability to enhance the analgesic effects of morphine, reducing the level of opiate drug tolerance (Bhaskar & Jagtap 2011; Rauf 2011; Menon 2010; Janani 2009; Sumathi & Niranjali Devaraj 2009; Sumathi & Nongbri 2008; Sumathi 2002; Sumathy 2001). Furthermore, the herb has shown experimental anticancer activity – with the hepatoprotective antioxidant component, bacoside A, having cancer chemopreventive effects on liver function. Triterpene saponins (bacopasides) are also of interest as antitumour components of the herb (Janani 2010, 2009; Peng 2010; Rohini & Devi 2008). The most extensive body of research on Brahmi’s therapeutic properties has involved its use as a nervine tonic, memory-enhancement and neuroprotective agent. It has significant antioxidant, anxiolytic and cognition-enhancing effects that benefit brain function. Triterpene saponins and their bacosides are the main compounds that enhance nerve impulse transmission (via repair of neuronal damage), which facilitates memory recall and retention (Vollala 2011a,

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2011b, 2011c; Altern Med Rev 2004). Clinical trials not only support its effect on memory, as improvement in related conditions can also be expected: work-related mental fatigue, epilepsy (reducing the incidence of fitting), insomnia, headache, depression, palpitations and irritability. Mental capacity in children with brain function problems and attention-deficit disorder has responded particularly well to the use of Brahmi (Morgan & Stevens 2010; Calabrese 2008; Raghav 2006; Sairam 2002; Bhattacharya 2000; Lodha & Bagga 2000; Negi 2000; Wohlmuth 2000; Kidd 1999, Tripathi 1996). The herb is more appropriate for long-term use than for short-term treatment, and supplementation for at least three months is usually recommended (Wohlmuth 2001; Stough 2001). Interestingly, Brahmi’s brain neuroprotective and antioxidant properties can extend to incidents of stroke, pesticide or aluminium poisoning, Parkinson’s and Alzheimer’s diseases (Jadiya 2011; Saraf 2011, 2010a; Shinomol & Muralidhara 2011; Singh 2011, 2010; Tripathi 2011; Hosamani & Muralidhara 2010; Uabundit 2010; Hota 2008; Limpeanchob 2008; Stough 2008; Dhanasekaran 2007; Jyoti 2007; Rehni 2007). It may also be useful as an antioxidant neuroprotectant against cellular damage due to cigarette smoke, particularly in the brain (Vijayan & Helen 2007; Anbarasi 2006a, 2006b, 2005a, 2005b, 2005c). Mentat is a combination herbal formulation that has shown some remarkable effects for mental function, particularly in children. This complex preparation contains a number of different herbs recommended in Indian traditions as adaptogens and for improving brain function. In addition to Gotu Kola and Brahmi the primary components are: Ashwaganda (Withania somnifera), Evolvulus alsinoides, Jatamansi (Nardostachys jatamansi), Amla (Emblica officinalis), Guduchi (Tinospora cordifolia), Sweet Flag (Acorus calamus) and Triphala.7 Additional herbal constituents include Ipomoea digitata, Asparagus (Asparagus racemosus) and Valerian (Valeriana wallichii). Mentat and similar formulations have demonstrated definite memory-protective and anxiety-reducing properties – as well as anti-amnesic effects (Anand 2010; Saraf 2010b; Prabhakar 2008; Vinekar 1998; Faruqi 1995; Andrade 1994, 1995; Joseph 1994; Bhardway & Srivastava 1995; Bhattacharya 1994). 7 Triphala is a combination herbal product that is composed of Chebulic Myrobalans (Terminalia chebula), Emblic Myrobalans (Emblica officinalis) and Belleric Myrobalans (Terminalia belerica) (Kapoor 1990). See also Volume 2.

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A number of clinical studies have given promising results with the use of Mentat in both hyperactive and mentally disabled children – reducing agitation, increasing the attention span, improving communication skills and scholastic performances. Associated disorders such as nocturnal enuresis (bedwetting), pica (unusual or abnormal cravings) and breath-holding spells improved significantly. There was also mild improvement in school phobia, learning disabilities and speech defects (Dave 1993; Kulkarni & Verma 1992; Koti 1991; Master & Rajguru 1991; Paranjpe 1991; Indira Bai & Sastry 1991; Seth 1991; Shah 1992, 1991; Verma & Kulkarni 1991).

Clinically, Mentat can favourably influence problems such as emotional expression, work performance, speech responses and relationship skills in schizophrenic patients (Shah 1991). The remedy has been found useful for reducing seizures in epileptic patients.8 In the treatment of mentally disabled children with epilepsy Mentat had significant benefits for controlling abnormal behaviour (hyperactivity and incongruous behaviour). It was used in addition to established antipsychotic and antiepileptic drugs. The protective action of Bacopa monnieri against drug-induced side-effects would suggest this herb has additional benefits. One study on the concurrent use of carbamazepine and phenytoin (anti-epileptic medication) with Mentat demonstrated an increased bioavailability of these drugs – which would permit the use of lower doses (Tripathi 2000; Vohora 2000; Kulkarni & George 1995; Moharana 1994; Dave 1993). The ability of Mentat to stabilise emotional responses and mental functioning has led to investigations of its use in drug withdrawal states. Alcohol withdrawal is characterised by nervous system dysfunction such as tremors, hallucinations and convulsions, as well as delirium tremens, hyper-hidrosis (profound sweating) and extreme disorientation. The protective effects of Mentat on the nervous system and brain function could even be useful for treating opiate withdrawal symptoms. Experiments have demonstrated that Mentat could prevent tolerance to the analgesic effects of morphine, thereby making the drug more effective. This suggests that it could have a beneficial role for treating opiate addiction (Kulkarni & Sharma 1994; Kulkarni & Verma 1992, 1993).

Leprosy: Disease and Disfigurement Acorus calamus. A compound preparation composed of the three herbs Centella asiatica (1 g), Acorus calamus (380 mg) and Convolvulus pluricaulis (20 mg) was trialled for the treatment of low-grade mental disability in children. These herbs have good tonic, neuroprotective and mild sedative properties. The course was long term (a year) and appreciable improvements were noted in verbal communication and concentration skills. The mixture also had an anti-anxiety effect useful for reducing hyperactivity and aggressive tendencies, thereby improving the children’s attention span (Rajagopalan 1995). (Image courtesy JeanFrançois Gaffard, CC-by-SA)

Leprosy rates among the most challenging and distressing of disorders in the history of medicine. The condition has always merited serious concern, with a diverse array of herbal remedies being used for its treatment – with varied levels of efficacy. This condition not only involves infection by a microbe that is difficult to treat, but poses numerous clinical problems. The infection can easily develop drug 8 Early research on the anti-epileptic effects of Bacopa only showed anticonvulsant effects at high doses in animal studies, some of which involved injectable formulations (Altern Med Rev 2004). However, later investigations have concentrated on different mechanisms of action which support its clinical use (Mathew 2011, 2010a, 2010b, 2010c, 2010d; Pandey 2010; Krishnakumar 2009; Khan 2008; Paulose 2008).


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Hospital. Six years later he wrote of his investigations in the Australasian Medical Gazette: At that time no medical man of the place was aware that he had seen a case of leprosy. The article in Erasmus Wilson’s book on skin diseases was in our hands, but in no work accessible to the ordinary travelling practitioner was there a plate or drawing of leprosy in any of its forms. Danielssen and Bocck’s book was out of print, and it was many years later that I had the opportunity of perusing that work in the library of the College of Surgeons, London. The illustrations there are valuable, and it is much to be regretted that no medical author in England had reproduced the plates in the class-books of the day. Had such been the case, the English medical student would have been able to diagnose ordinary well-marked cases of leprosy with readiness (Bancroft 1892).

Engraving by Gustave Doré illustrating the parable of the rich man and Lazarus (1891), from the Gospel of Luke. The beggar Lazarus, ‘full of sores’, died friendless and scorned on the steps of the rich man’s house, with only the dogs to lick his wounds. Lazarus was rewarded in the afterlife, while the rich man was not. Lazarus was later adopted as the patron saint of those suffering leprosy – an apt choice as lepers were shunned as society’s outcasts. ‘Lazar houses’, which were to become their refuge, were established across Europe during the twelfth century by the Military and Hospitaller Order of Saint Lazarus of Jerusalem. Many of the knights of this order suffered the condition.

resistance, it is contagious, and affects multiple organ systems. The integrity of the immune system is an important consideration that will affect treatment options. Complete success was virtually unknown until the advent of effective antibiotic therapy against the mycobacterium responsible (Mycobacterium leprae), and over the centuries herbal remedies were the only treatment available. It is hard to imagine the hardships faced by those who became infected, and by the clinicians who tried to ease their suffering. In the early days in Australia, the diagnosis was seriously hampered by a lack of information about leprosy. It was difficult to categorise because no one had encountered it clinically. The medical profession therefore lacked experience in treatment protocols. In 1866 Dr Joseph Bancroft began work at the Brisbane

His observations led Bancroft to diagnose leprosy in one individual – which eventually led to his interest in the control of filariasis. He initially thought that ‘leprosy and filaria were associated diseases, brought here by the Chinese, and distributed by mosquitoes carrying the diseased blood to water-tanks and elsewhere’. But while the puzzle of the transmission of filariasis and malaria were ultimately shown to be dependent on mosquitoes, leprosy was of bacterial origin.

The leprosarium on Channel Island. Australian islands were among the first choice of isolation outposts for those suffering leprosy. They included Peel Island in Moreton Bay (Brisbane), Fantome Island (Palm Island group, Townsville), and Channel Island in Darwin Harbour (Northern Territory). In 2007, Peel Island was declared the Teerk Roo Ra National Park and Conservation Park. (Image from ‘Scenes from the North Australia Patrol and other general scenes’, 1937–1942, by John Flynn, 1880–1951. Part of the Australian Inland Mission collection, c. 1912 – c. 1955)

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View of Orpheus and Fantome Islands, from Palm Island. (Courtesy Luke Duyvestyn, Wikipedia, CC-by-SA 3-0)

Remnants of the leprosarium settlement on Fantome Island. (Courtesy Debra Kerswill)

Leprosy in Australia

Leprosarium, Darwin, 1958. (Courtesy W Pederson)

The story of leprosy is always associated with tragedy. There is no real evidence of leprosy in Australia prior to the arrival of Europeans. One of the earliest cases was that of a ship’s steward in Sydney Hospital in 1853. The incidents that followed were all discovered in Chinese immigrants – in 1855 in Queensland, and three years later in Victoria. However, it was another twenty-five years before cases were recorded in the Northern Territory (1882) and, soon afterwards, in Western Australia (1888) (Britton & Hargrave 1993). It is really no surprise that those suffering this disfiguring and infectious disease were treated with disdain and banishment just about everywhere around the world. Prior to the development of effective antibiotic therapy, segregation was the only way that transmission could be controlled. Attitudes were no different in Australia. Bancroft (1892) wrote: ‘It is a matter for satisfaction that so few cases of leprosy have happened in Queensland to persons of European extraction, but there is good reason to conclude that, without the measures that are carried out to remove Asiatic and Polynesian lepers to a considerable distance from the residences of the colonists, the disease would spread amongst ourselves.’ In the southern states the segregation between European, Chinese and Aboriginal communities appears to have worked to the advantage of all concerned as leprosy failed to fully establish itself in the community. By the turn of the century, new cases in New South Wales and Victoria primarily involved immigrants and refugees, mainly from Southeast Asia, who occasionally reintroduced the disease to Australian shores. The other states showed a different pattern of infection. Queensland had an influx of cases in the late 1800s (starting in 1896) with indentured Melanesian labourers (Kanakas). Subsequently leprosy became endemic – affecting Chinese, Melanesian and European communities. A peak occurred in the 1930s, and again in the 1980s, when there were outbreaks among the Torres Strait Islanders. Between 1950 and 1990 a total 929 cases were


Article from The Star, 10 June 1891, Christchurch, New Zealand.

reported throughout the country, with 50 per cent occurring in Aboriginal people. In Western Australia and the Northern Territory, Aboriginal communities likewise suffered seriously from the disease as it was progressively passed from tribe to tribe – with a profound adverse impact on Aboriginal health. It peaked in the 1950s–1960s, after which its incidence gradually declined. Today most new cases are found among immigrants (Britton & Hargrave 1993). In the period 1991–2011 a total of 190 cases were reported Australiawide (National Notifiable Diseases Surveillance System, April 2012).

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Gotu Kola, at one time, was foremost among the herbal remedies that had a substantial reputation in the treatment of leprosy. Len Webb recorded the following in 1948: ‘A new method of treating leprosy is reported from Madagascar. A glucoside named “asiaticoside” is thought to be the active principle. It is insoluble in water, barely soluble in alcohol but dissolves well in pyridine. Solutions have been injected and the results so far are said to be remarkable. Boiteau & Grimes consider that the glucoside probably acts by dissolving waxy capsule of the Lepra bacillus, thus exposing it to attack by defensive agents of the body and other drugs.’ Asiaticoside not only had activity against Mycobacterium leprae, it was also active against the tuberculosis microbe (Mycobacterium tuberculosis) and the protozoan responsible for amoebic dysentery (Entamoeba histolytica) (Oliver-Bever 1986). Research has subsequently verified antimicrobial properties against both gram-positive and gram-negative bacteria – including Staphylococcus aureus, and its drugresistant (MRSA) forms. It has also demonstrated antifungal potential (Ullah 2009; Zaidan 2005) (see Table 4.2 for details). Asiaticoside was injected into leprotic nodules and perforated ulcers, and could be used to treat lesions that developed in sensitive areas such as around the eyes and on the fingers. In combination with antibacterial sulphonamides (formerly known as ‘sulpha drugs’) it was reported to be extremely successful in the treatment of leprosy – with clinical results comparable to the use of dapsone. Asiaticoside treatment was found useful for interstitial keratitis (inflammation of the cornea of the eye), which was said to clear completely in lepers suffering the disorder. Experimentally, asiaticoside could promote wound healing in skin tuberculosis and lupus tuberculosis (lupus vulgaris, nodular tuberculous skin lesions). Furthermore, Madecassol (a proprietary asiaticoside-containing preparation) was employed in the treatment of gangrene, and showed potential benefits for lupus erythematosus, a chronic autoimmune inflammatory disorder characterised by arthritis, fevers, skin rashes, photophobia and fatigue. Another study demonstrated that Centella asiatica was successful in the treatment of lesions due to schistosomiasis parasites when given by intramuscular injection (Kartnig 1988).

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A couple of aromatic herbs in the genus Plectranthus have been utilised for a variety of skin disorders including leprosy – P. laxiflorus (pictured here) and P. vettiveroides (Waldia 2011; Lukhoba 2006). Plectranthus amboinicus has a similar reputation, as well as being used in Brazil for treating the ulceration associated with leishmaniasis infection (Franca 1996). This herb has shown anti-mycobacterial activity that was associated with its diterpene components. Investigations continue to examine diterpenes (and derivatives) from these species for the development of drugs useful against drug-resistant mycobacteria (Rijo 2010; Frame 1998). A combination of Plectranthus amboinicus and Centella asiatica as a wound dressing to promote healing has shown good results in diabetic ulcer patients, comparable to the use of a hydrocolloid fibre dressing (Kuo 2012; Wu 2007; United States Patent 20070237841). (Image courtesy Bart Wusten)

Kemiri nuts (Aleurites moluccana), which contain a large amount of oil, were pounded to a paste for application to skin sores and ulceration.

The Leprous Affliction Ancient Nemesis in the Modern World

In Indonesia a mixture of the Beach Sunflower (Wedelia biflora), Kemiri nuts (Aleurites moluccana) and Turmeric rhizome was considered among the most effective of the traditional remedies used for leprous wounds. The Beach Sunflower has been widely used as a wound-healing agent in Southeast Asia – the leaves (or the fresh juice squeezed from them) were regarded as being highly effective (Elliott & Brimacombe 1987). (Image courtesy Phuong Tran, flickr)

Photomicrograph of Mycobacterium leprae taken from a leprotic skin lesion. (Courtesy CDC, US Government Public Health Image Library)


Leprosy has been a highly distressing affliction throughout human history. The Ancient Egyptians were familiar with it, as the disease is known to have been present in the Nile Valley before 1500 BC.9 It is even mentioned in the Bible. Since then the condition has been universally regarded with justifiable fear and loathing. It was probably introduced into Europe with the Roman soldiers, and later reintroduced by returning Crusaders. Its spread throughout the rest of the world occurred as travellers migrated from the primary focal points of infection – Africa, China and Norway. The disfiguring course of the disease has always been a great impediment to social survival for afflicted individuals. Added to this was the abject terror associated with the contraction of such a visually confronting disorder – the status of ‘outcast’ was certain, an all too terrible reality for sufferers. Contamination control was seriously hampered by the fact that some individuals could be carriers of the infection for many years before it manifested, providing an active reservoir of infection. The uncertainty regarding one’s susceptibility compounded the problem of diagnosis, treatment and preventive measures: ‘The incubation period is difficult to determine in many cases. Long exposure is required for infection, and latent infection may persist for years. Furthermore, the onset may be so insidious that early symptoms are often disregarded. Estimates extend from a few months to thirty or more years’ (Musser 1938). The incubation period of leprosy in most patients however, ranges from 3–7 years (Walsh 2010). Today, leper colonies are generally regarded as a mere memory – shunned groups of individuals suffering a condition that no longer exists. The reality of the situation is somewhat different. While leprosy is one of the oldest known diseases, its modern significance has been largely ignored – even though the health implications continue to be dramatic. At the beginning of 2000 the number of leprosy patients worldwide was over 6.5 million, in 91 countries. Considerably more are at risk of contracting the disease. In the 28 countries with the highest incidences, the

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rate is one case per thousand people. The total population of these countries is 1,320 million, and many of the inhabitants are more than likely to come in contact with the disease. The greatest concentration of cases is in Southeast Asia, particularly India. A staggering 500,000 new cases were discovered in 1990 and over 680,000 new cases diagnosed in 1999. The situation has, fortunately, improved substantially, with 244,796 new cases recorded in 2009. Over 70 per cent of the world’s leprosy sufferers reside in India, Indonesia, Bangladesh and Myanmar (formerly Burma). Brazil and Nigeria also have significant numbers of registered cases. However, authorities worry that possibly no more than one-third of those suffering from the infection have been detected in countries where health facilities are poor, and programs to diagnose the disease are equally inadequate (WHO 2010; ILEP 1994; Britton & Hargrave 1993). 9 It appears that leprosy originated in Africa and migrated to India in prehistoric times along trade routes between the Indus Civilisation, Mesopotamia and Egypt. A recent investigation of skeletal remains from northwest India has confirmed its presence here by 2000 BC – and the condition was reported in ancient Vedic scriptures (Robbins 2009).

Dr GH Armauer Hansen discovered the bacterium responsible for leprosy, Mycobacterium leprae, in 1874 – hence, leprosy is also referred to as Hansen’s disease. The microbe was found to be spread by droplet infection10, primarily via respiratory secretions: Bacilli are widely distributed in the bodies of lepers. They are found in large numbers in the skin lesions, peripheral nerves, liver, spleen, lymph nodes, kidneys and endothelium, often within ‘lepra cells’. Bacilli appear in the blood at times during fever, and are found with great regularity in the nasal secretions or scrapings of many patients. The saliva and other secretions and excretions serve as a vehicle for the exit of bacilli from the body. Lepers are regarded as dangerous only if they are ‘open’ cases, cases in which there are discharging ulcers or in whom Lepra bacilli can be demonstrated in excised tissues, 10 Mycobacterium leprae is present in the soil in some areas, which makes some animal contacts a matter of concern. Indeed, in the United States naturally-infected wild armadillos act as a reservoir for the disease (Walsh 2010).

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scrapings or in secretions or excretions. Persons with old ‘healed’ lesions like those with healed tuberculosis are no menace and need not live in strict isolation. It must be borne in mind, however, that persons regarded as cured or even persons who have never shown any evidence of the disease, may harbour bacilli. Such instances are considered as latent infections, in which the disease may flare up at any time (Musser 1938).

Much depends on the integrity of the immune system in a person exposed to Mycobacterium leprae. Remarkably, a high percentage of infected individuals can mount an effective immune response to the disease and do not develop the clinical signs of leprosy. Indeed, in most endemic areas only 5–10 per cent of infected people progress to clinical disease.11 In those who do, the status of the immune system is of paramount importance and will determine the progression of the disorder (see also Walsh 2010). There are two forms of the disease:

be affected by the mycobacterium and would benefit from herbal intervention: adaptogens such as Turmeric (Curcuma longa) and Withania (Withania somnifera) can provide general system support, while St Mary’s Thistle (Carduus marianus) and Dandelion (Taraxacum officinale) have a potent protective effect on liver function. Indeed, a study of the hepatoprotective role of an Indian herbal combination remedy known as Liv-52 has supported its traditional use for liver function in leprosy12 (Nigam 1982). For neurological dysfunction Gotu Kola and Brahmi (Bacopa monnieri) would be appropriate. Doubtless many of the traditional formulations used in treatment protocols were based on a system supportive role.

• Firstly, tuberculoid leprosy, which is the less infectious. It is associated with strong immune system defences and a limitation of skin and nerve damage. • The second form is lepromatous leprosy, where there is more extensive proliferation of the bacillus. While there are no signs at the beginning, this is much more contagious: ‘Lepra bacilli may invade any tissue or organ in the body, but, like the spirochete of syphilis, have a predilection for skin and nerve tissue. In this respect, the biologic behaviour is in contrast with that of the closely related tubercle [tuberculosis] bacillus which seldom invades skin or nerve tissue’ (Musser 1938). It is characterised by more extensive skin lesions and serious neurological damage. 11 In addition, treatment of HIV has the potential to increase the incidence of leprosy in areas where the latter condition is endemic (Walsh 2010).

Herbal Immune Tonics The benefits of immunosupportive medicines have gained greater prominence in modern medicine. Remedies such as Echinacea (Echinacea angustifolia, E. purpurea) and garlic (Allium sativa) are, once again, achieving recognition. In the case of leprosy, numerous body systems can

Turmeric (Curcuma domestica syn. C. longa), from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897.

12 Liv-52 contains Mandur Basma (iron oxide), Tamarix gallica and herbal extracts of Capparis spinosa, Cassia occidentalis, Cichorium intybus, Solanum nigrum, Terminalia arjuna and Achillea millefolium. It has gained a good clinical reputation for the treatment of cirrhosis. Its efficacy was attributed to a number of effects – diuretic, anti-inflammatory, antioxidant and immunomodulating activities (Huseini 2005).


Turmeric powder. (Courtesy Sanjay Acharya, Wikimedia Commons, CC-by-SA 3.0 Unported)

The lovely Echinacea purpurea is a premier immune-supportive remedy with an outstanding clinical reputation.

Turmeric has long been a popular household healing remedy with significant antibacterial, antiseptic and anti-inflammatory attributes. Much of this activity is linked to the main flavonoid, curcumin, and extensive research has been undertaken on its activity, particularly as an anticancer agent. Recent studies have shown that Turmeric has good antimycobacterial activity, which appears linked to curcumin and

certain derivatives, some of which have shown potential against drug-resistant Mycobacterium tuberculosis (Changtam 2010; Agrawal 2008; Leal 2003). Other species, such as the Mango Ginger (Curcuma amada), have similar potential (Singh 2010). Although it appears that virtually nothing is known about the medicinal attributes of the Australian species Curcuma australasica, it appears likely that it would have comparable antibacterial properties.

The Cape York Lily, Curcuma australasica, is found in northern Queensland (primarily Cape York), ranging to nearby sites in the Northern Territory and overseas to Papua New Guinea. The root, which has been used as a roasted vegetable by Aboriginal people, has a very similar appearance to that of Curcuma longa. The Cape York Lily was familiar to the early botanists. It was discovered by a Mr John Veitch and introduced into English horticulture, with an illustration of the herb published in the Botanical Magazine of 1867.

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Clinically, leprosy presents with a broad spectrum of symptoms. Initially they can be mistaken for common malaise: rhinitis, fever, fatigue, somnolence, headache, anaemia, vague muscle aches and pains. Skin lesions and nerve pain (neuritis) manifest to varying degrees. Eventually, progressive nerve damage results in an inability to feel properly, with a disruption of blood supply and severe muscle weakness. Later damage can affect the bones, with the development of secondary infections (osteomyelitis), while joint problems result in deformities of the hands and feet (wrist and foot drop, clawing of the toes or hands). Facial damage is particularly distressing. This includes paralysis of the facial nerve and infection of the cartilage of the nose – which may develop into a saddle-nose deformity (collapsed ‘bridge’ cartilage) and ulceration. Eye involvement also involves ulceration of the cornea – followed by infection, glaucoma or blindness. Homoeopathic preparations of Leprosinum remedy. This is utilised for conditions with a ‘leprotic’ symptomology, particularly skin conditions such as vitiligo, ringworm, skin nodules or lumps, ulceration, psoriasis, and some forms of eczema. It can also be appropriate for neurological problems (neuritis, numb-ness, tingling), hair loss, general itching (pruritis) and limb deformities, notably where there is nervous system involvement. It is particularly indicated from problems that do not respond to regular treatments (for greater detail regarding this remedy see The New Materia Medica Volume 2: New Key Remedies for the Future of Homeopathy, Colin Griffith, 2011). (Image courtesy Martin & Pleasance, Port Melbourne)

The more dramatic physical effects of leprosy can engender great disfigurement: The development of subcutaneous nodular infiltrations which often appear in the sites of the first skin eruption … The nodules most commonly involve the face, back of the hands and feet, but rarely the scalp. Loss of facial hair and beard occurs. As the nodules enlarge the skin becomes deeply furrowed; the ear lobes, lips and nose become thickened, tending to cause a resemblance to a lion’s face. The nodules appear in crops and are accompanied by leprous fever. Some may disappear, while others

continue to increase in size and cause great deformity. The infiltration may spread to other parts of the body surface. The general appearance of the skin is unhealthy. It is often dusky or ‘muddy’, dry or scaling. The nails are often striated. Ulcerations occur rather easily. Ulcers may heal, but often penetrate deeply and spread, causing appalling mutilation. Various digits may drop off. Nodular infiltrations and ulceration of the mucous membrane lead to hoarseness and aphonia (Musser 1938).

There may be associated inflammation of the kidneys and liver, tuberculosis, pneumonia and orchitis (testicular inflammation). In cases where the disease primarily affects the nervous system: [t]he nervous symptoms may appear very gradually and are most often accompanied by the development of round or irregular varicolored skin plaques … The involved areas are first hyperaesthetic [hypersensitive], later anaesthetic. Pruritis [itching] and neuralgic pains occur … Anaesthesia [loss of feeling] often commences peripherally and extends centripetally. Anaesthesia may be complete. Burns and other traumata often incite the formation of ulcers which tend to become deep and mutilating. Secretory and trophic disorders are common. Trophic ulcers of the soles of the feet are common. Atrophy of muscles occurs, often affecting the muscles of the hand. The contracture leads to the characteristic ‘claw’ hand. Gangrene or ulceration of the extremities or other portions of the body cause severe deformity (Musser 1938).

Leprosy Treatment

Dapsone is a sulfone antibiotic that was synthesised in 1908 and became the keystone of modern advances for the effective treatment of leprosy. Its development was, however, hindered by experimental toxicity until a breakthrough in 1941 led to the development of promin (a gluco-sulfone derivative) with a remarkable antimycobacterial effect. Following this, a form of dapsone (DDS: diamino-diphenylsulfone) was found to be effective. Fortunately, it had minimal side-effects and was cheap to produce. Later treatment advances lead to the development of effective antibacterial agents such as rifampicin, ethionamide/prothionamide and clofazimine. In the 1980s the World Health Organization advocated the widespread adoption of a combination antibacterial protocol that was found highly effective and continues in use today.


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This illustration shows MDT (multidrug therapy) regimens for the treatment of leprosy (World Health Organization, 2000).

The Legendary Chaulmoogra

Chaulmoogra oil (sourced from the fruit of various Hydnocarpus species, including H. pentandra) has its origins in legendary times, having been utilised by Indian medicine for more than 2000 years. Old Chinese medical texts also mention the oil, which was introduced from Siam in the fourteenth century. (Images courtesy Pierre Grard, Biotek, French Institute, Pondicherry, India)

For centuries leprosy treatments were based on the use of Chaulmoogra oil from Southeast Asia – a remedy that was employed by both Chinese and Indian medical traditions. Chaulmoogra oil deserves continued recognition as a valuable therapeutic agent

– despite the fact that the successful development of sulfone drugs in the 1940s saw its use abandoned. Initially, Chaulmoogra oil came to the attention of Western physicians in the 1850s, through the reports of Dr FJ Mouat of the Bengal Medical Service. The

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remedy gained a measure of medical acceptance – although its popularity soon waned, probably due to the revolting taste. The 1899 Squire’s Companion to the British Pharmacopoeia noted the use of ‘Chaulmugra Oil’ in a variety of conditions: psoriasis, obstinate eczema, and various irritant skin diseases, chronic rheumatism, gout and secondary syphilis. Good results were noted with its use (internal and external) for phthisis (tuberculosis). Later improvements in its preparation and administration resulted in a resurgence of interest in it as a leprosy treatment. In the 1930s the oil was once again in widespread use – and continued to be favoured until its eventual replacement by newer drugs. The general opinion regarding its efficacy is given by the Martindale Extra Pharmacopoeia (1941): Chaulmoogra oil is employed almost exclusively for the treatment of leprosy. It is not a specific, but with prolonged treatment (extending over several years) it results in so complete an arrest of the disease as to produce an apparent cure in a very considerable proportion of cases. It may be given by mouth (in capsules after meals), by intramuscular injection or by intradermal infiltration, or by a combination of these procedures. It has also been employed in pulmonary tuberculosis, but there is no convincing evidence of its clinical value, though successful results are claimed for its use by local application in tuberculous pharyngitis.

The oil was also often recommended in the treatment of syphilis. The healing value of Hydnocarpus was noted to be substantial: [it promoted] the disappearance of the macules; [with] initial swelling of the nodules, then softening, contraction, and complete cicatrization; improvement of sensation; decreased swelling of the nerves; healing of the ulcers, disappearance of the bacilli from the nasal mucus and the blood; improvement of general health. The response of early cases requires three months of energetic treatment; three to six months with moderately advanced cases (BPC 1963).

Unfortunately, the nutritional and immunological status of the patient does not appear to have been addressed. Diet can have a huge impact on health, particularly on the integrity of the immune system – therefore nutritional influences could well have been an important neglected component of the problem.

It also suggests that many herbs, which we now know have immune system supportive effects, could have played a valuable therapeutic role. There was the suggestion that Chaulmoogra oil also had anti-arthritic potential, although this was not subjected to investigation. However, there is a report by Dr Ernest Fletcher in 1940 that mentions: It was found that these ethyl esters [chaulmoogric and hydnocarpic acids] of chaulmoogra oil were of little value in either of the main groups of arthritis; and chaulmoogra oil itself was therefore tried. Small series of cases of rheumatoid or infective arthritis (which we are unable at present to distinguish satisfactorily) were not sufficiently impressive to justify its continuation and it was decided to try the oil in cases of osteoarthritis. After two years’ experience it seems that the results are sufficiently good to be set down in detail.

The treatment involved intramuscular injections into the buttocks. Initially this was a painful procedure until a local anaesthetic was incorporated. The trial was small (20 patients), but around 75 per cent responded extremely well to the treatment. The author concluded: ‘Chaulmoogra oil is found to be superior to any other single medicament in the treatment of osteoarthritis, but to have a very limited field in cases of rheumatoid or infective arthritis.’

Difficulties with Identification The Hydnocarpus genus contains over forty species of rainforest trees that range from India and Sri Lanka in the west, to the Philippines and Indonesia in the east.13 For a long time, the original source of Chaulmoogra oil was difficult to identify as, in the absence of leaf or flower samples, scientists had no real idea of the correct botanical description of the tree. Consequently the plant’s 13 In recent times the reshuffle of the Flacourtiaceae, which was a complete botanical muddle, resulted in the various genera being placed in several families. The Flacourtiaceae itself was redefined as a tribe within the Salicaceae family. The Southeast Asian Hydnocarpus was among the thirty genera previously classified in the Flacourtiaceae that were transferred to the Achariaceae. Hydnocarpus contains the greatest number of species (40) in this classification, with Ryparosa being the next largest (19). The genera Caloncoba and Carpotroche are also classified in the Achariaceae. Interestingly, fourteen Achariaceae genera are monospecific (i.e. they contain only one species), indicating that a high level of unique floral characteristics occur within this classification (Meredith Cosgrove CSIRO pers. comm March 2011; Webber & Woodrow 2005).


identification, and the subsequent isolation of the active principles, did not occur until late in the 1800s. Only a few species are suitable for use: • Kalaw, Hydnocarpus kursii (syn. Taraktogenos kurzii) from the jungles of Burma was in the greatest demand. • Tuvaraka, Hydnocarpus pentrandra (syns H. laurifolia, H. wightiana), from southern India was abundant and accessible, which led to its more widespread use.

A couple of other genera yielded oil alternatives of a similar quality to Hydnocarpus. They included (above) Godi (Caloncoba echinata, syn. Oncoba echinata) from Central Africa (Sierra Leone, Ivory Coast, Guinea), and (below) the South American Sapucainha (Carpotroche braziliensis) from the east coast of Brazil. (Upper image courtesy Susan Ford Collins, flickr; lower image courtesy Luis Bacher, flickr) Hydnocarpus kunstleri (leaf, trunk) from Sumatra and the Malay Peninsula, growing in the Flecker Botanic Gardens, Cairns. This was one of the species utilised as a Chaulmoogra oil resource in Indonesia and Malaysia. Chaulmoogra cultivation even spread to Australia, where Hydnocarpus laurifolia (syn H. wightiana) was introduced into tropical north Queensland as a plantation crop in the hope of local oil production. The tree can still be found growing in the northern suburbs of Cairns.

• The deployment of various local species depended on their availability and location. They included the Chinese Tai-fung-tze, Hydnocarpus anthelmintica (syn. H. alpina); Dudo or Dudoa (H. alcalae) was utilised in the Philippines; H. macrocarpa in southern India; Makulu (H. venenata) in Sri Lanka; and H. castanea in the Burma/Malay Peninsula region.

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Oils extracted from Hydnocarpus anthelmintica, H. wightiana, H. ilifolia and H. kurzii were regarded as having very similar anti-leprotic properties.14 The seeds had to be cold-pressed – that is, crushed and the oil extracted without the use of heat. Little appears to be known about the dietary incorporation of the oil, although its early use was severely limited by gastrointestinal irritation. Indeed, in 1922 the California State Journal of Medicine commented in an editorial: ‘This oil is, however, so nauseating and causes such serious digestive disturbances that few patients are able to continue the treatment long enough and intensively enough to obtain therapeutic results. Nevertheless, the literature records a considerable number of cases of leprosy improved, arrested and even apparently cured by this method of administration’. 14 Chopra (1956) also mentions that the seeds of H. alpina, H. octandra, H. odorata (syn. Gynocardia odorata) and H. venenata were utilised for the treatment of leprosy. Burkill (1935) adds H. ilicicolia and H. kunstleri. Hydnocarpus alpina leaf extracts have shown insecticidal (antifeedant and larvicidal) activity against the Asian armyworm (Spodoptera litura), an agricultural crop pest. The oil had a more potent activity when combined with Neem oil (Azedarachta indica) (Vendan 2010).

Gynocardia odorata, from William Roxburgh and Sir Joseph Banks, Plants of the Coast of Coromandel, Vol. 1, W. Bulmer & Co, London, 1795.

A Matter of Chemical Clarity The story of Chaulmoogra is characterised by a classic case of botanical misidentification that was to cause substantial confusion with its subsequent chemical analysis. It all began with a simple case of mislabelling. In 1879 seeds of a species of Hydnocarpus (probably H. kurzii) were wrongly labelled as Gynocardia odorata, and thus, in the older texts, the oil is often listed under ‘Gynocardia’. Chemical evaluation isolated a mixture of fatty acids, which were, quite naturally, named gynocardic acids. When the botanical differences between the seeds and the extracted oils of Hydnocarpus and Gynocardia were eventually resolved, the seed oils were found to be distinctly different. In 1881, Dr Wyndham Cottle of London experimentally used ‘gynocardic acid’ extracted from Chaulmoogra oil for the treatment of conditions such as leprosy, psoriasis, eczema and lupus. Only later, when the active compounds were properly isolated, were they named chaulmoogric and hydnocarpic

The tree Gynocardia odorata belongs to the same family as Hydnocarpus, the Achariaceae. The fruit was once, mistakenly, thought to be the source of Chaulmoogra oil. However, Gynocardia odorata oil was not found to contain chaulmoogric acid, but consisted of linolic and linolinic [sic] acids – a marked chemical difference. (Image courtesy Nandini Velho)


acids (Quisumbing 1951). Chaulmoogra oils were unique because they contained a large amount of these two acids, although the ratio in the different species could vary considerably: • Dudoa (Hydnocarpus alcalae) from the Philippines: seed oil content 65.5%, with an abundance of chaulmoogric acid (90%), and little or no hydnocarpic acid. The seed oil was used in folk medicine for the treatment of rheumatism, tuberculosis, sprains and bruising (Quisumbing 1951). • Hydnocarpus laurifolia (syn. H. wightiana): seed 32.4% oil, containing hydnocarpic acid (48.7%), chaulmoogric acid (27%), gorlic acid (12.2%), oleic acid (6.5%) and palmitic acid (1.8%) (Chopra 1956). The acids were primarily accumulated during the last 3–4 months of fruit maturation. Experimentally they had strong bactericidal effects on Mycobacterium leprae (Evans 1992). This species was particularly valued because the seeds gave a fairly high yield (twice that of H. anthelmintica) and provided a far purer oil than that derived from the other species (Burkill 1935). • Hydnocarpus anthelmintica: seeds 16.3% oil (kernel 64.8–65.5% oil), containing hydnocarpic acid (67.8%), chaulmoogric acid (8.7%), gorlic acid (1.4%), oleic acid (12.3%) and palmitic acid (7.5%) (Chopra 1956). H. anthelmintica oil was useful for scabies, scalds, rheumatism and gout. The seeds served as a vermifuge15 and as a remedy for smallpox, while the bark has been incorporated into a decoction to treat urinary incontinence (Perry & Metzger 1980). • Hydnocarpus kurzii (syn. Taraktogenos kurzii): seed 30.9% oil, containing hydnocarpic acid (22.5%), chaulmoogric acid (22.6%), gorlic acid (14.6%), oleic acid (14.6%), palmitic acid (4%) (Chopra 1956).

15 This species has shown good experimental anthelmintic activity against the roundworm, Ascaris lumbricoides (Raj 1975).

Carpotroche brasiliensis, from Flora Brasiliensis, 1886. This species, which belongs to the same family as Hydnocarpus (formerly Flacourtiaceae, now Achariaceae), contains an oil with comparable fatty acid components: hydnocarpic acid (40.5%), chaulmoogric acid (1%) and gorlic acid (16.1%). Investigations have confirmed the antiinflammatory and analgesic (antinociceptive) activity of oil extracts, thereby providing good support for the traditional uses of the remedy and its use as an anti-leprotic agent (Lima 2005). The seeds of Carpotroche brasiliensis also contain cyanogenetic glycosides (gynocardin, tetraphyllin B) (Spencer 1982).

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Ryparosa kurrangii (formerly thought to be R. javanica). Ryparosa is a small genus of nineteen trees and shrubs that range from the Andaman Islands to Southeast Asia, New Guinea and Australia – some of which yield a useful timber. (Image below courtesy Neil Hewett, Cooper Creek Wilderness, Daintree National Park)

Chaulmoogra oil, from the Martindale Extra Pharmacopoeia, 1941.

Achariaceae in Northern Australia

There are only three representatives of the Achariaceae family in Australia – all are rare species from northern Queensland. Among them is a unique native Hydnocarpus, which has been collected in the ‘Possum Scrub’ of Cape York. The two other representatives are from the rainforest: • Baileyoxylon lanceolatum from the Atherton Tablelands is the only species in this endemic genus. • Ryparosa kurrangii (formerly classified as the Javan


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Ash, R. javanica or Ryparosa sp. Daintree) has a highly restricted distribution on the Daintree coast, north of Cairns. When various genera within the Flacourtiaceae were reassigned botanically, the majority of the taxa that showed cyanogenic activity were placed in the Achariaceae family. Thus it is no surprise that the Ryparosa genus contains these compounds. Indeed, gynocardin is a specific for some species, including Ryparosa kurrangii. This cyanide-based toxin can act as part of the plant’s defensive strategies, as cyanogens are respiratory toxins that deter various herbivores. Another native tree in this family, Baileyoxylon lanceolatum, contains the same toxin in its foliage (Webber & Miller 2008). Indeed, ‘Cyanogenic defence … forms just part of a formidable physical, phenological and chemical defence continuum that exists across a [R. kurrangii] leaf age gradient’ (Webber 2005). However, the plant does not normally release cyanide, due to a separate cellular encapsulation strategy of the cyanide and the activating enzyme. They are only mixed (activated) when tissue damage occurs. The cyanide levels can vary considerably, being highest in the early floral tissue growth, in comparison to the leaf foliage. Young expanding leaves had higher levels than mature leaves – and there was significant seasonal variation. High concentrations were evident during the late wet season, with a lesser amount being found pre-wet season, when fruiting and leaf growth occurred. The latter possibly indicates its use as a stored nitrogen resource by the plant (Webber & Woodrow 2008; Webber 2007a). Mature Ryparosa leaves also produce lipid-rich food parcels (multicellular pearl bodies) that act as a reward for ants, and ‘may be invaluable for keeping long-lived leaves free from epiphyllous communities.’ This is probably a survival adaptation under the low-light conditions of the rainforest (Webber 2007b). Flower pollination appears to be primarily linked to beetle activity (Monolepta sp.), with potentially interesting aromatic attractants being utilised (Webber 2008).

Ryparosa javanica (as Bergsmia javanica), illustration by KL Blume, Rumphia, Vol. 4, 1848. Ryparosa javanica was originally thought to be a widespread species, ranging from Southeast Asia to New Guinea and Australia. It was, however, eventually determined to be a complex of at least nine species, and R. javanica itself is now considered to be confined to Sumatra, Java and Bali. Other species formerly classified as R. javanica are found in New Guinea (R. amplifolia, R. maculata, R. milleri); the Andaman and Nicobar Islands (R. kurzii); Myanmar, Thailand, Malay Peninsula and Sumatra (R. wrayi); western Borneo (R. anterides, R. maycockii); and northern Australia (R. kurrangii) (Webber & Woodrow 2006).

Baileyoxylon lanceolatum is an endemic rainforest tree of northern Queensland. (Courtesy Department of Botany, Smithsonian Institution)

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Rainforest Rescue is supporting the conservation of Cassowary habitat.

Cyanide in Pangium

There is another cyanide-containing Southeast Asian species now placed in the Achariaceae family that is of interest as a food resource – and for its poisonous reputation.16 Pangium edule is a long-lived mangrove tree that only starts to produce fruit after fifteen years. This harvest provides a good illustration of classic food-processing strategies, characterised by a great attention to detail, that have been utilised in the preparation of toxic foodstuffs. Henry Burkill (1935) recorded that: ‘The tree is poisonous enough for its name to be proverbial as an intoxicant; but the seeds are used as food, precautions being taken to prepare them in such a way as to remove the poison. The poison is hydrocyanic acid, which arises from the glucoside gynocardin, and pervades the plant. By boiling the seeds for an hour, the chemical interaction of the gynocardin and the accompanying enzyme gynocardase, by which the hydrocyanic acid is produced may be prevented; for the heat destroys the gynocardase.’ The ripe seeds contain less of the glucoside than unripe seeds, making the latter much more dangerous. 16 The toxic effects of cyanide are discussed in greater detail in Volume 3.

In many ways the survival of the Cassowary is integral to the long-term maintenance of the tropical Australian rainforest. Numerous unique native trees require transmission of their seeds through the bird’s gut for germination. This includes Ryparosa kurrangii, with germination levels improving from a mere 4 per cent (unprocessed or normal propagation strategies) to 92 per cent when passed though the Cassowary digestive system (recovered from Cassowary droppings). It was established that high levels of fruit-fly predation were linked to the poor seed-set figures, which was avoided when the Cassowary ate the fruit (Webber & Woodrow 2008; Webber 2007a). Unfortunately, there are high Cassowary fatality rates in urban and rainforest areas due to road traffic and dog attacks. Currently, few chicks survive to adulthood.


The preparation process traditionally involved crushing the seeds, boiling them and putting them into running water for a day, after which they were re-boiled before being considered edible. Another method involved the boiled seeds being buried with ashes, thereby permitting a slow natural fermentation process that took around 40 days. Various other combinations of boiling and fermentation could be utilised to reduce the time taken. However, inadequate preparation has resulted in fatalities. Burkill also mentions their use as an antiseptic, the pounded seeds used for the preservation of fish, ‘placed inside the body after the entrails have been removed and over the fish also, much as ice in Europe’. The freshly crushed seeds were applied to boils in Malaysia, while the hydrocyanide-containing leaves were used as an antiparasitic agent for itching skin problems and festering wounds. He noted that the young leaves ‘contain more poison than old ones’ – with the latter being used in Sulawesi (formerly Celebes) to make a type of condiment, the old leaves shredded, mixed with pig’s blood and salt, then stuffed into a bamboo joint and boiled. The leaves were also said to have anthelmintic properties. The tree (bark, leaves, fruit) could be used as a fish poison

Pangium edule seeds. These seeds contain a toxic oil, albeit they are utilised for culinary purposes. This was only possible when the seeds were exposed to extensive processing. Their eventual use in cooking (exposure to heat) would have finally detoxified them enough for consumption – although the seed was noted to have poor keeping qualities, quickly becoming rancid (Burkill 1931). (Image courtesy Midori, Wikimedia Commons, CC-by-SA 3.0 Unported)

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– and also as a criminal poison (Burkill 1935). In Papua New Guinea the fruit was reputed to have been used for ‘homicidal purposes’ and to assist in stealing a neighbour’s fowls by killing the birds quickly before the deed was discovered (Webber & Miller 2008).

New Roles for Chaulmoogra Oil?

Modern drugs, without doubt, have been highly effective in the treatment of leprosy – although they have not been entirely successful in actively promoting wound healing. The advent of antibiotic therapies saw the use of Chaulmoogra oil gradually fade into obscurity. Even so, the question of its efficacy has remained unresolved in current scientific terms. Surprisingly enough, during the era of its use, rigorous evaluations involving comprehensive clinical trials were never undertaken. Investigations supporting the use of Hydnocarpus oil are relatively few, considering its widespread clinical use over such a long period. However, there are suggestions that the remedy has more to recommend it than has been hitherto appreciated by modern medicine. Accounts of leprosy patients taking Hydnocarpus oil capsules as a complementary healing agent have led a few studies to attempt a re-evaluation of the oil’s potential. It can facilitate wound healing in animals and this suggests that it could be a useful addition to the treatment of leprotic ulceration. Not only can Hydnocarpus oil promote the healing process, but it also strengthens tissue repair at the wound site (Oommen 2000, 1999). There are additional reports of its topical application or oral use by individuals with diabetic ulcers and gangrene that suggest more rapid healing can be achieved (Mankrekar 1996). Centella asiatica has similar benefits for wound repair. The suggestion that combined therapies might be useful in promoting the healing of lesions is not new. The British Pharmaceutical Codex of 1963 noted that hypopigmented lesions could be encouraged to repigment by intradermal injection into the lesion using Hydnocarpus oil ethyl esters and, in nonresponsive cases: ‘when adequate bacteriological improvement is absent, a course of intradermal injections of the esters is advocated as it has been shown that such injections combined with sulphone therapy may be more effective than sulphones alone’. Traditionally, Chaulmoogra oil was primarily

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Hydnocarpus pentandra. In Kerala, India, the seed oil of this species was mixed with the leaf juice of Madar (Calotropis gigantea) and applied externally for scabies and leprosy (Silja 2008). (Image courtesy Shubhada Nikharge, flickr)

utilised for wounds and skin problems, although substantial variations in its use in folk medicine were recorded. In India, Hydnocarpus wightiana (syns H. laurifolia, H. pentandra) was specific for skin complaints, wounds, ulcers, and in treating ophthalmia (eye disorders). The seed oil provided a local application for rheumatism, sprains, bruising, sciatica and chest infections (Krishnamurthy 1959). A combination of Chaulmoogra oil and cow’s urine could be prescribed for both internal and external use. In Indian veterinary practice, Chaulmoogra oil was applied to saddle sores and provided a liniment (Kapoor 1990; Burkill 1935). In Burma, a bark decoction of Hydnocarpus castanea (H. kurzii subsp. australis) was taken for ‘internal disorders’, as well as for skin diseases (Burkill 1935). There are hints that Hydnocarpus oil may continue to have some practical value in modern therapy. While recent investigations are fairly rare, in 1983 an interesting paper mentioned that Chaulmoogra oil (and some other oils) stimulated the immune system in mice, particularly against Mycobacterium leprae. Therefore it was possible that unsaturated fatty acids could augment the chemotherapy employed in leprosy management (Wemambu 1983) – a suggestion that appears worthy of serious evaluation. Certainly, it has been shown that a combination of Hydnocarpus oil and dapsone had an additive inhibitory effect on the growth of Mycobacterium leprae (Desai & Bhide 1977). Another investigation that supports antibacterial properties for Hydnocarpus anthelmintica (syn. H. anthelminthica) seed extracts identified flavonolignans (anthelminthicins A, B, C), chaulmoogric acid and ethyl-chaulmoograte as possessing significant

Colourised scanning electron micrograph (SEM) of Mycobacterium tuberculosis. (Courtesy Janice Haney Carr, CDC)

Mycobacterium tuberculosis is an acid-fast bacterium (AFB), and is therefore undetectable when stained using a gramstain technique. However, using SEM, the M. tuberculosis bacteria glow yellow under ultraviolet light microscopy. (Image courtesy CDC)

activity against the causative agent for tuberculosis, Mycobacterium tuberculosis (Wang 2010). Flavonolignans from the genus have a variety of pharmacological properties. Those from Hydnocarpus wightiana seeds (hydnowightin, hydnocarpin and neohydnocarpin) have shown a substantial ability to lower cholesterol levels and displayed anticancer activity against a range of cancer cell types. Moreover, hydnocarpin exhibited good experimental antiinflammatory and anti-neoplastic activity in mice, as well as cytotoxic properties (Sharma & Hall 1991). Recent studies have confirmed the antiinflammatory potential of flavonolignans and have isolated a new compound (anthelminthicol A) with similar potential from Hydnocarpus anthelmintica seeds (Wang 2011). Hydnocarpus annamensis contains phenolic glycosides with anti-inflammatory and antioxidant properties (Shu 2006). Equally


interesting is the isolation of a number of cytotoxic compounds (mycoepoxydiene and derivatives, deacetylmycoepoxydiene) from a broth extract of an endophytic fungus (a species of Phomopsis) found on Hydnocarpus anthelmintica (Prachya 2007). In addition, traditional Indian medicine recommends the seed hulls of Hydnocarpus wightiana as an antidiabetic remedy.17 Investigations found extracts contained substantial amounts of hydnocarpin, isohydnocarpin and luteolin – all of which had strong antioxidant and radical-scavenging properties, as well as enzyme-inhibitory activity, that could influence the effect of the herb on regulating blood sugar levels (Reddy 2005).

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that 5’methyoxyhydnocarpin18 from this herb does not, itself, have antibacterial properties – although it can potentiate the antibacterial effects of berberine against Staphylococcus aureus. Equally intriguing was the finding that a number of berberine-containing plants were able to synthesise 5’methoxyhydnocarpin to maximise their antibacterial defences – allowing them to inactivate and overcome the bacterium’s resistance strategies (Stermitz 1999).

Hydnocarpus: Flavonoids of Pharmacological Value

Flavonoids, which have extremely diverse pharmacological potential, are the primary active components of a number of highly valued medicinal herbs. They can also interact within a plant extract in some interesting ways, about which relatively little is known. With regard to the Hydnocarpus genus, hydnocarpin and luteolin are of particular interest as both compounds have shown anticancer activity. Anticancer (cytotoxic) activity has been reported for hydnocarpin against various cancer cell lines (leukaemia, nasopharyngeal carcinoma, colon adenocarcinoma, uterine carcinoma, bone osteosarcoma) – and, importantly, it has shown a synergistic effect with the anticancer drug vincristine. This is certainly worthy of serious investigation. In addition, hydnocarpin has antioxidant (free-radical scavenging activity) and antibacterial potential against Staphylococcus aureus (Perez 2011). Hydnocarpin derivatives, which may be present in other plant genera, have shown intriguing antibacterial potentiating activity. A number of respected medicinal herbs such as Chinese Goldthread (Coptis chinensis) contain the isoquinoline alkaloid berberine (and derivatives) – which has an excellent reputation as antimicrobial agent against bacteria, fungi and protozoal infections. Interestingly, research has shown 17 Analysis of the seed hulls has isolated the following: hydnocarpin (0.08%), methoxyhydnocarpin (0.03%), isohydnocarpin (0.03%), hydnowightin (0.05%), neohydnocarpin (0.04%). The hulls also contain flavonoids, apigenin, chrysoeriol and luteolin – as well as β-sitosterol, lupeol, β-amyrin, betulinic acid and sitosterol-β-D-glycoside (Sharma 2006).

Chinese Goldthread or Huang Lian (Coptis chinensis) is an important Chinese herb with potent antibacterial, antiinflammatory, antipyretic properties. It also has substantial sedative, tranquillising, analgesic, immune-supportive and cholagogue (increase bile secretion) attributes. Significant antimycobacterial activity has been shown by berberine bisulphate from Coptis chinensis. Golden Seal (Hydrastis canadensis) is another famous medicinal herb with an antitubercular effect that is associated with this compound.

Flavonoids have attracted particular notice as antioxidants with an ability to modify or prevent free radical damage and lipoperoxidation – thereby helping to reduce the cellular damage that accompanies ageing, cardiovascular disorders or the development of cancer (Lin 2008; Seelinger 2008a, 2008b). Luteolin has a diverse range of pharmacological properties: immunomodulatory, cardioprotective, hypotensive, antioxidant, anti-allergic, antispasmodic, antiinflammatory, anti-diabetic, hormone regulating (oestrogenic, anti-oestrogenic, anti-androgenic) and anti-mutagenic activity (Lopez-Lazaro 2009; Lin 2008; Seelinger 2008a; Kotanidou 2002; Kimata 2000).

18 Small amounts of 5’methoxyhydnocarpin have been isolated from Chaulmoogra oil from Hydnocarpus wightiana

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The Chinese medicinal herb Ya Dan Zi (the fruit of Brucea javanica), which is also fairly widespread throughout the coastal regions of northern Australia, has febrifugal, antimalarial and antidysentery properties. Extracts (twigs, leaf, inflorescence) contain quassinoids with anticancer properties (bruceantin, bruceine) – the activity of which was potentiated by the flavonolignan hydnocarpin, which is naturally present in the extract. Brucea quassinoids have diverse pharmacological properties: antiparasitic, antibabesial, anti-HIV, antimalarial, antitubercular, cancer chemopreventive and cytotoxic activities (Pan 2009).

Luteolin has interesting antimicrobial and antiparasitic potential including activiity against Chlamydia pneumoniae, Candida albicans, MRSA (methicillin-resistant Staphylococcus aureus), and antiviral properties against the influenza virus (Lopez-Lazaro 2009; Xu & Lee 2001). It has also demonstrated activity against the gonorrhoea bacteria (Neisseria gonorrhoeae) and Helicobacter pylori – the latter being implicated in the development of gastric and duodenal ulceration (Chung 2001; Tsou 2001). Antiparasitic activity against Leishmania donovani (leishmaniasis) and Plasmodium falciparum (malaria parasite) is also of interest (Mittra 2000). Luteolin has substantial potential as a dietary anticancer agent with chemopreventive and chemotherapeutic properties. Not only does it show a protective role (preventing the cellular damage associated with chemical insults that result in cancer), luteolin may be of use in treating the disease and/or be suitable for use in anticancer drug combinations (enhancing drug efficacy) – as well as having radioprotective attributes that suggest its use as a protective agent for radiotherapy. Particular interest has been expressed in a significant anticancer effect on prostate cancer cells. The fact that it can cross the blood–brain barrier also suggests possibilities for brain cancer and neurological disorders (Lopez-

Lazaro 2009; Lin 2008). In addition to protective effects against nerve damage, luteolin has potential for treating multiple sclerosis and as an anti-asthmatic agent, and may be useful for the prevention of liver fibrosis (Theoharides 2009; Lin 2008; Chiang 2003; Das 2003; Su 2003; Zhao 2002; Chowdhury 2002; Ko 2002; Kobayashi 2002; Li 2001). Other studies have indicated that luteolin has xanthine-oxidase inhibitory actions with potential for use in gout, as well as inhibitory effects on lens aldose reductase, which is involved in the development of various diabetic complications. Luteolin has also demonstrated experimental cardiovascular effects – vasodilatory, hypotensive, reduced blood flow and cardiac stimulant attributes (Kim 2011; López-Lázaro 2009; Pauff & Hille 2009; Abdalla 1994; Occhiuto & Limardi 1994). Experimentally, luteolin and apigenin have shown effects on neuropsychological chemistry (via activation of monoamine transporter activity) that may well have a beneficial influence on some emotional conditions and drug dependence (Zhao 2010).

Rooibos tea. Studies of the pharmacological properties of Rooibos tea (Aspalathus linearis) found that luteolin was an important flavonoid with significant antioxidant, antimutagenic, radioprotective and anticlastogenic properties. Certainly, it is known that flavonoids are valuable tissue-protective agents for plants, including protection against UV radiation damage (Snijman 2007; Shimoi 1996, 1994). (Image courtesy Laubrau, Free Art Licence)


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Flowering Peppermint (Mentha x piperita). Parsley, celery, carrot, green peppers, artichoke, olive oil, navel oranges and various herbs (thyme, chrysanthemum flowers, rosemary, oregano, peppermint, basil, chamomile and perilla) are among the nutritional resources that provide luteolin.

Chaulmoogra: A New Cosmetic? There appears to be a continuing interest in the use of Chaulmoogra oil for skin disorders. For instance, a 1996 US Patent by Jacques LeClerq (Shiseido International, France) mentions its use in: ‘Dermatology, for harmonizing pigmentation of the skin’ (US Patent No. 5,5114,712). Chaulmoogra oil was incorporated into various formulations (emulsions, milks, oils, free or encapsulated forms) for face and body care products (day and night creams, beauty masks, foaming gels, sun products), hair care (shampoo, medicated creams, capillary lotions), and makeup (foundation creams). There is also a note regarding the use of Chaulmoogra oil for treating excessive fat build-up and cellulite.

Sapucainha, Carpotroche brasiliensis. (Courtesy Luis Bacher, flickr)

Sapucainha, Carpotroche brasiliensis. (Courtesy Luis Bacher, flickr)

Another patent by De Oliveira and colleagues in 2011 mentions similar cosmetic applications for Sapucainha oil or butter (Carpotroche brasiliensis) for use as a cosmetic (US Patent No. US2011/0038970 A1) via a process that ‘enables obtaining an improved product for use in cosmetic compositions instead of silicone and fatty esters compounds’. The story of Chaulmoogra oil provides a good illustration of the value of traditional remedies in the treatment of an extremely difficult disorder. Many remain sceptical about the usefulness of herbal extracts against bacterial infections and favour the exclusive use of antibiotic drugs. However, the evolution of drugresistant bacteria which are highly problematic in clinical situations has inspired a broader perspective, at least in some research fields. The integrity of the immune system can have a lot to do with disease progression and its severity. This situation is clearly evident with regard to leprosy – as well as another mycobacterial infection of growing importance, tuberculosis. The wider scope of activity of herbal medicines with immune-supportive properties

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suggests they could play an increasingly important role in the treatment of bacterial conditions. The fact that many herbs can be utilised with conventional drug therapies can only be to everyone’s benefit. Unfortunately, a general lack of appreciation of this in medical circles often hampers the use, and monitoring, of such innovations.

Garlic as an Anti-tubercular Agent

instance, an extract of the leaf has traditionally been utilised for treating respiratory disorders such as bronchitis, bronchiectasis of the lung, asthma, pulmonary cough, whooping cough and phthisis (an old term for tuberculosis). The use of Garlic is strongly supported by experimental evidence. Garlic’s antibacterial properties have shown definite benefits against a number of bacteria responsible for respiratory infections (bronchitis and pneumonia) such as Streptococcus pneumoniae. Garlic oil has shown a profound inhibitory effect on Mycobacterium tuberculosis, comparable to conventional antitubercular drugs such as isoniazid, p-amino salicylic acid and streptomycin. It has also demonstrated activity against drug-resistant bacterial strains, as well as antifungal and anticryptococcal properties. The latter has seen the herb utilised clinically in China for the treatment of meningitis (Hannan 2011; Gupta 2010; Dikasso 2002; Jain 1998; Kapoor 1990;

Garlic, from William Woodville, Medical Botany, James Phillips, London, 1793.

Since ancient times Garlic (Allium sativum) has been used for treating respiratory tract problems. This rather remarkable herb has significant antimicrobial and immunosupportive properties and is often recommended to boost immune system function in conditions such as tuberculosis and AIDS. While the bulb has a wellestablished medicinal reputation, other parts of the plant can be utilised in a similar manner. For

Dried garlic bulbs (Xie Bai) for Chinese medicinal use as an analgesic tonic with particular value in respiratory disorders (bronchitis), pleurisy and heart problems (chest pain, angina). It also has antidiarrhoeal properties (Yeung 1985). The purpleskinned garlic has been specifically recommended for whooping cough and tuberculosis: 30 g of skinned garlic was combined with Bai-ji powder (Bletilla striata rhizome). This was added to a rice gruel and eaten following meals, with a further 4–5 cloves taken daily for 100 days (Chang 1989).


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Delaha & Garagusi 1985). Clinically, Garlic can provide relief from dyspnoea (difficulty breathing) and improve arterial oxygenation in individuals with hepatopulmonary syndrome (Abrams & Fallon 1998).

Mycobacterium tuberculosis culture. The rough colourless surface is a characteristic typical of M. tuberculosis colonial growth patterns. (Images courtesy US CDC Public Health Image Library, Dr George Kubica)

Black Garlic is a fermented form of garlic popularly used in Asian cooking. It is believed to have tonic and longevity enhancing attributes. (Image courtesy Kok Robin at www.aziatische-ingredienten.nl)

Herbal Drugs with Activity against Mycobacteria Mycobacterial Classification Mycobacteria belong in a separate family of bacteria, the Mycobacteriaceae, in which there are several major groups. The primary ones of interest as human pathogens are those of the tuberculosis complex (M. tuberculosis, M. bovis, M. africanum and M. microti), leprosy (M. leprae, M. lepromatosis), Buruli ulcer (M. ulcerans) and AIDS-related mycobacteria (M. avium complex, M. avium paratuberculosis). There is also a rather broad category of nontuberculous mycobacteria (NTM). Numerous

non-pathogenic mycobacteria are commonly encountered in soil and water supplies and can be well tolerated by the human body. Even the tuberculosis bacteria may not cause disease (i.e. asymptomatic infection) in many individuals. However, infections with pathogenic forms of mycobacteria are notoriously difficult to treat because they possess a cellular wall structure that is highly resilient to being breached by chemicals (including detergents, antibiotics, alkali and acid compounds). In an interesting review of native New Zealand plants with anti-mycobacterial potential, Earl and coauthors provide a clear overview of the prevalence of tuberculosis (TB) infections: TB is the leading cause of death due to a single infectious organism. In 2007, 1.78 million people died from the disease and an estimated 9.27 million new cases were recorded worldwide. TB requires a lengthy treatment

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period of six months with the front-line drugs rifampicin, isoniazid, ethambutol and pyrazinamide. The availability of new drugs that shorten the course of chemotherapy would improve patient adherence and affordability, thus enabling more favourable treatment outcomes. In addition, alternative drugs are needed to counteract the spread of drug resistant TB which threatens global control programmes. MDR-TB, resistant to rifampicin and isoniazid, now exceeds 0.5 million cases per year and in some states accounts for up to 22% of TB cases. Extensively-drug resistant (XDR) strains of M. tuberculosis, resistant to both first- and second-line drugs, were first reported in the United States, Latvia and South Korea in 2006 but are now present in 57 countries (Earl 2010).

Tuberculosis has reached plague proportions in humans. In the two decades between 2000 and 2020, nearly a billion people will have become infected – with 200 million people acquiring the disease and 35 million fatalities (WHO 2000). In Australia the rate of infection is around 900–1300 cases per year, as reported between 1992 and 2011. Recent infections rates are: 1326 cases (2009), 1311 cases (2010) and 1227 cases (2011) (National Notifiable Diseases Surveillance System, April 2012). It would appear that a number of herbs with antibacterial and immunostimulant properties, some of which can be combined effectively with conventional therapies, have excellent potential for assisting in the treatment of tuberculosis. Remedies with good immunosupportive properties and a proven track record of medicinal use could well be a practical clinical blessing. The fact that Australian brushtail possums are particularly susceptible to bovine tuberculosis (Mycobacterium bovis) has been a matter of serious concern in New Zealand. Although the condition is not present in these animals in Australia (having been eradicated in the 1970s), in New Zealand they act as an environmental reservoir of the bacteria. Around 24 per cent of the possums are infected and at risk of transmitting the disease to cattle or wild deer. The introduction of these animals has been an unmitigated disaster for the country, as they have reached plague proportions (population around 60–70 million). The infection rate in cattle can be high, which has economic consequences – albeit transmission to humans is prevented due to the milk pasteurisation process, as

Common brushtail possums (Trichosurus vulpecula). (Courtesy Bryce McQuillian, Wikimedia Common, CCby-SA 2.0)

well as direct control of the infection in cattle herds (see Exotic Possums: Tuberculosis Fact Sheet, Australian Wildlife Network 2010, www.wildlifehealth.org.au). The infection rate in other countries is equally low. In the United Kingdom, fallow deer and badgers have been identified as environmental reservoirs of the disease, with controversial badger-culling programs appearing to have very limited success. In some parts of the United States, Mycobacterium bovis is endemic in white-tailed deer – although many other animals (foxes, coyotes, pigs, rodents, domestic cats) can be carriers of the disease.

Interesting New Zealand Natives A study by Earl (2010) that examined 45 New Zealand plant species determined that six were active against Mycobacterium smegmatis – a fastgrowing non-pathogenic mycobacterium that is useful for laboratory investigations. One of these, the Pukatea (Laurelia novae-zelandiae), has been utilised as an anti-tubercular remedy by the Maori, and has shown activity against Mycobacterium tuberculosis. A decoction of the inner bark was applied locally to tubercular lesions, chronic ulceration, skin problems and sores. In 1883 J White provided the following details of its use: ‘The bark of this tree is taken and the outer rind scraped off and steeped in water and used as a lotion for scrofula and obstinate running sores. A decoction of this bark


… is also used as a lotion on the parts affected by venereal disease. A very strong decoction is also taken into the mouth of the sufferer and there kept for some time in case of toothache’ (in Riley 1994). Although the infusion was also taken as a remedy for syphilis and ‘sore stomach’, there may be some reservations regarding its internal use as it is an alkaloid-rich plant that is known to be toxic to small animals – albeit human poisoning is not recorded. Perhaps this is because it was not usually taken internally, although an infusion of pulped fresh bark was mentioned as a treatment for neuralgia. Studies have shown that a bark alkaloid (pukateine) has strong analgesic properties comparable to morphine. It also contains a compound known as laureline (Brooker 1993). Interestingly, there is only one other species of Laurelia (L. sempervirens) from southern Chile, and just one closely related species, Laureliopsis philippiana – plants that attest to ancient continental Gondwanan links in floral evolution. The Atherospermataceae (Southern Sassafras) family, to which these trees belong, is well represented in Australia and New Zealand. Their essential oils tend to be characterised by safrole, which accounts for their attractive aromatic qualities, albeit there are toxicological concerns with regard to this compound (see Volume 1 for further details). Although little appears to be known with regard to the phytochemistry of Laurelia novae-zelandiae, Chilean studies of Laurelia sempervirens and Laureliopsis philippiana have shown that they contain isoquinolinic alkaloids.19 The most important component of the essential oil from Laurelia sempervirens leaves is safrole (69.3%) – which was also present in Laureliopsis philippiana (2.33%), as well as cineol (14.76%). In addition, both oils contained terpenes: 3-carene (53.81% in Laureliopsis philippiana; 2% in Laurelia sempervirens) – with low levels of ɑ-phellandrene (1–3%) and ɑ-pinene (0.4–3%). While both oils exhibited fungistatic properties, the essential oil of Laureliopsis philippiana showed

the best activity over a wide range of fungi (Bittner 2009). The safrole-rich leaf and bark essential oils of Laurelia sempervirens have shown high repellence and insecticidal activity against aphids and stored grain pests such as weevils and flour beetles (Zapata 2010a, 2010b; Bittner 2008). This would suggest that chemical evaluation of the Pukatea could yield some extremely interesting results – as could studies of related Australian Atherospermataceae (formerly Monimiaceae), some species of which are known to be rich in safrole (see Volume 1).

Pukatea (Laurelia novae-zelandiae) in bushland at the Hutt River. This slow-growing tree with fragrant leaves belongs to the Southern Sassafras (Atherospermataceae) family. It can reach 35–40 metre heights in the rainforest, forming large plank-buttresses at the base for support in shallow soil or swampy conditions – and even adopts the strategy of utilising pneumatophores (specialised respiratory roots) in waterlogged soils. (Image courtesy Pseudopanax, Wikimedia Commons, Public Domain)

19 These alkaloids were derived from aporphine, noraporphine and bisbenzylisoquinolinic-type alkaloid compounds. Other studies determined asimilobine, anonaine, and norcoridine were present in Laureliopsis philippiana. Other components of interest in L. philippiana were a phenol (1,2-dimethoxy-4-(2-propenyl)-phenol: 10.58%), while Laurelia sempervirens contained ethyl cyclohexane (1-methyl-4-1-methyl ethyl cyclohexane: 18.55%) (Bittner 2009).

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Dodonaea viscosa (and a number of subspecies, including angustifolia) are found in Australia. There are also seven naturalised Conyza species.

Antimicrobial Aromatics

Pohutukawa (Metrosideros excelsa).

Other New Zealand herbs with antimycobacterial activity are the Pohutukawa (Metrosideros excelsa), pictured here in its variegated form, and Kohuhu (Pittosporum tenuiflorum). Antibacterial prospects have also been demonstrated by Ramarama (Lophomyrtus bullata), Ngaio (Myoporum laetum) and Lancewood (Pseudopanax crassifolium) (Earl 2010). Investigations have revealed that there are a considerable number of plant-based compounds with good antimycobacterial activity – and there is plenty of scope for research. The review by Earl and colleagues (2010), as well as a number of other papers20, suggest that the antibacterial potential of many plants is underappreciated. This could be of interest for Australian resources as there are many native counterparts to the species showing good activity that remain uninvestigated. Some are certainly likely to contain similar chemical components. For instance, the South African herbal remedies Conyza scabrida and Dodonaea viscosa var. angustifolia have shown anti-mycobacterial activity (Thring 2007).

Numerous highly respected medicinal herbs possess antimicrobial properties. Conventional herbal remedies that have demonstrated a high level of antimycobacterial activity include: Guaiacum (Guaiacum officinale), Hop flowers (Humulus lupulus), Jalap (Ipomoea purga), Bitter Melon (Momordica charantia), Devil’s Club (Oplopanax horridus), Buckthorn (Rhamnus cathartica), Medicinal Rhubarb (Rheum officinale), Bloodroot (Sanguinaria canadensis), Canadian Burnet (Sanguisorba officinalis), Jambul (Syzygium jambos), Canadian Yew (Taxus canadensis) and Wall Germander (Teucrium chamaedrys). There is a renewed interest in the antimicrobial properties of spices and their culinary value as antibacterial agents. Aromatic herbs of the Lamiaceae with activity against Mycobacterium tuberculosis include Sacred Basil (Ocimum sanctum), Peppermint (Mentha x piperita), Spearmint (Mentha spicata), and Lemon Balm (Melissa officinalis) (Gatuam 2007). These herbs have been traditionally valued as antibacterial and antiseptic agents for treating infectious disorders and respiratory problems – with a good reputation for efficacy for cough relief, bronchitis, asthma, and ‘consumption’ (an old term for tuberculosis). Sacred Basil has also been utilised as an antileprosy remedy (Gatuam 2007). Other traditional aromatic medicinals with good activity include Camphor (Cinnamomum camphora), Cinnamon (Cinnamomum zeylanicum), the Common Giant Fennel (Ferula communis), Juniper (Juniperus communis, J. excelsa and J. procera) and Sage (Salvia officinalis). The Corn Mint, Mentha arvensis, is of particular interest for its antibacterial potential. Extracts have shown good activity against Chlamydia pneumoniae (now classified as Chlamydophila pneumoniae). The active components have been


Basil, dried herb. (Courtesy Finne Boonen)

including diverse Australian marsupials (notably the koala), reptiles (lizards), amphibians (frogs), and marine life (turtles) (Salin 2011). Recent investigations of Corn Mint extracts suggest that this traditional herb has a high therapeutic value. It has demonstrated substantial anti-inflammatory and sedative properties (Salin 2011; Verma 2003); antimicrobial activity against Proteus spp. urinary tract infections (Johnson 2011); and significant gastroprotective activity (Londonkar & Poddar 2009). Mentha arvensis has also shown potentiating effects in combination with antifungal drugs (metronidazol; Santos 2012) and antibiotics (gentamicin, kanamycin and neomycin; Coutinho 2009, 2008). Corn Mint is also of interest for its activity against MRSA (methicillin-resistant Staphylococcus aureus) and drug-resistant Escherichia coli, suggesting greater scope for the therapeutic use of this herb.

Flowering Corn Mint.

identified as rosmarinic acid and the flavonoid linarin – with the latter showing significant antibacterial activity.21 Chlamydia is a major cause of respiratory tract disorders such as pneumonia, sinusitis, pharyngitis and bronchitis, as well as various inflammatory disorders (meningitis, arthritis and myocarditis). Albeit a human pathogen, Chlamydia also infects animals, 21 Linarin has been linked to the pharmacological properties of a number of other medicinal herbs. It has shown interesting antioxidant and sedative activity (Valeriana officinalis, also the flavonoid apigenin; Chow 2011; Fernandez 2004); antipyretic and anti-inflammatory properties (Buddleia cordata; Martinez-Vazquez 1998, 1996); anti-amoeba potential (Buddleia cordata; RodriquezZaragosa 1999); and neuroprotective activity of potential value for degenerative neurological disorders (Mentha arvensis and Buddleja davidii; Lou 2011; Oinonen 2006).

Mint, from Paul Hariot, Atlas colorié des plantes médicinales indigènes, Librairie des sciences naturelles, Paris 1900.

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At least 50 per cent of the Queensland Koala population suffers from Chlamydia infection – resulting in blindness, respiratory infections and female infertility. Their long-term survival prospects are further complicated by the Koala retrovirus, which is rife throughout the Koala community and suppresses the animal’s immune system. (Image courtesy www.savethekoala.com)

Elecampane (Inula helenium), from Paul Hariot, Atlas colorié des plantes médicinales indigènes, Librairie des sciences naturelles, Paris 1900. Diverse herbs from the Asteraceae are of interest as antimycobacterial agents: Chrysanthemum flower (Chrysanthemum sinense), Corn Marigold (Chrysanthemum segetum, now Glebionis segetum), Elecampane (Inula helenium), Santolina (Santolina chamaecyparissus), Atlantic Goldenrod (Solidago arguta) and Canada Goldenrod (Solidago canadensis) (Newton 2000) – and the Florist’s Chrysanthemum (Chrysanthemum morifolium) (Akihisa 2005).

Australian Antimycobacterial Candidates

Wild cottage cornfield with Asteraceae herbs such as the Corn Marigold and Corn Chamomile.

The search for antimycobacterial herbs has not involved any substantial review of the Australian flora, although there are native species with good potential. A few herbs that have been of clinical importance in Aboriginal medical traditions are certainly worthy of greater interest. The Cocky Apple (Planchonia careya) is a tree with a potent antiseptic reputation that provided a healing remedy for leprosy sores, injuries and burns (even battery-acid burns) (Levitt 1981). Recent investigations have confirmed the antibacterial potential of a number of compounds


(proanthocyanidins, triterpenes and a fatty acid) in leaf extracts, with particular activity against grampositive bacteria, including Mycobacterium smegmatis, M. fortuitum and antibiotic-resistant bacteria (MRSA, VRE) – but not Escherichia coli (McRae 2008). In the Northern Territory, traditional extraction techniques were specified for the preparation of an antiseptic remedy from this tree. A thin layer from the inside bark was stripped from the trunk, twisted and then stone-hammered to break up the fibre. The pulped mass was then soaked in water and strained. The resultant lotion was said to have excellent healing properties. The remedy was applied locally as a preventative against infection following injuries such as broken fingers or bones – while bark strips from the root could be used to secure splints. The juice from the pulped roots, which was utilised similarly, was considered particularly valuable for severe injuries such as battery-acid burns. Fire-heated leaves have been applied to circumcision and spear wounds to prevent swelling, and used for treating stonefish stings. The leaf also provided an anti-itch and antiinflammatory treatment for sandfly or mosquito bites (Barr 1993; Levitt 1981).

The Cocky Apple (Planchonia careya), fruit and flowers. Cocky Apple fruit, which is also known as the Bush Mango, has been a popular bush snack. When the fruit ripens, although it remains green-skinned, it acquires a soft consistency. The flesh is only edible when it turns from white to yellow and, although it remains somewhat stringy in character, tastes something like quince (Isaacs 1994; Levitt 1981).

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In Broome (Western Australia) the remedy had a similar reputation – the stem was plastered onto sores, or a wash made from the small fine roots (mashed and soaked in water) for itching skin problems such as prickly heat, rashes and chicken pox. The bark of the root or tree was also used to prepare a bath to cure a ‘sick person’ at Arukun, Cape York (Webb 1969). Papua New Guinea the bark infusion of a related species, Planchonia papuana, has been utilised as a stomach-ache remedy (taken daily) (Holdsworth 1993). In the Solomon Islands the macerated bark and sap were drunk as a headache cure (Perry & Metzger 1980). This species has tested positive for anti-tumour activity – with alkaloids and tannins being isolated as active components (Collins 1990).

Bottlebrush (Callistemon citrinus) has shown significant antimycobacterial activity (Frame 1998). Other herbs with similar potential are the Umbrella Wattle (Acacia ligulata, bark and leaves) and the Applebush or Fruit-salad plant (Pterocaulon sphacelatum, aerial part extract) (Meilak & Palombo 2008).

The chemical links between species, genera and botanical families can be unexpected. For instance, the rare Peruvian plant pictured opposite, Clavija procera (Theophrastaceae family), has shown activity against Mycobacterium tuberculosis, with the triterpenoid aegicerin being identified as the active constituent (Rojas 2006). Aegicerin is also present in Embelia schimperi (Manguro 2006) and the River Mangrove, Aegiceras corniculatum (Zhang 2005) – which belong to a totally different family, the Myrsinaceae. The leaf decoction or juice of the latter was utilised by Australian Aboriginal people for the treatment of earache, which suggests it possesses analgesic properties (Lassak & McCarthy 1992).

The Black or River Mangrove (Aegiceras corniculatum), from Francisco Manuel Blanco, Flora de Filipinas, Manila, 1880–83.


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River mangrove (Aegiceras corniculatum).

Mallotus philippensis is a fairly widespread tree that ranges from Australia to Papua New Guinea, into southern China and India. It has been utilised for treating leprosy in Indian traditions as well as being recommended for bronchitis. Investigations have shown anti-tubercular activity (Gautam 2007). The fruit of this tree is the source of Kamala (a red powder prepared from the fruit hairs) that was once popular as an anthelmintic for treating tapeworm. It was considered particularly useful because it induced profuse diarrhoea, which rendered the additional use of a cathartic unnecessary.

Clavija procera, a rare Peruvian rainforest plant. (Courtesy Robbin Moran, New York Botanical Garden)

Mycobacterium fortuitum. Extracts of the Australian native herbs Eremophila alternifolia (bark and leaves) and E. longifolia (leaves) have shown anti-mycobacterial properties against both Mycobacterium smegmatis and M. fortuitum (for details see Chapter 7). (Image courtesy Janice Haney Carr, CDC

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Table 4.2 Plant Remedies with Antimycobacterial Potential that are Found in Australia (native or naturalised), and Closely Related Native Species There is a great diversity of medicinal herbs that have been used in India, China and Southeast Asia for treating respiratory disorders, tuberculosis or leprosy which rate serious interest for the treatment of mycobacterial disorders. Many have active wound-healing and analgesic properties. Some of these species have close counterparts in Australia, which suggests antibacterial potential for various native species. While the following list is not exhaustive (there are many more genera containing species with antibacterial activity), it does provide a serious indication of the antimicrobial potential of the native flora – much of which has not been chemically evaluated. This provides an indication of the vast untapped potential of the flora and the current lack of knowledge with regard to these resources. References utilised for medicinal uses (unless otherwise indicated) are: India (Gautam 2007); Australia (Lassak & McCarthy 1990); traditional Chinese medicine (TCM: Duke & Ayensu 1985). Species (extract and antimycobacterial activity: Gautam 2007) Abrus precatorius (stem) Crab’s Eye, Gidgee Gidgee Achyranthes aspera (plant extract)

Ailanthus altissima (syn A. glandulosa) (quassinoids: low level of activity) Tree of Heaven Alpinia galanga (rhizome essential oil) Galangal

Amorphophallus campanulatus (stem) Azadirachta indica (leaf) Bidens pilosa (leaf)

Brucea javanica (syn. Rhus javanica) (quassinoids, bruceoside-D, low-level inhibition)

Medicinal uses relating to potential antimycobacterial activity and additional notes Seeds toxic. Indian medicine: tuberculosis (tuberculous glands), respiratory disorders (asthma, cough, bronchitis), chest pain; roots used as substitutes for liquorice, used for treating catarrh and cough. Indian medicine: leprosy, respiratory disorders (bronchitis, cough, asthma, lung infections) utilised as an expectorant, skin disorders. TCM: decoction for bleeding; tincture in wine for internal injuries; analgesic. Indian medicine: asthma. TCM: leaf and stembark used for treating lung ailments; extracts bactericidal; antidysenteric. Australia: A. triphysa resin used for treating ulcers. Indian medicine: tuberculous glands, chest pain, respiratory disorders (bronchitis), sore throat, expectorant action. TCM: root used for gastrointestinal distress; antiperiodic (fevers). Indian medicine: leprosy, respiratory disorders (asthma, bronchitis, lung disorders etc.), fevers. Indian medicine: respiratory disorders (asthma, cough, phthisis, tuberculosis); leprosy. Indian medicine: pulmonary disorders, leprosy. TCM: leaf decoction anti-inflammatory and styptic, used for lung trouble; anti-inflammatory; antirheumatic; juice for treating wounds and ulcers. India, TCM: Widely utilised for treating feverish conditions and dysentery. Australia: leaves and roots used as analgesic in north Qld.

Distribution in Australia (native species) or status (naturalised/cultivated); and Australian relatives (species) Distribution: northern Qld, NT.

Distribution: WA, NT, NSW, coastal islands. Australian species: A. arborescens, A. margaretarum.

Naturalised: WA, SA, Qld, NSW, ACT, Vic. Australian species: A. integrifolia, A. triphysa. Cultivated Australian species: A. arctiflora, A. arundelliana, A. caerulea, A. hylandii, A. modesta; A. racemigera (= Pleuranthodium racemigerum). Australian species: A. paeoniifolius (syn. A. campanulatus); A. galbra. Cultivated and naturalised: NT, WA, Qld. (Melia azedarach is a closely related native species.) Distribution: east coast of Australia, SA, some islands. Additional Australian species: B. bipinnata, B. subalternans, B. tripartita. Distribution: WA, NT, Qld.

NEW ROLES FOR OLD REMEDIES Caesalpinia pulcherrima (root)

Cannabis sativa (unspecified) Canscora decussata (xanthones incl. mangiferin; total xanthones had activity comparable to streptomycin) Capsella bursa-pastoris (whole plant) Shepherd’s Purse Carica papaya (leaf) Pawpaw tree Casuarina equisetifolia (seed, leaf, stem: good levels of inhibition) Catharanthus roseus (aerial parts) Madagascar Periwinkle Cinnamomum camphora (unspecified) Camphor Tree, Camphor Laurel

Cissampelos pareira (leaf, stem: good level of inhibition) Citrullus colocynthis

Clausena excavata (coumarins)

Convolvulus arvensis (leaf)

Indian medicine: Used to treat patients with tuberculosis symptoms, bronchitis, asthma; seeds tonic and febrifuge (intermittent fevers). Other species with positive antimycobacterial activity: C. sappan also used for leprosy and asthma. C. digyna for tuberculosis (glandular, intestinal and bovine). Indian medicine: leprosy and bronchitis. TCM: seed used to treat wounds and ulcers; analgesic, antibacterial. Indian medicine: leprosy and tuberculosis.

Naturalised: Christmas I. Numerous native species: C. bonduc, C. crista, C. erythrocarpa, C. hymenocarpa, C. major, C. nitens, C. robusta, C. subtropica, C. traceyi.

Indian medicine: chest complaints; general infectious disorders, antiseptic, disinfectant. TCM: leaf ashes for fluxes, pulverised for application to sores; antidiarrhoeal. Indian medicine: expectorant. TCM and various traditions: widely used for growths and cancers; leaves for nervous pains; leaf smoked for asthma relief; latex used for wound healing. Indian medicine: diarrhoea, dysentery, stomach-ache. Australia: bark astringent for diarrhoea.

Naturalised throughout the Australian continent.

Indian medicine: cancer, antidiabetic, tonic.

India: C. camphora utilised for leprosy. India: C. zeylanicum employed for the treatment of bronchitis and has an expectorant action (leaf extract gave complete inhibition of bacteria). TCM: plant used as antiarthritic; traumatic injury; antiseptic; tumours and cancerous ulcers. Australia: C. oliveri astringent bark, tincture used for diarrhoea and dysentery. India: leprosy, tuberculosis, respiratory disorders (asthma, cough, bronchitis). TCM: root antirheumatic. India: leprosy; tuberculous glands of the neck, respiratory disorders (asthma, bronchitis).

India: fever, indigestion, malaria, colic, muscular pain, diuretic, tonic. Thai medicine: treatment of colds. TCM: leaf poultice (with other herbs) or stem bark fumigation used for ulcerated nose. India: fevers; purgative, cathartic activity. Many species have been utilised as purgative and wound healing agents. Australia: C. erubescens plant decoction used for gastrointestinal disorders (diarrhoea, indigestion, stomach pain).

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Naturalised: WA, NT, SA, Qld, NSW, Vic (widely cultivated). Australian relatives: C. diffusa: WA, NT, Qld.

Naturalised: NT, Qld and some northern islands.

Distribution: WA, NT, Qld, NSW. Other native species: C. cristata, C. cunninghamiana, C. glauca, C. obesa, C. pauper. Naturalised throughout country (except Vic and Tas). C. camphora naturalised: WA, Qld, NSW, Vic, Norfolk I, Lord Howe I. Native Australian species: C. baileyanum, C. iners, C. laubatii, C. oliveri, C. propinquum, C. virens.

Distribution: Qld.

Naturalised throughout continental Australia (not found in Tas). Related species: C. lanatus (syn. C. vulgaris) (naturalised, same distribution). Naturalised: Christmas I (as well as C. lansium). Native species: C. brevistyla, C. smyrelliana plus Clausena sp. Tipperary. Naturalised: Qld. Numerous native species: C. angustissimus, C. clementii, C. crispifolius, C. erubescens, C. eyreanus, C. graminetinus, C. microcephalus, C. recurvatus, C. remotus, C. tedmoorei, C. wimmerensis. (Note many closely related species are also classified in the genus Ipomoea).

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Conyza aegyptiaca (leaf)

India: skin diseases.

Cucurbita maxima (fruit) Cucurbita pepo (fruit) Curcuma domestica (syn. C. longa) (leaf) Drymaria cordata (whole plant) Eclipta alba (aerial parts) Elephantopus scaber (whole plant)

India: diuretic, tonic, analgesic; used in treatment of inflammation, migraine, boils, neuralgia. India: leprosy and bronchitis.

Erythrina variegata var. orientalis (syn. E. indica) (root bark)

Eugenia uniflora (leaf)

C. longa naturalised: Qld. Native species: C. australasica.

India: respiratory disorders (asthma), coughing and colds. India: leprosy, respiratory disorders (asthma, bronchitis); expectorant. India: respiratory disorders (bronchitis, cough), colds. TCM: root antidiarrhoeal and for gastroenteritis, tumours, chest pain; plant antibacterial (gonorrhoea), abscesses, influenza, pharyngitis. India: cough, microbial infections. TCM: leaf antibacterial (anti-syphilis); bark analgesic in arthritis, neuralgia, rheumatism, febrifuge, expectorant; leaf juice antibacterial and analgesic (earache, toothache). Australia: E. vespertilio: leaf decoction sedative; infusion of bast and bark used for sore eyes and headache. India: skin infections, microbial infections.

Naturalised: Qld, NSW.

India: at least 23 species are used medicinally. Australia: latex or milky juice from this weed (as well as other species) used as a wart removal agent.

Hibiscus trionum (leaf)

India: skin diseases, itching (pruritus), diuretic, stomach-ache. Australia: H. tiliaceus: inner bark and sapwood heated infusion used as antiseptic; H. vitifolius tuber used for treatment of boils. India: expectorant, chronic catarrh of lungs, cough, wound healing (antiseptic and disinfectant).

Luffa cylindrica (aerial parts)

Lygodium japonicum (whole plant)

Naturalised: WA, SA, Qld.

India: leprosy and bronchitis.

Euphorbia peplus (leaf, stem)

Hypericum perforatum (leaf, whole plant, aerial parts, flowers) St John’s Wort

Naturalised in Qld. Other naturalised species are widespread across the continent: C. bilbaoana, C. bonariensis, C. canadensis, C. leucantha, C. primulifolia, C. sumatrensis. Naturalised: Qld, NSW.

India: leprosy, bronchitis, expectorant TCM: leaf and fruit for inflammation, antibacterial – crushed leaf for abscesses, carbuncles, heat rash, swellings; fruit ash mixed with vermillion for smallpox pustules. TCM: spores used as diuretic and for treating urinary tract stones. Antibacterial properties (Yeung 1985).

Native species: E. alatocarpa, E. platyglossa, E. prostrata. Distribution: northern regions (NT, Qld). Native species: E. spicatus (same distribution). Naturalised: E. mollis (NSW, Qld). E. variegata: Qld coast, also in NT. Native species: E. fusca, E. insularis, E. lysistemon, E. numerosa, E. vespertilio. Naturalised: E. crista-galli.

Naturalised: Qld, NSW, Norfolk I. E. brasiliensis: naturalised (Qld). Native species: E. reinwardtiana (WA, Qld coast). Naturalised throughout the southern part of the continent (ranges from WA to SA, southern Qld, NSW, inland Vic and throughout Tas). There are numerous native and naturalised Euphorbia species (around 70, including a number that have not been botanically categorised). Distribution: found throughout the continent (including Tas). Around 50 species found in Australia, the majority are native. Naturalised: 19 species are found in Australia, many are naturalised; H. perforatum is the most widespread, found throughout the continent (including Tas). Native species: H. gramineum, H. japonicum (not NT), H. pusillum (Tas only). Native species: L. aegyptiaca (syn L. cylindrica) WA, NT, Qld; L. graveolens (WA, NT).

Naturalised NT, Qld, NSW. Native species: L. flexuosum, L. microphyllum, L. reticulatum.

NEW ROLES FOR OLD REMEDIES Mallotus philippinensis (bark) Kamala Tree

India: leprosy, bronchitis. TCM: fruit bactericidal; used for treating colds, skin disorders, ringworm, scabies, herpes, tumours. Australia: M. mollissimus milky sap with coconut juice as dysentery cure.

Mangifera indica (leaf)

India: respiratory disorders (asthma, bronchitis, cough, throat troubles). TCM: Leaf ashes for burns and scalds, burning leaf smoke inhalant for respiratory disorders (asthma, cough) and skin problems; bactericidal and fungicidal. India: expectorant, bronchitis. TCM: oil inhalant for colds, coughs, rhinitis; oil drop on sugar for cholera, colic, anodyne, antiseptic. Australia: extensive medicinal uses; wide use as antiseptic agent (see also Volume 2). India: leprosy, asthma.

Melaleuca leucadendron (essential oil)

Mimosa pudica (leaf) Momordica charantia (leaf)

India: leprosy, respiratory tract (asthma, bronchitis, expectorant). TCM: antidiabetic.

Morinda citrifolia (leaf)

India: tuberculosis, respiratory disorders. Australia: rootbark infusion antiseptic.

Passiflora foetida (stem) Stinking Passionfruit

India: asthma.

Physalis angulata (aerial parts)

India: gastric disorders, diuretic, earache, tumours.

Plantago lanceolata (leaf, root, flowers, sap)

India: respiratory disorders (cough, pulmonary diseases; expectorant).

Plantago major (whole plant; leaf) Plantago

India: leprosy.

asthma,

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Distribution: NT, Qld, NSW. Additional native species: M. claoxyloides, M. discolor, M. dispersus, M. ficifolius, M. megadontus, M. mollissimus, M. nesophilus, M. paniculatus, M. polyadenos, M. repandus, M. resinosus, M. surculosus. Naturalised: WA, NT, Christmas I, Qld, NSW. M. odorata naturalised (Christmas I).

= M. leucadendra: native to Qld, NT, WA. Around 269 Melaleuca species are found in Australia (some of which may be reclassified at Callistemon at a later date). Naturalised: NT, Qld, NSW, Christmas I. Naturalised: M. diplotricha (Qld), M. invisa (Christmas I), M. pigra (NT, Qld). Distribution: Qld, Christmas I. Naturalised: NSW. Additional native species: M. balsamina, M. cochinchinensis. Distribution: coastal Qld, NT, WA and nearby islands. Additional native species: M. acutifolia, M. ammitia, M. bracteata, M. canthoides, M. constipata, M. jasminoides, M. podistra, M. reticulata, M. retropila, M. salomonensis (now Coelospermum paniculata var. syncarpum), M. umbellata. Naturalised: WA, NT, Qld, NSW, Christmas I, Cocos (Keeling) Is. Numerous naturalised species: P. caerulea, P. coccinea, P. edulis, P. filamentosa, P. laurifolia, P. maliformis, P. morifolia, P. quadrangularis, P. sanguinolenta, P. suberosa, P. subpeltata, P. tarminiana. Native species: P. aurantia, P. aurantioides, P. cinnabarina, P. herbertiana, P. kuranda. P. angulata (‘Native Gooseberry’) may be pre-European introduction in NT. Otherwise considered naturalised throughout the country. Naturalised: P. alkekengi, P. cinerascens, P. crassifolia, P. hederifolia, P. ixiocarpa, P. lanceifolia, P. longifolia, P. micrantha, P. minima, P. peruviana, P. philadelphica, P. pubescens. Naturalised: NSW, Vic, SA, WA, Qld, Tas (not NT). Numerous species (around 37) found across the continent; the majority are native. Naturalised: NSW, Vic, SA, WA, Qld, Tas (not NT).

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Portulaca oleracea (leaf)

India: leprosy, asthma, cough. Australia: nutritive and blood-cleansing attributes; mild diuretic; antiscorbutic.

Prunus domestica (leaf) Prunus persica (stem)

India: digestive disorders (aperient), laxative, gynaecology (irregular menses, leucorrhoea). India: respiratory disorders (cough, bronchitis, expectorant). TCM: leaf febrifugal for cholera and typhoid; kernel used as antitussive agent, antibacterial for carbuncles, febrifuge for ague, cough. India: cough. TCM: leaf, flower and fruit antibacterial; fruit extract anti-Salmonella; antidiabetic agent.

Psidium guajava (stem) Guava Punica granatum (whole plant) Pomegranate

Ricinus communis (whole plant) Castor Oil plant

Rubus fruticosus (aerial parts) Raspberry

India: respiratory disorders (bronchitis, cough, sore throat, chesty troubles). TCM: antidysenteric agent; anthelmintic; antibacterial, antiparasitic, astringent, antiviral (Yeung 1985). India: leprosy, asthma, bronchitis. TCM: leaf and root decoction antiarthritic, antitussive and expectorant, facial palsy; heated leaves to treat gout and swellings; powdered seed antibacterial (abscesses, boils, carbuncles, other skin disorders). India: wound-healing, antiseptic and disinfectant qualities; whooping cough.

Salix alba (unspecified)

India: diarrhoea, dysentery (astringent), rheumatism, tonic.

Sida acuta (leaf)

India: gastric disorders and stomach-ache, back pain, boils, burns, tonic; fever, nervous problems, urinary tract disorders. TCM: leaf decoction for influenza; plant to treat boils, cough, cuts, fevers antibacterial (gonorrhoea); antirheumatic. India: respiratory problems (cough, phthisis, throat diseases). TCM: plant used to treat bruising and swellings; widely used elsewhere for respiratory disorders (cough, asthma), fevers, paralysis (hemiplegia), inflammation; sores, ulcers, antirheumatic; antidysenteric. Australia: S. rhombifolia (syn. S. retusa) plant eaten for indigestion, root decoction for diarrhoea; Europe: used for tuberculosis and as antirheumatic.

Sida cordifolia (unspecified)

Distribution: throughout Australia. Total of 22 native species: P. australis, P. bicolor, P. clavigera, P. conspicua, P. decipiens, P. digyna, P. filifolia, P. intraterranea, P. napiformis, P. oligosperma, P. pilosa, P. tuberosa (plus a number of unnamed spp.). Naturalised: P. grandiflora. Cultivated and naturalised: SA, NSW, Vic, Tas. Cultivated and naturalised: WA, SA, Qld, NSW, Vic, Lord Howe I.

Cultivated and naturalised; Qld, NSW, Lord Howe I, Christmas I, Norfolk I. P. cattleyanum and P. guineense also naturalised. Cultivated and naturalised: SA, Qld, Lord Howe I.

Naturalised across the continent and islands (not Tas).

Naturalised: a surprising number of other species have been naturalised across the continent. Total number of species: 38. Native species: R. fraxinifolius, R. gunnianus, R. moluccanus, R. moorei, R. nebulosus, R. niveus, R. parvifolius, R. probus, R. pyramidalis, R. queenslandicus, R. radula, R. rosifolius. Cultivated and naturalised SA, NSW, Vic, ACT. A number of other Salix species (total 16 spp.) and numerous hybrids are also naturalised. Naturalised: WA, NT, Qld, NSW, Christmas I and the Cocos (Keeling) Is. Numerous species (total 39 spp.) are found across the continent; the majority are native.

Qld, NT, WA.

NEW ROLES FOR OLD REMEDIES Solanum dulcamara (leaf, whole plant) Bittersweet

Solanum tuberosum (leaf) Potato plant Stellaria media (leaf, whole plant) Chickweed

India: leprosy; respiratory disorders (chronic bronchial catarrh, asthma, whooping cough). TCM: stem antiarthritic, anti-asthmatic, whooping cough; vinegar-marinated berries applied to cancerous sores and swellings. India: cough.

Naturalised: Tas. There are numerous native and naturalised species (total 186 spp.) See Chapter 12.

India: bone fractures, sprains, astringent. TCM and elsewhere: widely used for skin disorders (eczema, psoriasis, sores, ulcers, swellings, warts); wounds; anticancer (tumours); febrifuge; antirheumatic (analgesic).

Naturalised throughout the continent (incl Tas) and islands. Native species: S. angustifolia, S. caespitosa, S. filiformis, S. flaccida, S. glauca, S. multiflora, S. parviflora, S. pungens. Naturalised: S. graminea, S. pallid. Cultivated and naturalised in Qld. There are numerous native species of Syzygium (around 76, including a number of naturalised species). Naturalised: NSW, Qld. Also naturalised: T. patula.

Syzygium jambos (= Eugenia jambos) (leaf) Jambu Tagetes minuta (aerial parts) Stinking Roger Taraxacum officinale (leaf) Dandelion

India: cancer, colic, diabetes, diarrhoea, dysentery, tonic.

Terminalia catappa (stem) Beach Almond Typha latifolia (leaf) Vigna marina (= V. lutea) (aerial parts)

India: leprosy and bronchitis. Australia and Oceania: extensive medicinal uses (see also Volume 2). TCM: leaf used as vulnerary (healing agent); flower analgesic (menstrual disorders), anti-inflammatory. Australia: V. vexillata roots chewed and eaten for constipation.

Xanthium strumarium (whole plant, aerial parts)

India: cancer, wounds, malaria, headache, ulcers, rheumatism. Elsewhere (Duke & Ayensu 1985): antibacterial (syphilis, skin infections), skin disorders (abscess, boils), febrifuge, smallpox, infections, respiratory disease (asthma, colds, sinusitis, rhitinitis); analgesic, antiarthritic, anti-herpes (shingles), tumours, wounds. India: respiratory disorders (cough, asthma).

Zizyphus mauritiana (root)

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India: wound-healing, bronchodilatory activity.

antiseptic,

disinfectant;

India: phthisis (TB). Europe: used as a liver tonic and diuretic remedy.

Cultivated and naturalised: WA (southeast), NSW, Vic, SA.

Naturalised. Also naturalised: T. hepaticolor, T. koksaghyz, T. khatoonae, T. squamulosum. Native species: T. aristum, T. cygnorum. Distribution: tropical Qld and NT. There are numerous native species of Terminalia (around 30 spp.) Naturalised: NSW, Tas. Native species: T. domingensis, T. orientalis. Distribution: coastal NSW, Qld, NT. Native species: V. angularis, V. canescens, V. hosei, V. lanceolata, V. luteola, V. radiata, V. suberecta, V. unguiculata, V. vexillata (plus a number of unnamed and naturalised spp.). Naturalised: throughout the continent (not Tas). X. spinosum is also found naturalised in Australia.

Distribution: Qld, NT. Native species: Z. oenopolia, Z. quadrilocularis.

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A stand of tropical eucalypts.

The Eucalypt has long been valued for the treatment of respiratory disorders, including tuberculosis. Indeed, the Eucalypt is one of the most popular remedies for the treatment of tuberculosis in Uganda (Tabuti 2010). This is probably largely due to the decongestant, antispasmodic and antibacterial effects of 1,8-cineole. However, studies of Eucalyptus botryoides, E. camaldulensis, E. citriodora, E. deglupta, E. globulus, E. grandis, E. maculata and E. tereticornis have shown only very weak antimycobacterial properties (Newton 2000). Some Eucalypts do contain oleanic and ursolic acids, which have a broad spectrum of anti-mycobacterial activity (Bamuamba 2008). They include the Forest Red Gum (E. tereticornis), Blue Gum (E. globulus) and the River Red Gum (E. camaldulensis subsp. obtusa). Ursolic acid has also been found in Tea Tree (Melaleuca leucadendra) extracts (Chen 2002; Siddiqui 2000; Patnaik 1991). Therefore, some species may be more useful than others as antimycobacterial agents. It is equally likely that different types of preparation and extraction procedures would influence their antibacterial potential.

Eucalyptus globulus, from RG Baker & HG Smith, A Research on Eucalypts, Technical Museum, Sydney, 1920.

 The age-old reputation of many plant products as antibacterial or wound-healing agents is obviously well deserved. Even Cannabis, a herb that is under intense cultivation in many parts of Australia, has significant antibacterial properties. However, there is a diverse array of other natural products with equally interesting potential. It may come as a surprise to find that the most potent, and medicinally valuable, antibacterial agents were sourced from common old earth. Mud poultices have been a traditional wouldhealing remedy since ancient times across the globe, as were mouldy fruits and grains – and with good reason. Investigations were to find that various soilderived fungi rated highly as antimicrobial resources. Indeed, over time, the search for antibacterial agents has evaluated an inconceivable range of soil microorganisms, fungi and fruit-derived moulds. The results have been spectacular, providing the foundation for the practice of medicine as we know it today.


Cannabis: An Ancient Antibacterial Agent

Cannabis seeds and leaf.

Cannabis leaves. (Courtesy Farmer Dodds, flickr)

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have Historically, Marijuana has been widely used as a potent analgesic, antibacterial and anti-inflammatory remedy. Over the centuries, these effects would have influenced the practical use of cannabis in folk medicine. Certainly, it is effective for the treatment of a vast array of conditions, including its use as an analgesic in cancer. Research has substantiated many traditional recommendations, mainly (but not exclusively) linking the effects of Cannabis to its cannabinoid components.22 Cannabidiol has attracted particular interest as an anticancer agent (Appendino 2011). A number of cannabinoids have significant anti-infective properties. For instance, THC (tetrahydrocannabinol) has demonstrated inhibitory anti-viral activity against Herpes simplex, even at low doses (Blevins & Dumic 1980). Cannabidiol, cannabigerol, cannabidiolic acid and cannabigerolic acid have shown antibiotic properties (ElSohly 1982). A 1960 report stated: ‘Noteworthy is the effect upon Staphylococcus aureus strains which are resistant to penicillin and to other antibiotics … That was one of the peculiar properties of cannabis which was found to be most attractive. We saw the possibility of using the antibiotic action locally, without any danger of producing resistant strains to other antibiotics administered at the same time throughout the treatment’ (Kabelik 1960). It proved effective against the causative agent of tuberculosis (Mycobacterium tuberculosis) – as well as a wide range of pathogenic bacteria (Staphylococcus, Streptococcus, Enterococcus, Corynebacterium and Bacillus). Resin extracts inhibited Mycobacterium tuberculosis down to a dilution of 1:150,000 – as well as having a remarkable inhibition of S. aureus haemolyticus, even at 1:1,000,000 dilution (Kabelik 1960). Experimentally, the 22 Over 500 different compounds have been isolated from Cannabis sativa – around 100 of which are cannabinoids, while another 120 are terpenoid-based. In addition, polyketides, modified sugars, alkaloids, flavonoids, stilbenoids and quinones are present (Appendino 2011). Cannabinoids (cannabigerol and its acid) have also been isolated from the African herb Helichrysum umbraculigerum, with related compounds being found in the New Zealand liverwort Radula marginata – although little is known about their phytochemistry (Appendino 2011).

[[cap

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main cannabinoids (THC, cannabidiol, cannabinol, cannabichromene, cannabigerol) have shown good activity against drugresistant Staphylococcus aureus (MRSA). Cannabinoids (THC, cannabidiol, cannabinol) also possess significant anti-inflammatory properties (Appendino 2011). Indeed, THC has demonstrated activity twenty times more potent than aspirin and twice that of cortisone (Formukong 1989). Current research has focused on the development of drugs for the treatment of nausea and anorexia (particularly that associated with chemotherapy), conditions associated with pain and inflammation, insomnia, glaucoma, and spasticity from spinal injury. Some cannabinoids also have neuroprotective properties that may be of clinical value. THC has been proposed as a neuroprotective agent

in Parkinson’s disease, while some cannabidiol analogues may have a protective role against optic nerve damage (Appendino 2011). Indeed, experimentally THC and cannabidiol can both enhance the penetration of various drugs into the brain (Reid & Bornheim 2001). Cannabidiol can help with pain relief and spasticity in the treatment of conditions such as multiple sclerosis and amyotrophic lateral sclerosis (Appendino 2011). This is of interest as morphine and THC have very similar pharmacological properties, despite a different mechanism of action (Rapaka & Sorer 1994). Therefore it is not too surprising to find that a recent clinical study of the treatment of pain with opioids and inhaled cannabis suggests that this combination had a significant enhanced analgesic effect – which may well help address the problems with opiate addiction and tolerance in individuals on long-term drug therapy (Abrams 2011).

Chapter 5

EARTH MEDICINE: A MINERAL PHARMACY Numerous seemingly improbable remedies have been used by ancient cultures – some of which involved odd practices. Despite sounding somewhat farfetched, quite a few were ultimately shown to contain an element of truth. The search for antibacterial agents involved experimentation with various unusual remedies – and their exposure to the scrutiny of modern chemical studies has revealed some rather surprising results. In ancient cultures, commonly available items such as beer and honey were popular antibacterial remedies that were found helpful for the treatment of abscesses, sores and boils (Nunn 1996). The yeast in beer sediment is rich in vitamin B and contains antimicrobial components – properties that tend to support its use in intestinal complaints and skin diseases.

Physicians in many cultures had long observed that mould could be used as a wound-healing agent. Mouldy bread was deployed in many folk-healing traditions, including that of Ancient Egypt, where it was recommended for treating blisters, intestinal disorders and pus-forming wounds. In 1908, Dr AE Cliffe, a Canadian biochemist touring in central Europe, noted: ‘I came across the fact that almost every farmhouse followed the practice of keeping a mouldy loaf on one of the beams in the kitchen. When I asked the reason … I was told that this was an old custom and that when any member of the family received an injury such as a cut or bruise, a thin slice from the outside of the loaf was cut off, mixed into paste with water, and applied as a bandage. It was assumed that no infection would result from such a cut’ (Lechevalier & Solotorovsky 1965). Much later it was established that the characteristic blue-green discoloration seen on mouldy bread was the useful antibiotic-producing Penicillium mould. Across the world, other antibacterial folk remedies have included mouldy jam (Canada), chewed apple or barley allowed to grow mould (central Asia), mouldy corn soaked in water or date wine (Jewish traditions), mould scraped from cheese (Ancient Greece), and mouldy soya bean paste (China). King James I’s personal herbalist, John Parkington, advocated the use of mould in 1640 in his Theatrum Botanicum. Other English traditions tell of the use of mouldy porridge, wheat straw and oranges, rotten apples, green leather (old boots), and mouldy ham and/or bacon fat (Wainwright 1989a, 1989b; Bickel 1971; Kavaler 1962). All these recommendations exploited the mould’s natural antibacterial principles. A letter to Professor of Biology Milton Wainwright (1989b) from a Mr D McCarthy of Hull (County Cork, Ireland) recounted:

The Ebers Papyrus (around 1550 BC), discovered in 1873–74 by George Ebers, is among the most important medical texts of the Ancient Egyptians. (Courtesy Einsamer Schütze, Wikimedia Commons, CC-by-SA3.0 Unported)

Many years ago an old aunt of mine (who was some 82 193

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years old), who appeared to be quite learned in ‘cures’, read one day in a magazine of Professor Fleming’s discovery of penicillin which was described as result from research on a mould. My aunt said in her own inimitable way ‘I had that cure before he had!’ I know that one of her cures was to collect ten to twelve oranges and place them somewhere they would get mouldy as soon as possible. She would then carefully remove the greenish mould and make it into some form of concoction/defusion/infusion and use it on abscesses, whitlows, boils, or other forms of pustule. She would also administer it orally, and all apparently with complete success. Mouldy oranges once provided a household antibiotic remedy for all types of wounds and infections.

A similar remedy was used by the grandfather of Mrs L Collingwood (also of Hull, Ireland) in the 1920s: ‘If we had nasty sore knees, grit and scabs from falling down, he used to get his penknife and cut and scrape the ham or bacon side hung from the ceiling (to be cured), salted and green and put the fat on a piece of clean linen and grandma used to wrap our knees up and it always cleansed and healed our wounds.’ Aboriginal healers used moulds sourced from the sheltered side of Eucalypt trees to treat wounds (Kavaler 1967). Certainly, Australian bushmen knew of this practice, with one travelling to Melbourne to give the Walter and Eliza Hall Medical Institute1 ‘a smelly bundle of moulds wrapped in sacking’, with the suggestion that they should be investigated because ‘they appeared to defeat infection and promote healing’ (Wainwright 1989b; Bickel 1972). An interesting case history of the 1920s regarding a treatment for impetigo (a skin disease due to Staphylococcus aureus) mentioned the use of a mouldy starch-impregnated face mask and wraps on affected areas. In Sheffield (England), a Dr Twomey recommended the use of a starch mix that had been allowed to turn mouldy: ‘On his return Twomey found, as he had expected, that the surface of the starch was covered with a luxuriant growth of green mould. Next, he told Brenda’s mother to scrape out 1 This was the first medical research institute established in Australia, opened in 1915 by Eliza, widow of Walter Hall, a rich transport, livestock and mining entrepreneur.

the mouldy starch and apply it to a mask placed over the young girl’s face so that the mould was in close contact with the infection’ (Wainwright 1989a). It took a month for the infection to clear, when the young patient was allowed to return to school. An investigation of this treatment by Wainwright in 1989 commented: ‘A hot-water, domestic starch (obtained from Boots, the Chemist) provided ideal, apparently selectively isolate species of Penicillium and Aspergillus. When a sample of starch contaminated with the former fungus was tested against Staphylococcus aureus on nutrient agar it formed a small inhibition zone, showing that it was producing an antibacterial agent.’

Ancient Antibiotics from Beer

Wooden model of beer making in ancient Egypt, located at the Rosicrucian Egyptian Museum in San Jose, California. (Courtesy E Michael Smith CC-bySA 3.0 Unported)

The ancients not only appreciated beerdrinking as a pleasurable convivial pastime, but the beverage was considered to have significant medicinal qualities. In Ancient Egypt it provided remedies that ranged from wound dressings and mouthwashes (to treat the gums), to enemas or a vaginal douche. The dried remains of the grain left over from the brewing process were even deployed as a fumigant (burned to produce smoke) to treat anal disorders (Armelagos 2000). Sycamore figs were often fermented in ‘sweet beer’ for treating intestinal distress, urine retention, or used as a cough remedy. Onion, which was considered an essential remedy for treating snake bite, was finely ground in beer, masticated and spat onto the injury site. Another emetic recipe for the same purpose included onion, natron and sweet

EARTH MEDICINE: A MINERAL PHARMACY

beer (or a suitable fermented liquid) (Nunn 1996). The naturally fermented beer contained antibiotic substances. In the 1980s bone samples from a Nubian mummy were shown to contain the antibiotic tetracycline – indicating constant exposure over the four months that it would take for the bone cells to develop. Subsequent investigation of human remains from Egypt (Roman period) and Jordan (2nd century BC – 4th century AD) gave similar results. The antibiotic, which would have been incorporated into the diet, appears to have been in the beer. It would have been naturally formed due to fortuitous contamination by a streptomycete fungus (probably genus Streptomyces), during the traditional brewing process. As part of this process, bread dough was ‘set out’ to naturally acquire an airborne yeast, then partially baked, which allowed the yeast within to continue growing. Finally, it was added to a broth of malted grain to undergo fermentation. Under the right conditions the beer would become a significant antibiotic resource.

Antibiotics: The Dirt on Microorganisms

Lister’s chemical cabinet. This chemistry set was said to have been used by Joseph Lister at Glasgow when he was in residence during 1860–69 as Professor of Surgery. During this time he pioneered the concept of antiseptic surgery using carbolic acid. The chemical set, which was acquired by Henry Wellcome when the Male Surgical Ward at the Royal Glasgow Infirmary was demolished in 1928, is now housed at The Wellcome Collections, Science Museum, London.

A Brief Look at Antibiotic Discovery

Although many types of yeast are suitable for baking and brewing purposes, Saccharomyces cerevisiae (pictured) is the main species that has been instrumental to these endeavours since ancient times. (Image courtesy Masur, Wikimedia Commons)

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Penicillium chrysogenum (formerly P. notatum) mould produces conidia (spore chains) from brush-shaped conidiophores. (Courtesy Crulina98, Wikimedia Commons, CC-by-SA 3.0 Unported)

The latter part of the 1800s saw science take a serious interest in penicillin-based moulds that

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were observed to possess effective antibacterial properties. In 1870 the fact that mould could inhibit bacteria in culture fluid was mentioned by Sir John Scott Burdon-Sanderson, a lecturer at St Mary’s Hospital in London. A few years later, in 1874–75, William Roberts and John Tyndall demonstrated antibacterial effects of a mould called Penicillium. In the late 1870s the French scientists Louis Pasteur and Jules François Joubert found anthrax bacilli were inhibited by mould exposure. A decade afterward, in 1887, the French scientist Garré reported similar findings. Importantly, Ernest Duchesne, at the Imperial School of Military Medical Service in Lyon, wrote a paper in 1897 on the fact that Penicillium glaucum (an imprecise identification of the time that was applied to a number of moulds) healed typhoid infection in guinea pigs. He was inspired by Arab stable boys’ use of mould-based applications for healing sores on horses’ legs. However, the article was largely ignored by the medical community. Other researchers in Belgium (Gratia & Dath 1920) and Costa Rica (Twight 1923) demonstrated that species of Penicillium, in particular, had antibiotic effects. Their work was similarly dismissed. A little later, in 1928, the Scottish biologist Alexander Fleming was to reveal the specific value of Penicillium notatum – although it was over a decade before he could convince any chemist to take the idea seriously enough to develop a stable form of the drug. The discovery was pure chance, as not all strains of this bacterium produce penicillin, and few produce it in any great quantity. It was a highly fortunate set of circumstances that resulted in the right mould, with a suitable form of substrate, and the right conditions for incubation, occurring together. It was even more fortunate that Fleming didn’t overlook the fact that one of his bacterial tests had not grown Staphylococcus bacteria. He proceeded to validate the mould’s antibacterial activity with the help of Ronald Hare. Later, the research skills of Howard Florey and his team, notably Ernest Chain and

Norman Heatley, were essential in bringing penicillin production into reality in 1938. It was enterprising research in the United States during 1941–44 that turned production into a viable commercial venture, initiating the supply of large quantities of pharmaceutical-grade material. It was a tortuous road to achieving the provision of effective antibacterial drugs for practical clinical use. Early attempts at producing penicillin employed old dairy equipment, and then hospital bedpans, for growing the mould. The collection process merely involved straining the liquid underneath the mould through parachute silk. Later, Florey went to the United States to search for better production methods, and a thick liquid by-product from corn milling was employed as a growth medium at the

Sir Howard Walter Florey, co-awarded the Nobel Prize for Medicine 1945. Penicillin, which is produced by Penicillium chrysogenum, was discovered by Alexander Fleming in 1929. Howard Florey, Ernst Chain and their team purified and concentrated the antibiotic – leading to extraordinary success in the treatment of infections during World War II. In 1945 Fleming, Florey and Chain shared the prestigious Nobel Prize for Medicine for their discoveries. (Image courtesy The Nobel Foundation, www.nobelprize.org)


National Center for Agricultural Utilization Research in Peoria, Illinois. This enabled ten times the amount of penicillin to be produced. Production was originally low at 4 units/ ml, with 40 units/ml being achieved with advances in the culture medium in the United Kingdom. Even so, it was more than a year before enough could be produced for clinical trials. Subsequently a strain was found that yielded 70–80 units/ml – a significant advance that led to further studies using X-rays and UV rays in the hope of inducing mutations with a higher yield. Success resulted with the production of a strain that produced 250 units/ ml. Later advances increased the yield to 900 units/ml, then 2500 units/ml. Industrialisation ultimately led to the discovery of higher yielding strains – and the development of deep-tank fermentation processes by scientists at Pfizer. Today descendants of Penicillium chrysogenum produce 50,000 units/ml (around 30 g) for drug production. In 1952 Austrian chemists at Biochemie (now Sandoz) developed the first acid-stable form of penicillin (Penicillin V) suitable for oral administration (Ligon 2004; TomVolkFungi.net; Fiechter & Beyeler 2000).

The search for high-yielding strains of Penicillium chrysogenum evaluated samples of moulds from an enormous variety of fruits, grains and vegetables. The search went far and wide and, during the Second World War, air force personnel were even encouraged to send samples of soil from across the world to the Peoria laboratories in the United States for analysis. Mary Hunt, the researcher who struck gold, gained the nickname ‘Mouldy Mary’ for her indefatigable searches. It was a mouldy Cantaloupe (Rockmelon, Cucumis melo) that was finally found to harbour the jackpot strain.

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Howard Florey featured on the $50 Australian banknote, 1973–1995.

Soil is a much more interesting topic than most people realise. Soil-based microbes have contributed to modern medicine on a vast scale, having a profound and lasting impact on human health. The unique properties of soil as a therapeutic agent lie in the role it has played in the discovery of antibiotics.2 It has been a remarkable resource for antibioticproducing bacteria, with around 50 per cent of the antibiotics that have been discovered produced by a single bacterial order, the Actinomycetales. One genus rates particular importance – Streptomyces (Abrahams 2002). The selection of ordinary soil as a candidate raw material for a drug production enterprise may appear unlikely. Yet this is exactly what happened in the 1940s when some innovative investigations tackled the concept of dirt possessing antibiotic activity. This led two independent researchers, botanists Paul Burckholder and Benjamin Duggar, to examine thousands of soil samples across the globe. Burckholder’s investigations at Yale University resulted in the discovery of Streptomyces venezuelae in a soil sample from Venezuela, from which chloromycetin (chloramphenicol) was isolated. This antibiotic was first used against an epidemic of typhus in Bolivia in 1947. The discovery was serendipitous, with some typhoid patients accidentally receiving injections of chloromycetin. They unexpectedly recovered – an event that was to herald the introduction of broad-spectrum antibiotics. Almost simultaneously, the hazards of inappropriate drug use were to become apparent. 2 Not all forms of earth have antibiotic properties, and it should be noted that ‘antibiotic’ is a specific term that refers to microorganisms that kill or inhibit the growth of other microorganisms.

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Stained Penicillium sample. Penicillium belongs to the famous Ascomycetes classification. There are around 300 species of these soil fungi, many of which are food spoilage moulds. A number are used as flavouring agents – for example, various Penicillium spp. are the moulds found in blue cheeses, while P. camemberti and P. roqueforti are used to make Camembert, Brie and Roquefort. There are, however, also numerous species that produce highly poisonous mycotoxins. (Image courtesy Peter Halasz)

The subsequent widespread and indiscriminate use of chloromycetin revealed the potential of the antibiotic to cause serious side-effects, notably blood disorders that included severe anaemia. Eventually the drug was replaced by penicillin, which was a safer alternative – although penicillin sensitivity was a serious side effect for some people. Even so, chloromycetin has remained of value for specific conditions, including the treatment of drug-resistant Staphylococcus bacteria. It continues to be employed in typhoid, salmonella and meningitis infections. Benjamin Duggar, a 71-year-old professor of botany, began his search for an antibiotic that would effectively treat tuberculosis, and was to discover another, quite different therapeutic agent. In the 1940s, at the University of Wisconsin, Duggar reviewed over 30,000 soil types to eventually unearth a vitally important antibiotic on his doorstep – which, strangely enough, was developed from microbes only found in a cemetery near the university (Stetter 1993). His work revealed the potential of Streptomyces aureofaciens, resulting in the subsequent development of aureomycin (chlortetracycline). Although ineffective in tuberculosis, it had a good broadspectrum activity similar to chloromycetin. Around the same time, in 1943, the

‘Penicillin cures Gonorrhoea’: educational poster from World War II. (Courtesy Kay Latimer, CDC, Public Health Image Library)

antitubercular antibiotic streptomycin was extracted from Streptomyces griseus by Selman Waksman – an actinomycete he had originally examined 28 years earlier when working on his doctorate. While useful for the treatment of tuberculosis, it was not as safe as penicillin for general use. A serious side-effect was the development of deafness due to nerve damage, therefore improvements in drug development continued to be imperative (Sneader 1989). Thereafter, in the late 1950s, a flurry of tetracycline drugs became commercially available.

Selman Waksman was a professor of biochemistry and microbiology at Rutgers University whose work led to the discovery of over twenty ‘antibiotics’, a term which he coined. In 1952 he was awarded the Nobel Prize for Physiology or Medicine in recognition of the discovery of streptomycin – ‘the first antibiotic active against tuberculosis’. Neomycin was another important antibiotic that originated from his work. (Image courtesy Library of Congress Prints and Photographs Division: New York World-Telegram and the Sun Newspaper Photograph Collection, taken by staff photographer Roger Higgins)


Their use was to cause unforeseen problems linked to serious imbalances of the normal bowel flora. There was also the evolution of bacterial strains resistant to tetracyclines. Inevitably their deployment declined, although today they continue to have a role in treating specific infections due to organisms such as rickettsia, mycoplasma, brucella, psittacosis and various chlamydial infections, including trachoma.

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indicator for faecal contamination studies and some strains have been responsible for food poisoning. Pathogenic fungi rate equal concern, particularly Aspergillus, which can cause serious lung infections in immunosuppressed individuals, notably those suffering from AIDS. Desert/Valley fever or Desert rheumatism (coccidioidomycosis), a flu-like illness associated with extreme fatigue, has been associated with archaeological excavations. This is due to dust contamination with the spores of Coccidioides immitis, a fungus that prefers hot, dry conditions. The condition has been associated with severe pneumonia and meningitis – and fatalities have occurred. In addition, a soil mycobacterium (Mycobacterium avium subsp. paratuberculosis) can be a cause of infection in dairy herds (Abrahams 2002).

Low-temperature electron micrograph of a cluster of rod-shaped Escherichia coli bacteria (family Enterobacteriaceae), magnified 10,000 times. (Image courtesy Erice Erbe, digital colourisation by Christopher Pooley, Agricultural Research Service, US Department of Agriculture, Image Gallery)

There are numerous pathogenic organisms present in soil. While most of us would be familiar with the risk of contracting tetanus (Clostridium tetani), soil can also contain spores responsible for gas gangrene (C. perfringens) and bacteria such as Pseudomonas aeruginosa. The latter is of concern as an antibioticresistant pathogen that has become prevalent in hospitals. Faecal material in soil has the potential to contaminate water supplies with bacteria (Escherichia coli, Leptospira), protozoal parasites (Cryptosporidium, Giardia), cyanobacteria and some viruses. Some of these pathogens, for example E. coli, can remain viable for several months3 (Bisi-Johnson 2010; Abrahams 2002). Indeed, this bacterium can be used as an 3 It should be noted that not all forms of E. coli are pathogenic – and that some strains have even been included in probiotic formulations.

Cultures of various fungi and bacteria including Penicillium and Aspergillus. Over 60 species of Aspergillus have pathogenic potential – often being involved in skin lesions, ear infection and ulceration. (Image courtesy Dr David Midgley)

The numerous antibiotics that were discovered from soil origins have had a remarkable influence on the provision of commercial drugs – with an enormous range of antimicrobial agents being developed (Sneader 1989): • Erythromycin, discovered in 1952 in the Philippines from Streptomyces erythreus, was found to have activity similar to penicillin. • Penicillium janczewskii was isolated from soil samples from sites in Dorset (UK) where Conifers would not grow. The bacterium was toxic to fungi essential for the trees’ growth. From these origins

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came griseofulvin, a drug that continues to be used for intractable fungal skin infections. • Streptomyces nodosus was found in soil samples from the Orinoco River in Venezuela. This was the origin of amphotericin, which continues to be one of the most important antibiotics available for treating systemic infections, particularly for cancer chemotherapy patients with a compromised immune system. It is very similar to nystatin, another soil-based antifungal antibiotic that, although suitable for external use, was found to be too toxic for internal use. • The rifamycins are a class of antibiotics discovered in the late 1950s from Streptomyces mediterranei. Nocardia mediterranea was later found to be a good source of rifamycin B. This was of particular interest because, although this chemical had a low level of antibacterial activity, it could oxidise to a more potent agent. These discoveries finally led to the development of a derivative with significant activity against tuberculosis. Equally impressive was the subsequent development of a range of anti-cancer drugs primarily isolated from species of Streptomyces. Unfortunately many of the drugs had serious side-effects that limited their practical value, although a couple of the most successful, such as doxorubicin (adriamycin), remain in clinical use. The following summary indicates the most influential discoveries (Oliver-Bever 1971; Sneader 1989): Actinomycin A from Actinomyces antibioticus • (1940). Actinomyces are ubiquitous soil organisms with features common to both bacteria and fungi. This was the first antibiotic isolated from an actinomycete, although it was far too toxic for clinical use. Actinomycin C (cactinomycin, an antibiotic • complex) was isolated from Streptomyces chrysomallus (1949). It could produce partial remissions in Hodgkin’s disease and avoid the premature rejection of organ grafts. • Actinomycin D (eventually named dactinomycin) was isolated from Streptomyces parvullus (1953) – a highly active compound that provided a chance of remission in a number of rare forms of cancer – e.g. choriocarcinoma (cancer of the placenta), and Wilms’ tumour (a rare kidney cancer), muscle

Cultivation of Nocardia and Streptomyces gram-positive bacterial colonies, showing two positive results (a clear halo around the colonies), and two negative growth patterns (an absence of this clear halo, with the deposition of a melaninlike pigment). Both genera are members of the order Actinomycetales. (Image courtesy Dr David Berd, CDC)

Slant cultures demonstrating variations in colony appearance between aerobic Actinomycetes spp. – white colonies (Actinomadura madurae), yellow colonies (Nocardia asteroides), and red colonies (Micromonospora spp.). (Image courtesy Dr David Berd, CDC)

tumours (rhabdomyosarcoma), bone cancer and Hodgkin’s disease. However there were numerous toxic side-effects that limited its use – although it continues to be incorporated into some combination anticancer treatments.


Other antibacterial and anticancer drugs of note include: • Rufocromomycin from Streptomyces rufocromogenes (1952). • Mitomycin from Streptomyces caespitosus (1956). • Bleomycins from Streptomyces verticillus (1962). • Rubidomycin (daunomycin) from Streptomyces coerulorubidus (1962) • Daunorubicin (daunomycin, rubidomycin or cerubidin) from Streptomyces peucetius (1962). • Adriamycin (doxorubicin) from Streptomyces peucetius (1967) was to become one of the most successful antitumour drugs ever discovered.

Native Streptomyces Antibiotics The presence of endophytes within plant tissue is relatively uncommon, and their detection, particularly those from the genus Streptomyces, is of significant interest as antibacterial agents.4 Investigations have discovered a couple of unique Streptomyces from Snakevine (Kennedia nigricans) and the Fern-leaved Grevillea (Grevillea pteridifolia). They have been a source of novel antibiotics – munumbicins and kakadumycins, respectively. Indeed, the Fernleaved Grevillea yielded ‘the most biologically active endophytic Streptomyces spp. on record’. In particular, kakadumycin A had a broad spectrum of antibiotic activity, especially against gram-positive bacteria, and impressive activity against the malaria parasite (Plasmodium falciparum) (Castillo 2003). Snakevine, which has been utilised by Aboriginal people as a remedy for open bleeding wounds, also had a reputation for preventing infection. Overall 39 different Actinomycetes endophytes (primarily Streptomyces species) have been isolated from different Snakevine plants sourced from the Northern Territory – and, although the majority of these did not have antibiotic properties, at least seven were of interest for further evaluation (Castillo 2006, 2005). Of these, munumbicins (actinomycin 4 The term ‘endophyte’ describes a symbiotic relationship of a microbe within a plant. This can refer to various microorganisms (including bacteria and fungi) that reside inside healthy tissue, without causing disease.

The Fern-leaved, Golden or Silky Grevillea (Grevillea pteridifolia) was first collected by Joseph Banks near the Endeavour River, Cooktown in northern Queensland. The species name is derived from Greek pteris, ‘fern-like’, referring to the foliage. The flowers are particularly nectar-rich and the tree has gained fame as an ornamental, being used to produce many of the popular Grevillea hybrids.

antibiotics) were isolated with highly active antibacterial activity, notably against multi-drug resistant Mycobacterium tuberculosis and grampositive bacteria, as well as antifungal activity against Pythium ultimum. Of particular interest was their activity against MRSA and against the malaria parasite (Plasmodium falciparum). Indeed, in comparison the conventional antimalarial chloroquine, some munumbicins showed significantly greater activity (Castillo 2006, 2002). With regard to Snakevine the authors of the research paper (Castillo 2006) concluded: ‘It seems evident that this one host plant, the snakevine, with its complex of streptomycetes, alone can act as a veritable pharmacy to

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native peoples using it as a source plant to treat open bleeding wounds. There seems to be an unlimited number of other bioactive Streptomyces spp. associated with this interesting native plant.’ Endophytic Streptomyces with antifungal properties have also been isolated from herbal medicine plants from the Malay Peninsula, notably Thottea grandiflora (Aristolochiaceae), Polyalthia spp. (Annonaceae), and Mapania sp. (Cyperaceae) (Zin 2007). The latter two genera are found in Australia, with four native Polyalthia species (P. australis, P. michaelii, P. nitidissima, P. patinata), and one species of Mapania (M. microcephala) from the northern tropics (coastal Queensland and Northern Territory) and Papua New Guinea. Doubtless there are other native species about which little is known, notably those from the rainforest and marine environments, that would also be good candidates for review.

Antibacterial Earth

The use of earth (which is classified as a geological nanomaterial) as a healing agent for skin infections is one of the ancient customs that fell into disfavour in modern medical practice. However, considering the origins of antibiotic therapy, it should be no surprise to find that research has been gradually substantiating this old practice. Specific clay minerals (notably iron-rich clay) may prove valuable in the treatment of bacterial diseases, including drug-resistant infections. Recently, African clay poultice treatments for Buruli ulcer infections due to Mycobacterium ulcerans were found to give excellent clinical results, with complete healing and minimal scarring.5 The condition is problematic to treat as it responds poorly to antibiotics in the ulcerative stage, and surgical intervention can result in significant disfigurement (de Courrsou 2002; Weir 2002). The explanation of the clay’s activity was discovered to be quite a complex affair. Two types of French Green clay (iron-rich smectite and illite) were involved in the treatment protocol, and they were eventually shown to have quite different properties. In an intricate piece of detective work, it was found that one type had a significant antibacterial effect6 – while the other had more potent healing properties. This was linked to their mineral composition. The clay type (CsAg02) possessed an extremely broad spectrum of antibacterial activity against Escherichia coli and ESBL (extended-spectrum β-lactamase E. coli), Salmonella enterica serovar. typhimurium, Pseudomonas aeruginosa, Mycobacterium smegmatis, M. marinum7, Staphylococcus aureus (as well as PRSA, penicillin-resistant, and MRSA, methicillin-resistant, S. aureus). However, while the second clay type had a similar 5 WHO figures estimate around 5,000 cases occur each year. However, this is likely to be an underestimate of the incidence of the condition which, in Africa (primarily Benin, Ghana, Côte d’Ivoire), is more prevalent in children 5–15 years old (Walsh 2011)

Snakevine, Kennedia nigricans (syn. Caulinia nigricans; Fabaceae). This is an attractive legume of Australia’s southern coast that ranges from New South Wales to the Northern Territory and Western Australia, as well as being found in Tasmania. (Image courtesy SatuSuro, Wikimedia Commons).

6 Because clay minerals are not produced by microorganisms they are not considered to be antibiotic in nature. They are classified as antibacterial – which means they can have bacteriostatic (inhibitory effect on microbial growth) or bactericidal activity (bacteria-killing activity). Antibacterial agents differ in their range of activity and, depending on the target bacteria involved, they have variable bacteriostatic or bactericidal effects. Broadspectrum agents are effective against a range of different bacteria (Williams & Haydel 2010). 7 M. marinum (which is related to M. ulcerans) can cause nodular and ulcerated skin lesions. It is often associated with exposure to contaminated water from aquariums, swimming pools and some marine environments – and includes marine animal stings or bites. The infection has the potential to be particularly problematic because it can invade into deeper muscle and bone tissue (Walsh 2011; Haydel 2008).


structure and chemistry (CsAr02)8 it was inactive (or even promoted bacterial growth) – showing that the antimicrobial activity was quite specific and influenced by the clay’s mineral composition. The conundrum was that the CsAr02 clay was found to actually promote experimental bacteria growth, particularly that of Escherichia coli (Williams & Haydel 2010; Haydel 2008). The causative bacterium of the Buruli ulcer, Mycobacterium ulcerans, has a complicated modus operandi. It utilises a necrotising (tissue-destructive) immune-suppressant mycolactone toxin that compromises the patient’s immune reaction. It was postulated that the smectite component of the CsAr02 clay could initially bind to the toxin, facilitating its removal when the poultices were first changed. This clay however, was only used for a short time at the beginning of the treatment, before switching to the CsAg02 antibacterial clay. This would have effectively sterilised the wound. A normal immune response could then proceed. It was possible that the clay allowed the normal bacteria to re-establish and thereby initiated a natural immune response. Afterwards healing could proceed naturally, with the associated skin granulation facilitating wound repair. Interestingly, the clay did not physically penetrate the bacterial cell. Thus it appears that the water in contact with the clay, and subsequent cation exchange, resulted in the creation of a chemical environment that stopped the pathogenic bacteria thriving9 (Williams & Haydel 2010; Williams 2008).

8 Both clays were primarily composed of iron-rich smectite and illite clay minerals. However, CsAg02 was enriched with magnesium and potassium, while CsAr02 was calcium-enriched. 9 Clay sourced from the Cascade Mountains, Oregon, USA, has shown similar activity.

A Matter of Transmission

The Australian Daintree or Bairnsdale ulcer, which is the same as the African Buruli ulcer, is a necrotising (‘flesh-eating’) form of mycobacterial infection with a characteristic ulcerative presentation. The condition appears to be increasing in incidence. Over 44 years (1964–2008), 94 cases were recorded across

Daintree River and mangrove lowlands.

the country, and were usually treated surgically – in some cases, the disease progression resulted in repeated surgery and skin grafting (Steffen 2009). Although reports during 2008–10 were low (and, possibly, the condition was underreported) with 18 cases, in 2011 a massive outbreak recorded 64 cases in Queensland (WHO Collaborating Centre for Mycobacterium ulcerans, Western Pacific Region, Victoria, Australia). The condition appears to be associated with an insect bite or minor trauma that does not heal, slowly progressing into an unsightly ulceration that is unresponsive to antibiotic treatment. Many Daintree locals believe that March flies are responsible for spreading the infection, although mosquitoes appear to be equally good candidates. A study of 14,889 mosquitoes captured during an outbreak of the disease at Port Lonsdale (south of Melbourne) showed that five different species could carry Mycobacterium ulcerans – possibly acquiring it through environmental exposure or acting as a vector reservoir (Lavender 2011; Wallace 2010; Johnson 2007). Certainly, there appears to be a correlation with areas associated with outbreaks of other mosquito-transmitted disorders such as Ross River fever and Barmah Forest virus (Johnson & Lavender 2009). To date, the issue of transmission remains unresolved. Different vectors may be involved in other environments. In Cameroon, the saliva of biting water bugs (7,407 samples) demonstrated the presence of Mycobacterium ulcerans – and it

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possum (Pseudocheirus peregrinus) and Common Brushtail possum (Trichosurus vulpecula) in areas where outbreaks of M. ulcerans infection have occurred – although the bacterium could not be cultured from these samples. Overall levels of infection or faecal contamination were 38 per cent and 24 per cent, respectively. In comparison, faecal contamination in possums from nearby uninfected sites was extremely low (less than 1%) (Fyfe 2010; van Zyl 2010). Certainly, it suggests that this bacterium has more problematic potential than initially appreciated – for wildlife, domesticated animals, and humans.

Blood-engorged mosquito. (Courtesy Gathany, CDC PHIL Library)

James

has been suggested that environment changes due to human activity could be facilitating transmission of the disease (Williamson 2012; Marion 2010). Moreover, there may well be a level of animal interaction resulting in an environmental reservoir for the disease. In Australia, Mycobacterium ulcerans infections have been recorded in horses, cats, dogs, native possums and koalas in areas where the infection is endemic (O’Brien 2011; Fyfe 2010; van Zyl 2010; Elsner 2008). In Victoria, high levels of mycobacterial (M. ulcerans) DNA has been detected in faeces from the Common Ringtail

Common Brushtail possum. (Courtesy Arthur Chapman, flickr)

Investigations of the iron-rich clay established that the mineral components buffered the pH of the solution and supported oxidation processes. Eventually conditions develop that result in increased iron solubility, creating an iron-saturated solution. Ultimately the iron was able to enter the bacterial cell and kill it (Williams 2011). Iron oxide (magnetite) has shown bactericidal activity against Staphylococcus aureus. It was also able to increase the growth of human bone cells, although the tissue-growth properties of clay remain unexplained (Williams 2011; Tran 2010). This is not the only method by which clays can exhibit antibacterial properties. There are a number of other soluble clay components are toxic to bacteria: • Allophane and imogolite-based clays have a chemical sorption process that deploys a number of bactericidal elements: copper, zinc, silver and cobalt (Williams 2011). Jordanian red earth from the Mediterranean • is a traditional treatment for skin infections and diaper rash. Soil samples, obtained from uncontaminated sites (i.e. away from industrial activity or urban settlements) demonstrated good

Iron oxide. (Courtesy Ben Mills, Public Domain, Wikimedia Commons)


antibacterial potential against Micrococcus luteus and Staphylococcus aureus. In this instance, the activity appears to be dependent upon a number of component antibiotic-producing bacteria – Actinomycetes, and strains of Bacillus and Lysobacter. The actinomycetes synthesised specific antibiotics (Actinomycins C and C2) upon pathogenic bacteria exposure (Falkinham 2009).

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Zeolites have rather extraordinary adsorptive10 and absorptive capacities and a high cation exchange capacity, with a useful affinity for oxidised silver ions. Silver-enhanced zeolite can thereby acquire broad-spectrum antibacterial properties against gram-negative and gram-positive bacteria, including Pseudomonas aeruginosa, Streptococcus aureus, S. mutans and S. sanguinis. This form of zeolite has particularly useful dental applications. Zinc oxide has also been utilised in dental composites for treating tooth caries and as a sealant. Vermiculite is another clay mineral that acquires antibacterial properties when loaded with copper ions – which has potential as an antifungal agent (Williams & Haydel 2010).

Sinkholes at Mineral Beach, Dead Sea, West Bank. Dead Sea ‘black mineral mud’ has shown antimicrobial (bacterial inhibitory and bactericidal) potential against Escherichia coli, Staphylococcus aureus, Propionibacterium acnes and Candida albicans. This hypersaline clay has been widely used for cosmetic purposes (Ma’or 2006). (Image courtesy Doron, Feldman)

Antibacterial Metals Metallic oxides (silver, copper, zinc, magnesium, calcium) have shown various levels of bacterial inhibitory and bactericidal properties. Silver-loaded clays have, however, gained centre stage as far as recent research is concerned. Silver-ion based preparations have been utilised as antibacterial agents for treating burn wound infections, osteomyelitis, urinary tract infections, and infections due to venous catheters (Williams & Haydel 2010).

Native copper, naturally-occurring copper that is devoid of impurities. (Courtesy Jonathan Zander)

Copper has a broad spectrum of antimicrobial activity – and an extremely long history of use. Malachite, a highly attractive green-coloured mineral composed of copper carbonate, is of particular interest as a cosmetic ingredient.11 Powdered 10 To adsorb something, or the process of adsorption, refers to a process that involves the attraction, binding and accumulation of particles on a solid surface in a condensed layer. Absorption differs in that a substance diffuses/penetrates into a liquid or solid. In the latter process a transition zone is formed adjacent to this substrate, and this new layer can have a different chemical composition (Williams & Haydel 2010).

Silver. (Courtesy Teravolt.org, Wikimedia Commons)

11 The mineral malachite should not be confused with the synthetic ‘Malachite green’ (triphenylmethane dye) – an antimicrobial dye that has been used for over 50 years in mycobacterial culture studies to inhibit the growth of contaminants. It is a useful indicator that changes colour in response to Mycobacterium tuberculosis growth and has therefore been used in the diagnosis of tuberculosis and in drug efficacy studies (Farnia 2008). ‘Malachite green’ is commonly used in the fish farming industry as an antifungal, antiparasitic and antibacterial agent. It has also shown effective anti-Candida activity (Dhamgaye 2012).

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aeruginosa. Malachite was also utilised as a wound dressing – Egyptian records mention its use for a burn that had become infected (‘foul’) and a breast wound (Nunn 1996).

Ancient copper ingot from Crete, showing animal skin pattern. Copper is a rather remarkable mineral that was used medicinally by the Ancient Egyptian, Greek and Roman cultures. It was the Romans who named the metal cyprium (now cuprum), ‘metal of Cyprus’, as it was mined on this island. The Greeks, who had copper mines on Crete, sprinkled copper oxide and copper sulphate powders on wounds to prevent infection. A decoction of red copper oxide and honey was similarly utilised. The use of copper as a storage vessel (e.g. for water) was also noted to prevent contamination (Dollwet & Sorenson 1985). (Image courtesy Chris 73, Wikimedia Commons CC-bySA 3.0 Unported)

The ancient Edwin Smith Papyrus, which is the world’s oldest surgical document (1600 BC), mentions the use of copper alloy filings from swords being dropped into chest wounds to sterilise them. The Ebers Papyrus (see picture page 193) notes the use of copper compounds for treating headaches, burn wounds, itching and neck ‘growths’ (which would have included boils). (Image from the Rare Book Room, New York Academy of Medicine, courtesy Jeff Dahl, Public Domain, Wikimedia Commons)

malachite has antibacterial properties that support its extensive use in Ancient Egypt. Experimentally malachite or its main component (cupric carbonate or hydroxide) has an inhibitory effect on diverse bacteria, including Staphylococcus aureus and Pseudomonas

Copper was discovered at Cobar, western New South Wales, in 1870 – with the Great Cobar Copper Mining Company Ltd being established in 1878. The open cut mine (pictured) has also been a source of zinc, lead, silver and gold. (Image courtesy Axel Strauss, Wikimedia Commons, CC-by-SA 3.0 Unported)

In the 1800s, during cholera epidemics in Paris (1832, 1849, 1852), copper workers were observed to have immunity to the disease, which suggested some sort of antibacterial effect. A few decades later, during the 1880s, copper arsenate was deployed in treatments for acute and chronic diarrhoea, dysentery and cholera. The pharmaceutical company Bayer developed an organic copper complex for tuberculosis – a remedy that was utilised until the discovery of antibiotics in the 1940s. Diverse copper preparations have also been effective for treating chronic adenitis (lymph gland inflammation), eczema, impetigo, scrofula, lupus, syphilis, anaemia, chorea and facial neuralgia (Dollwet & Sorensen 1985). A particularly interesting record from Suffolk was published in The Daily Express of 1943: ‘Mrs. Eva Wood[’s] … great-grandmother used to collect all the new copper pennies she could, old copper kettles, smear them with lard and leave them in a damp place. When the mould had formed she would scrape it off into little boxes and everyone for miles around came to her for the remedy for what ailed them’ (Wainwright 1989b). An intriguing strategy that may well have introduced a copper component into the antibacterial mould growth. Copper also has anti-inflammatory properties. In


Malachite has been sourced primarily from Russia (Ural Mountains), France, Africa (Zaire, Namibia), America (Arizona), Morocco, Brazil and Mexico. Australia also has a number of famous sites: Burra Burra (South Australia); Rum Jungle (Batchelor, Northern Territory); and the Sir Dominick Mine in the Flinders Ranges (South Australia). (Upper image courtesy Heather Rabbich, Cairns; image of Rum Jungle malachite below courtesy Rob Lavinsky at irocks.com)

1885 the French physician Luton reported the use of copper for treating arthritis, employing an ointment made from hog’s lard and 30 per cent neutral copper acetate. Later, in the 1940s, Finnish copper miners were noticed to be immune to the ravages of arthritis – an observation that led to a series of successful clinical trials utilising a mixture of copper chloride and sodium salicylate for treating rheumatic fever, rheumatoid arthritis, sciatica, neck and back disorders (Dollwet & Sorensen 1985). Recently, investigations of the use of copper-based preparations as a transdermal anti-inflammatory remedy have also shown good results (Hostynek 2009). Studies have established that copper not only has inhibitory effects on bacteria and fungi – the mineral also possesses antiviral properties and can inactivate polio and influenza viruses. Indeed, the antimicrobial effects of copper are of sufficient potency to attract serious interest in manufacturing antibacterial surfaces that can reduce microbial transmission – particularly for use in health care institutions, notably hospitals.

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In comparison, microbes were found to persist on stainless steel at a much higher rate, thereby increasing the risk of contamination. Operating theatres could certainly be made much safer if infection risks were significantly reduced by microbe-resistant surfaces and air-conditioning systems (Weaver 2010; Michels 2009, 2003; Noyce 2007; Barker 2004; Noyce & Keevil 2004; Keevil 2000; Chang & Tien 1969; Avakya & Rabotnova 1966; Colobert 1962). To gain some idea of the potency of copper, a study of the incubation of the influenza A virus is relevant. After 24 hours on stainless steel 500,000 influenza A virus particles remained infectious – while after only 6 hours on copper, merely 500 particles were active (Noyce 2007). The results regarding other highly problematic hospital pathogens such as MRSA (methicillin-resistant Staphylococcus aureus)12 and Clostridium difficile were similar. Copper surfaces completely inhibited the viability of the bacteria, while stainless steel had no effect. The implications are of great significance (Weaver 2008).

Magnified image (440x) of rolled and annealed brass. Copper is not a highly durable metal, thus copper alloys make a better choice of material for most purposes because they are more resistant to corrosion. Copper can be used to make tin (with bronze, although aluminium and silicon may be present), copper-nickel (with nickel), nickel silver (with nickel and zinc), leaded copper (with lead) – as well as being combined with precious metals such as silver and gold. Brass is a copperzinc alloy that was used to make many of the fittings in old houses, such as doorknobs. Interestingly, they would appear to have exerted an intrinsic antibacterial effect due to the copper component of the metal – a truly extraordinary revelation (Wilks 2005). (Image courtesy Strangerhahaha, Wikimedia Commons, Public Domain) 12 The development of drug-resistant bacteria occurred early in the history of antibiotic use. Reports initially surfaced in 1942, and a mere decade later a significant number of Staphylococcus infections fell into this category. The drug methicillin was discovered in 1960, although its use also became compromised by the subsequent development of MRSA – the infection that plagues hospitals and those with poor immunity. Thereafter, bacteria resistant to multiple antibacterial drugs became increasingly problematic. Vancomycin remained in use for some time until, again, resistant strains developed (Sternbach & Varon 1992).

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Minerals as Paint and Paste

Queen Nefertiti (ca. 1370 BC – ca. 1330 BC), bust in the Neues Museum, Berlin, illustrating the eye makeup traditions of Ancient Egypt. (Image courtesy Arkadiy Etumyan CC-by-SA 3.0 Unported)

The potential of minerals as antibacterial agents has inspired their use since ancient times. Indeed, the use of ochre to cover skin blemishes was practised in Ancient Egypt. It was among the tomb treasures of this land that the first evidence of cosmetics was discovered. The Ancient Greeks and Romans were equally fond of personal decoration – although, at times, a substantial amount of experimentation with toxic metals occurred. Perhaps one of the most noticeable uses of cosmetics in Egyptian traditions was that associated with the art of eye decoration, notably mascara. Eye disorders in this region were rife – conditions such as conjunctivitis, trachoma (due to Chlamydia trachomatis), corneal ulcers, cataracts and diverse other inflammatory eye disorders were prevalent. The black kohl (ground lead sulphide) and green eyeliner (powdered malachite) were not only utilised for decorative purposes – they

had significant antibacterial potential. Eye disorders were treated with numerous recipes, many of which included these two minerals with additives such as natron13 and fermented honey. Two types of earth were also used in many prescriptions (a common ochre and red ochre) – as were common herbs, including acacia, carob, celery and hemp (Nunn 1996; Manniche 1989). Kohl cosmetic tube inscribed with the cartouches of Amenhotep III and Queen Tiye. Unsurprisingly, concerns with regard to lead poisoning have surrounded the use of traditional kohl-based makeup and eyeliners. (Image courtesy Keith Schengili-Roberts, Creative Commons CC-by-SA-2.5)

Mascara (kil) and container (kiledan). (Courtesy Ako Mahmoodi, Kurdistan)

13 Natron was readily available in dry lake beds around Ancient Egypt. It is primarily a mixture of sodium carbonate (a form of soda ash), sodium bicarbonate (baking soda), with small amounts of sodium chloride (halite, salt) and sodium sulphate. Like normal salt, natron was utilised as a drying, preservative salt for foods such as fish and meat (Nunn 1996). Natron was widely employed as a household cleaning agent – and was integral to the embalming process. Interestingly, it was used for making a smokeless fuel with castor oil, a good light resource that allowed tomb painting works to proceed without unsightly smoke stains developing. It was also an essential component of the ‘Egyptian blue’ dye.


Traditionally, mascara or kohl was prepared from a dark grey form of lead ore (galena). Lead chlorides (laurionite and phosgenite), which were not naturally found in Ancient Egypt, were deliberately synthesised for use as fine powders for makeup and eye lotions. They were prepared from lead oxide powders (litharge) combined with rock salt (and possibly natron) in warm water. The Romans (1st century AD) were equally familiar with these compounds, their expertise originating from Egyptian traditions. Dioscorides provided a detailed description of the manufacture of these lead chlorides, which was a fairly delicate chemical process. He also mentioned their medicinal qualities: ‘[they] appear to be good medicine to be put in eyes, and for foul scars, and for faces wrinkled and full of spots’ (Tapsoba 2010). A recent investigation tends to suggest that these cosmetics had a valid therapeutic basis: ‘the eyes of Egyptians bearing the black makeup were presumably prone to immediately resist a sudden bacterial contamination with extreme efficiency through the spontaneous action of their own immune cells’. The study suggests that a stimulation of the innate activity of nitric oxide supported the immune system in resisting infection (Tapsoba 2010). The Egyptians utilised many forms and colours of makeup – and, as malachite demonstrates, some were highly effective antibacterials. However, there was a serious risk of lead poisoning which, doubtless, had an effect on those applying elaborate makeup over long periods of time. Indeed, even in the 1990s it was discovered that lead levels in some commercial eye makeup from Egypt and India could be over 90 per cent – although, fortunately, not all preparations were lead-based (Hardy 2004, 2002, 1998). Mascara today is usually an amorphous charcoal or carbon-based product. The use of lead in cosmetics is, in general, banned – although this does not preclude its use as an illegal adulterant (see also ‘Lead Poisoning’, page 231).

Lead ore (galena) with calcite crystals from Elmwood mine, Central Tennessee. (Courtesy Rob Lavinsky at irocks.com)

Hieroglyph for antimony. Antimony is a highly toxic lustrous silvery-grey metal. In ancient times it was widely used as an ingredient in kohl cosmetic preparations. (Image courtesy Wikipedia)

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Laurionite (above) and phosgenite (below). The phosgenite sample is on display at the Vale Inco Limited Gallery of Minerals, Royal Ontario Museum. (Upper image courtesy Rob Lavinsky at irocks.com; lower image CaptMondo CC-by-SA 3.0 Unported)

Stibnite (antimonite), which is the mineral source of antimony, has been mined in Australia since the 1800s. Indeed, a quote from the Proceedings, Royal Society of Queensland (Lindon 1887) commented: ‘The association of gold and stibnite is not common, but it occurs in New South Wales, Victoria, Brazil, Transylvania, and in the Kingdom of Siam’. (Image courtesy Rob Lavinsky, irocks.com)

Pharmacy preparation of Antimony, which was well known for its poisonous properties. (Image from Herberton Historical Village, Atherton Tablelands, north Queensland).


Earth as a Poison Antidote

Clay deposit from Estonia, estimated to be around 400,000 years old. (Courtesy Siim Stepp, sandatlas.org)

The subject of the medicinal value of earth lends itself to an examination of the ancient use of special clays as detoxicant and remedial agents. Indeed, Terra Sigillata (‘sealed earth’) has long been utilised as a woundhealing agent, poison antidote, gastrointestinal and febrifugal remedy. The Pharmacopeia Londinensis or, the New London Dispensatory, Translated into English by William Salmon (1678) describes the physical properties of Terra Sigillata and its medicinal reputation: Sealed Earth: There are several sorts of Sealed Earth … viz. that from Constantinople, which is an ash colour, and indeed the best of all Earths which are known to us: though that of Lemnos [Cyprus] which is red, is often used for the true. The best Earth is known 1. By the sticking to the tongue. 2. If cast into water it rises up in bubbles. Terra Sigillata is drying, binding, sudorific… and resisting Plague, Poyson, Putrefaction, and all kinds of Malignity and Venom. It is chiefly used against the Plague, malignant Fevers, Diarrhoea, Dysenteria and biting of venomous Beasts etc …

In 1579 a German translation of a Latin work on the subject by Bertholdus (1583) was made by Johann Wittich. The text provides a discussion on the detoxicant properties of Terra Sigillata at some length (cited in Dannenfeldt 1984): For poisons eaten, drunk, or obtained in any way, a full drachm of this earth (more or less, depending on the type of poison and the age and condition of the patient) should be taken in any appropriate distilled water. If the poison was newly received, vomiting would occur. If the

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earth is taken some time after being poisoned, the patient should lie in bed, well covered, and sweat out the poison. If distilled waters, like those of blessed thistle, devil’s bit, swallowwort, butterbur, angelica, or pimpernell are not available, the earth could be taken in white wine. The new sealed earth can be taken in like manner against the plague, especially by those already infected. For preservation from a plague threat, one takes half a drachm in the morning in wine, vinegar of marigolds, or in any other convenient distilled water. Berthold reported that in pestilential times he had successfully given immediately one drachm of Silesian earth in wine, or distilled water, vinegar, or both to persons who had experienced the first manifestations of the plague, like pains in the heart and head, or any ‘anguish, grudging, lothsomeness, guiddiness’, or other signs. The patient is sent to bed, well covered, to sweat out the poison. In a few hours, the poison is driven out without any external boil or swelling. If the remedy is delayed and the plague infects most of the blood, a sore or carbuncle appears. In such cases, the vein nearest the plague sore must be opened. When the evil humours have thus been qualified, the heart will drive the poison to the sore, which, when ripe, should be lanced by an expert surgeon. Care must be taken that a little of the earth, steeped in vinegar and cinnamon, is put in a plaster and laid on the heart. The plaster, it will be observed, draws out a great quantity of poison. One must also remember that after the medicinal earth has been administered, the patient must place a piece of toast wet with good vinegar to his nose to prevent regurgitation of the earth. If swallowed earth is vomited, the patient should be administered earth until it is retained … For headaches caused by great heat, heavy labour, or wind, sleeplessness caused by worry or a troubled mind, the spirit is restored if in the morning one takes a drachm of the earth with good brandy, or with water of betony, rosemary, marjoram, pennyroyal, or such like. For pains and trembling of the heart, the earth assuages the trouble if a drachm of it is taken with waters of balm, celandine, motherwort, bugloss, borage, or gilliflower, or drunk in good white wine. Also, for inflamed and running eyes, or bleariness, temper this earth with rosewater or water of plantain, eyebright, valerian, fennel, or similar distilled water, dip into this a black hen-feather, and let a drop fall into the eyes. Or dip a linen cloth in the water and lay it on the eyes. For wounds in the eye, see a doctor and then put sealed earth and eggwhite or a suitable water on a cloth and lay it on the eyes. For wounds of the head or testicles, a linen cloth dipped in rosewater treated with this earth should be laid on the wound to prevent any inflammation or other dangerous condition.

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Medicinal clay or loess (‘healing earth’ or Luvos Heilerde), which mainly consists of montmorillonite, from the German manufacturer Luvos. The clay is recommended to ease gastrointestinal distress such as diarrhoea and acidic stomach conditions (heartburn) and as a nutrient supplement, notably for calcium (Limpitlaw 2010). (Image courtesy Martin C Doege, Wikimedia Commons)

Despite such praise, the value of Terra Sigillata (notably that sourced from the Striga goldmine in Germany) as a poison antidote was a matter of contention. To substantiate the value of the remedy, experiments were undertaken. Wilhelm, Landgrave of Hesse in 1580, ordered his physicians to provide good evidence of efficacy. They tested a mercury toxin and three highly toxic plant products on a group of unfortunate dogs: • Mercury toxin: A red dog with a white ring about its neck was given mercury sublimate (mercury chloride) as well as the clay remedy. He lived, albeit suffering great bouts of vomiting. A yellow cur with a white breast was given the mercury only. He later died, suffering great distress. • Aconite: A little black hound with a white tail was the third subject which was given ‘by negligence’ aconite and the clay. He lived. The fourth subject was a brindled shaggy-haired dog with a white tail which was given only aconite. He suffered terribly but was later given the clay remedy – and recovered. • Oleander (Nerium): A fifth experiment with a black cur with a white neck involved the use of Oleander (a cardiotoxin) and clay. He also suffered badly but recovered. The brown cur with a white neck that received only Oleander, did not. • Dogbane (Apocynum) leaves and roots were given to a dog which died rather quickly.

Aconite (also known as Wolfsbane or Monkshood, Aconitum napellus) is one of a number of toxic herbs prized as ornamentals – in this case for its wonderful blue flowers. Joseph Maiden mentioned, ‘There is a large demand for the dried root for the preparation of aconite liniment and tincture. The root is very poisonous, and intending growers must be warned not to mistake it for horse-radish’ (Maiden 1892). Aconite root contains cardiotoxins and neurotoxins. Poisoning is characterised by gastrointestinal symptoms (nausea, vomiting, abdominal pain), cardiac distress (arrhythmia, chest pain, hypotension), and neurological impairment (muscle weakness, numbness, paraesthesia). The heart dysfunction may not respond to treatment, resulting in fatalities. However, the root has long been utilised in traditional medicine in Asia, India and China – although this relies on soaking and boiling processes that hydrolyse and detoxify the aconite alkaloids, the level of which is reduced by around 90 per cent (Chan 2009). (Uppper image courtesy Farmer Dodds, flickr)


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In 1581 another test involving mercury sublimate was ordered by Wolfgang, Earl Hohenlohe and Lord of Langenburg. A condemned robber named Wendel Thumblardt offered to take ‘the most deadly poison devised and this new earth’. He was given mercury sublimate in a conserve of roses, with Terra Sigillata mixed with old wine administered immediately afterward. Andrew Berthold recorded: ‘In the judgement of the court physician and the apothecary, the subject was extremely tormented. However, in the end, the medicine prevailed and overcame the poison. The man recovered and was released to his parents’ (quoted in Dannenfeldt 1984). Around the same time Cristantus of Croenburg initiated another study that involved two dogs who were given mercury sublimate, mixed with lard. Only the one that received the medicinal earth survived. The evidence was therefore quite unequivocal with regard to the use of Terra Sigillata as a protective agent against a number of serious, usually fatal, forms of poisoning. Interestingly enough, more recent studies of the use of charcoal and fuller’s earth have shown that both were effective adsorbents (binders) of mercury – with charcoal being effective at a lower dose (Oubagaranadin 2007)

Mercury ore (above), liquid mercury (above right) and cinnabarite (right) (or cinnabar) (HgS), a mercury-based ore. Cinnabar (mercuric sulphide) is the most common source of the mineral mercury. The pigment vermilion (an orange-scarlet colour) is cinnabar-derived – and quite toxic. Due to its low melting point, purified mercury can become liquid at room temperature. Oxidising acids such as concentrated sulphuric

and nitric acids, as well as aqua regia (a highly corrosive acid mixture of nitric and hydrochloric acids that can dissolve metals) have been used to prepare sulphate, nitrate and chloride salts (respectively). The mercuric chloride toxin used in the experiments on dogs mentioned by Wittich (Dannenfeldt 1984) was a white, highly toxic, soluble powdered form of mercury. The poisonous consequences of mining cinnabar were a familiar hazard that was recorded in Roman times – a task assigned to felons and slaves due to the poor life expectancy. (Image on left courtesy Rob Lavinsky, irocks.com; top, courtesy Bionerd, Wikimedia Commons, CC-by-SA 3.0 Unported; above, specimen in Staatliches Museum für Naturkunde Karlsruhe, Germany, courtesy H Zell, Wikipedia).

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Mercury for pharmacy use. Mercury was formerly prepared in many forms (oil, ointments and various combination products). Mercuric chloride, mercuric iodide and mercuric nitrate were among those utilised as an antiseptic, germicide and anti-syphilitic remedy. Despite the inherent risk of toxicity, these preparations were effective antimicrobials. Mercuric chloride had a particularly extensive reputation as a cathartic, healing agent (alterative), diuretic and antiseptic. It was recommended for all manner of diseases: gastrointestinal distress (nausea, vomiting, flatulence, constipation, dysentery), liver problems (hepatic congestion), as a purge in infectious diseases, and even as a diuretic in dropsy (fluid retention) due to heart problems (Merck Index 1940). (Image from Herberton Historical Village, Atherton Tablelands, north Queensland)

Clay for Enterotoxins Medicinal Charcoal

Charcoal and Activated Charcoal, from the British Pharmaceutical Codex, 1934. thighs. To heal the wounds, they used charcoal powder, and sometimes just wood ashes pounded down. The aborigines never laid up with their wounds, though one wonders at it. Father has seen in a fight the skin of the head cut right through to the skill with a waddy. These deep cuts on the head were treated in the same way as those on the body – just charcoal put in them, and the wound seemed to recover in a few weeks’ time. It would without doubt kill a white man to be treated in the same way.

Campfire charcoal.

Aboriginal people in Australia have long utilised charcoal as a healing agent. Tom Petrie’s Reminiscences of Early Queensland commented: They fought very fiercely, these men; some of the gashes were terrible. Father has seen dozens on their backs, and sometimes extra deep ones on their

Charcoal is reported to have a similar adsorptive effect to clay. Indeed, the detoxicant effect of charcoal has been familiar to medicine since ancient times – and activated charcoal continues to be utilised in modern medical practice. Some recent studies have even suggested that charcoal is more effective than kaolin at adsorbing (binding) endotoxins (Dominy 2004).


The ability of clay to act as a detoxicant in the gastrointestinal tract has shown interesting protective effects in a number of disease conditions. Recommendations for clay as an antidiarrhoeal agent has been one of the tenets associated with its use since ancient times. Wittich (1579) mentioned that: ‘The German sealed earth has the power to cure catarrh. One drinks in the evening and morning, or frequently, some of the earth in white wine or other liquid to perspire immediately and find relief. For ruptures, dysentery, or diarrhoea, in the morning and evening take a drachm of this earth with water of tormentil, of oak leaves, or of acacia flowers’ (quoted in Dannenfeldt 1984). The latter are three wellrespected astringent herbal remedies. The process involved appears to be multifaceted. The adsorptive activity of the clay not only acts to bind minerals and toxic compounds, but the clay itself has a direct protective effect on the gastric mucosa. It acts to increase mucus secretion, prevent mucus breakdown, and buffers gastrointestinal pH levels.14 By staying linked to the mucous layer the clay also acts as a physical barrier (Rowland 2002). This modifies the chance of gastrointestinal disturbance, helping to reduce symptoms such as nausea, vomiting and diarrhoea. Certainly, these effects would help to explain its use by pregnant women as an antacid, ‘stomach-settling’ remedy. Furthermore, the direct antidiarrhoeal effect of clay is supported by an antibacterial action involving the adsorption of the bacteria and their toxins, including intestinal enterotoxins. Indeed, there are a number of pharmaceutical products such as Kaopectate (which has kaolin as its main ingredient) that continue to use clay as an antidiarrhoeal ingredient. Metahalloysite, a kaolin derivative, has a similar reputation (Krishnamani & Mahaney 2000; Mahaney 2000; Johns & Duquette 1991a). 14 Additionally, processing by grinding the clay removes coarse particles and can increase its pH, thereby assisting in the digestion process. However, there is the drawback that toxic elements may be concurrently made more bioavailable for absorption by the body (Ekosse 2010).

Kaolin and Smectite The absorbent (water-absorbing) properties of mineral clays make them useful antidiarrhoeal agents because they eliminate excess water as well as gases. They have a direct protective effect

A kaolinite mineral mine in Bulgaria. Kaolinite (kaolin) is one of the most common minerals and is mined in numerous countries, notably Australia, Brazil, Bulgaria, the Czech Republic, France, the United Kingdom, Iran, Germany, India, Korea, the People’s Republic of China, and the United States. (Image courtesy Nikola Gruev, Wikimedia Commons, CC-by-SA 3.0 Unported)

on the bowel and can bind bacteria or viruses, thereby facilitating their elimination. Kaolinbased clay preparations (e.g. Kaopectate) can slow down intestinal transit times, providing the body with more time to absorb water and minerals, thereby solidifying the stools and preventing dehydration. Palygorskite (attapulgite) has a similar effect (see also Table 5.1) (Ekossi 2010; Carretero 2002; Maxwell 2000). Smectitic clays, which are richer in magnesium carbonate (MgCO3) than kaolin, have a natural detoxicant effect on the gastrointestinal tract as they can adsorb toxins (heavy metals, free radicals, pesticides). These clay types are useful for treating constipation, allergies, diarrhoea, indigestion and intestinal ulcers (Ekossi 2010). Recent studies found that dioctahedral smectite15 was clinically useful for diarrhoeal forms of irritable bowel syndrome (Chang 2007). However, smectites do not have a gastrointestinal protectant effect as they cannot survive the acid conditions of the stomach (pH 2) or even the far less acidic environment of the bowel (pH 6). Nonetheless, calcium smectite has occasionally been utilised as a laxative due to the astringent action of the calcium component. Sodium smectite may also act as a laxative by osmosis – the sodium acting to draw more water into the bowel, which in turn 15 Smecta (active component diosmectite) is a commercial product based on smectite clay that has has been utilised as an antidiarrhoeal for both humans and primates (monkeys).

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increases the volume of the faecal matter and stimulates the propulsive activity of the smooth muscle of the intestine (Carretero 2002).

Kaolin (kaolinite or attapulgite), pictured above, is an antidiarrhoeal and detoxicant remedy that is no longer used in antidiarrhoeal formulations in the United States. In 2002 Kaopectate (a kaolin and pectate formula) was reformulated with bismuth subsalicylate replacing the clay component due to concerns about high lead levels. However, the risk was not fully ascertained. Importantly, the amount of lead present in different clay samples, and its bioavailability, can vary significantly: ‘It appears that whatever lead was measured within a clay sample or within a medication like Kaopectate was assumed to be the amount of lead a person would be exposed to, which does not say anything about the true bioavailability of Pb [lead]’ (Limpitlaw 2010; see also ‘A Matter of Bioavailability’, page 272). The source of the clay would significantly influence the potential lead contamination level. The drawback of the new formulation is that bismuth subsalicylate is not recommended for children or animals. It can cause severe constipation in children, and cats cannot metabolise salicylates (Limpitlaw 2010). (Image USGS, Public Domain)

For many centuries clay was a regularly utilised as an antidiarrhoeal remedy for the armed forces. The unsanitary conditions of war and of soldiers’ camps have habitually been associated with serious outbreaks of diarrhoea. During Roman times the physician Galen carried clay ‘tablets’ with him when on campaign. Clay rations probably saved many troops from the ravages of conditions such as cholera, typhoid and the like. Indeed, during the Balkan war of 1910 the use of clay to mitigate cholera infections was reported to reduce the mortality figures from 60 per cent to a mere 3 per cent. Russian troops were given a 200 g glass vial of clay to keep in their packs as an emergency remedy during World War I. The rations of Russian and French soldiers during World War II also utilised mineral clay – with one enterprising French medical officer adding clay to custard as a preventative for the ‘trots’. Apparently, even in severe cases, the administration of a clay–water mixture can be highly effective. The records of a Dr Julius Stumpf tell how he used kaolinite with great success to save his mother (and numerous other patients) during an

Pharmacopoeal preparation of kaolin. (Courtesy The Apothecary, Cairns, Australia) Front page image of Death bringing cholera, from Le Petit Journal, 1 December 1912. (Bibliothèque Nationale de France)


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Asian cholera epidemic in 1901 – the symptoms of diarrhoea, vomiting and cramping abated within a few hours of taking the remedy (Limpitlaw 2010; Reinbacher 2003).

Vibrio cholera. (Courtesy CDC, Public Health Image Library)

Waterborne transmission of cholera was first recognised in Europe in the mid-nineteenth century by John Snow and others. This sketch, ‘Death’s Dispensary’, was drawn by George Pinwell in 1866, around the time John Snow published his definitive studies. Untreated river water was responsible for the contaminated water supplies of London – similar to most other major European capitals. (Image courtesy CDC)

The antimicrobial properties of clay can extend to various forms of fungi. Aspergillus flavus is a common mould that infects stored food products and is a contaminant of water-damaged sites. This is the mould that grows on carpets following flood incursions. Exposure has been associated with serious lung infections (aspergillosis), with the potential to spread to other body systems, including the brain. In addition, many strains of Aspergillus flavus can produce aflatoxin, a highly toxic hepatocarcinogen

that is a contaminant of grains (notably corn, millet), oil seeds (particularly peanuts, almonds, Brazil and pistachio nuts), and dried fruit. Research has shown that clay (notably bentonite) had significant binding properties against aflatoxin in farmed animals. Therefore, it is not surprising that the use of smectite as an animal feed additive has a good protective effect against aflatoxin exposure, limiting its bioavailability (Mulder 2008; Phillips 1999, 1995). Research has subsequently focused on determining which type of clay is most effective and its suitability for use in food products to reduce human aflatoxin exposure (Jaynes & Zartman 2011; Phillips 2008; Tenorio Arvide 2008; Jaynes 2007).

Aspergillus sp. (Courtesy Janice Haney Carr, CDC)

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Ancient Legacies: Calcium and

Limestone

Calcite seabed, showing oyster shell remnants embedded in calcium carbonate. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio).

Iron-stained calcite, with a reddish hue, perched atop an earlier generation of hematite-coated calcite. (Courtesy Rob Lavinksy, irocks.com) Milk of Magnesia and magnesium carbonate used as antacids. Early twentieth century, displayed at Herberton Historical Village, Queensland. (Courtesy Tony Young)

Calcite crystals inside a fossilised shell. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Ancient limestone deposit from southern Utah. The round grains are calcium carbonate ooids, small sedimentary grains that are formed on the sea floor. (Courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Many antacid formulations are based on calcium or magnesium carbonate. Limestone is primarily composed of the shells of molluscs (and other creatures) mixed within a fine calcite (CaCO3) cement. Shells and pearls are good calcite resources, as are corals. Limestone is also a very good calcium resource that is often added to pet foods. Other mineral antacids have been sourced from dolomite (CaMgCO3) and magnesite (MgCO3). Nahcolite and trona are other natural sources of sodium carbonate with antacid potential that result from sea-water evaporation – and are commonly utilised as a baking soda resource (NaHCO3). Epsomite (MgSO4) is the source of the laxative Epsom salts. Magnesium sulphate also has emetic attributes and has been utilised as a poison antidote. In addition, a combination of epsomite with gypsum (alabaster) is effective for the relief of gastrooesophageal reflux (heartburn) that is associated with duodenal ulceration (Limpitlaw 2010).


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what their dimensions might be, but some were of enormous proportions and must have been quite a big job to execute. They were works of art, and produced a fine effect, and I imagine will be preserved in the future as a memento of the Great War’ (from Edward Fenton, Great Diaries from Around the World, Day Books).

Dolomite (calcium magnesium carbonate) from Limestone Gorge, Northern Territory. Dolomite has been used in horticulture as a soil conditioner, to lower acidity and provide magnesium. It is also used in marine aquariums to help buffer pH changes. (Image courtesy Craig Nieminski, flickr)

The Fovant Badges are military crests that were carved into the chalk hillside of Wiltshire, England, during World War I. They are currently scheduled as Ancient Monuments, although there continue to be problems with the long term maintenance of the sites. Of the eight surviving badges the largest is the Australian crest (pictured, 51 x 32 m), alongside those of British compatriots. Unfortunately the map of Australia, along with a number of other badges on the hillside, has faded into obscurity. (Image courtesy Fovant Badges Society, www.fovantbadges.com). The words of a timber merchant, Henry Peerless, in 1916 summarise the scene: ‘On our right hand side, behind the camps, was a range of hills, and we were attracted by a series of regimental crests on the side of these hills, most beautifully executed in, I think, white chalk. They varied considerably in size, and it is difficult to judge at a distance

Chalk, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841. Chalk is usually sourced from calcium carbonate deposits – which are resistant to weathering and quite porous. This allows them to hold good groundwater supplies, as well as sometimes forming spectacular environmental features.

A Dietary Detoxicant?

Clay appears to have been deliberately utilised to safeguard against the potential toxicity of unfamiliar or suspect food items for millennia. At times, it has been employed as an accompaniment to ‘famine foods’ (wild roots, bark, old seeds), some of which were known to have toxic properties (Abrahams 2005; Rowland 2002). There are some interesting

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investigations that support the detoxicant potential of clay against various chemical compounds. Clay has shown a high adsorption rate for alkaloids of various types – quinolizidine (sparteine, lupanine), tropane (atropine) and quinoline (quinine) – which was comparable to that of coal and charcoal. There were, however, differences in the efficacy of the clay. Quinine and atropine (lipophilic alkaloids) were more efficiently adsorbed than the water-soluble alkaloid lupanine (Mahaney 2000). This suggests that there is potential for a drug interaction problem with the use of clay as an antidiarrhoeal remedy. Studies from the Republic of Congo indicated that clay had a significant adsorption effect on chloroquine (around 60%) – which suggests that the concurrent use of both substances may compromise drug bioavailability in antimalarial therapy (Tsakala 1990). In addition to quinine, kaolin can significantly reduce the bioavailability of tannin-based drugs, that is, Quebracho (from the bark of Schinopsis balansae) and tannic acid. The adsorption level was significant (around 30%) in models resembling human digestive processes in the stomach and small intestine. Calcium oxalate, the main form of calcium present in plants, can also be rendered insoluble in the presence of kaolin (a precipitation level of 30% calcium was demonstrated) – which may therefore limit calcium bioavailability in some foods16 (Dominy 2004). The use of clay for cooking purposes has been a traditional strategy for the detoxification of starchy tubers. The common potato (Solanum tuberosum) may contain variable levels of water-insoluble and heat-stable glycoalkaloids (notably solanine), which may not be detoxified during cooking. Some races of potato have much higher toxic potential that others (see Volume 3 for details). The use of clay to modify their toxicity is illustrated by the strategies of Native American tribes in the American southwest and nearby Mexico with regard to the tubers of Solanum jamesii and S. fendleri – which were similar to that utilised with acorn processing (see ‘Making Acorns Edible’. The consumption of clay with wild potatoes was specifically designed to eliminate bitterness 16 However, calcium oxalate can be an undesirable food component that is usually detoxified during cooking (heat exposure). This suggests that, under these circumstances, the use of clay may well be a useful detoxicant. Once again, it is a matter of bioavailability. Soluble and insoluble forms of calcium oxalate are discussed in detail in Volume 3.

Bulrush: Typha

Aboriginal people utilised rhizomes of the Bulrush or Cumbungi cooked in earth ovens – with an intriguing use of clay balls (cricket-ball sized) as ‘heat retainers’. The entire process, however, was noted to be extremely labourintensive. A hole was dug, which was filled with firewood and the clay balls placed on top. These were then cooked and removed (still hot) when the fire died down. The hole was relined with moistened grass, upon which the Typha rhizomes were placed, covered with more moist grass, and the baked clay balls replaced on top. The earth oven was sealed with a soil covering to allow the food within to cook. The resultant starchy vegetable resembled a cooked potato. Inadequately prepared rhizomes retained purgative and emetic properties, which provided a good reason for being so careful with the cooking procedure (Rowland 2002; Gott 1999).

Bulrush.


and thereby prevent stomach pain or vomiting. These types of side-effects are associated with glycoalkaloid overdose (Johns 1990, 1986). However, some clays appear to have a better detoxicant effect than others. Investigations of the effect of different clays on tomatine (a potato glycoalkaloid17) adsorption showed that kaolin clay was not as effective as bentonitebased clay, which had a substantial detoxicant effect. Interestingly, the Andean clay known as P’asa, in which smectite was predominant (mixed with some illite and quartz), showed a higher adsorptive capacity than either of these clays18 (Johns 1986).

Making Acorns Edible

Green acorn.

Mochica ceramic representation of the Potato, Larco Museum Collection, Lima, Peru. Eating specific types of clay with potatoes is an established practice in some cultures. The preparation of bitter potatoes in the Andes of South America involved dipping them in a thick slurry of clay before use. In the American southwest, where potatoes were eaten cooked and raw, the clay was added during cooking or taken with each mouthful of food. While alkaloids can be bound by clay, the degree of efficacy will not only depend on the digestive process, but the nature of the clay itself exerts a significant influence (Johns 1986). (Image courtesy Pattych, Wikimedia Commons, CC-by-SA 3.0 Unported) 17 Tomatine is present in numerous Solanaceae food plants, notably tomatoes. 18 Andean people clearly distinguish between clays that are edible and those used for practical purposes such as making pottery and preparing whitewash. They can name numerous different types of edible earth (kaolinite, illite, smectite) which show considerable variation in mineral composition. Other clay minerals with an outstanding ability to retain water are halloysite and montmorillonite (Rowland 2002).

Mortar holes ground into rock for leaching tannins out of acorns, at Lost Lake, California, near Friant. (Courtesy Wikimedia Commons, Public Domain)

The use of clay with food items as a detoxicant has been practised across the globe. In places as diverse as California and Sardinia, local people added clay to acorn meal – a strategy that removes the tannic acid (the levels of which can be quite high) by binding it to the

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clay particles. Investigations determined that tannic acid ingestion from cooked ‘acorn bread’ could be reduced substantially – as much as 77 per cent (48 mg/g acorn meal). There was not only a reduction in toxicity, the clay made the meal more palatable. Even so, the use of clay alone was unlikely to adsorb enough tannic acid to effectively deal with the toxic levels that would have been present.19 Prolonged heating would certainly contribute to the process of detoxification by enhancing a catalytic action of the clay. The interaction of tannic acid with iron or aluminium is another factor that contributes to the detoxification process. There are potential nutritional benefits for clay use, depending on the bioavailability of the mineral components. Acorn–clay combinations showed that calcium was bioavailable in Sardinian clay (2.1 mg/g, i.e. 37% total calcium) and Californian clay (0.71 mg/g). In African clay samples, calcium was generally less bioavailable, with the exception of one sample from Kenya. The situation with other minerals was similar, with different locations showing variable bioavailability for specific minerals (%RDA, recommended daily allowance, country): iron (100%, Zaire), manganese (100%, Kenya, Zambia), copper (15%, Kenya, Nigeria, Kenya), calcium (15%, Kenya), zinc (5–7.5%, all African clays sampled), magnesium (8–10%, Kenya) (Johns & Duquette 1991a, 1991b). Other studies have given similar results. Therefore, while clay minerals can be present at appreciable levels, their bioavailability will ultimately determine their dietary usefulness. Certainly, in times of nutritional deficiency, some clays could have value as a mineral supplement.

19 California clay showed 5.6–23.7 mg/g tannic acid sorption. Under optimal conditions 1 g of clay could therefore adsorb 23.7 mg tannic acid from 10 acorns. Sardinian adsorption (clay:acorn ratio 1:8) would be 13.5 mg (around 8% total tannic acid). In practical terms, sorption is affected by pH, ionic strength and competing adsorbents. During processing (cooking) and digestion the sorption level is likely to be less than the maximum level proposed (Johns & Duguette 1991a).

In the 1530s, during his travels in the southeast of the United States, the explorer Álvar Núñez Cabeza de Vaca observed that the fruit of the Mesquite tree (Prosopis juliflora) was eaten with soil by the Native Americans – a combination that was said to make the fruit sweet and palatable (Abrahams 2005). Mesquite is a leguminous tree, the pods of which have been utilised as a flour resource. However, ‘Mesquite’ can refer to a number of Prosopis species. These are drought-tolerant plants with an invasive habit and Prosopis pallida (pictured) has been listed as a Weed of National Significance in Australia. (Images courtesy Kim & Forest Starr, Hawaii)


Avian Geophagy

Young chimpanzees in the Jane Goodall Tchimpounga Sanctuary, Republic of Congo. Observations of the eating habits of chimpanzees in Uganda found that they ate clay just before or after eating the leaves of Trichilia rubescens. Although the reason for this behaviour remains open to debate, the leaves of this plant contain limonoids with effective antimalarial activity (Krief 2004, 2006). Investigations showed that the soil-eating habit enhanced the pharmacological effects of Trichilia during the digestive process – which suggests that the clay could promote the antimalarial properties of the herb. In addition, it is of interest to note that local healers have utilised the same type of kaolinite-based soil as an antidiarrhoeal agent, which was considered particularly useful for bloody diarrhoea. Phytolacca dodecandra fruit, which contains saponins, has been similarly eaten with a clay accompaniment by chimpanzees. Whether this has any bearing on the usefulness of the latter herb is the subject of further study (Klein 2008). (Image courtesy Delphine Bruyere, Wikimedia Commons, CC-by-SA 3.0 Unported)

Phytolacca dodecandra fruit. (Courtesy Stefan Gara)

The Green-winged or Red-and-green Macaw (Ara chloropterus) is one of the clay-eating bird species of Peru. (Courtesy Michael Gwyther-Jones, Wikimedia Commons, CC-by-SA 2.0)

The habit seen in some birds (parrots, macaws and parakeets) of eating certain types of clay first attracted scientific attention in 1999 when it was observed in 11 species from Papua New Guinea. The parrots tended to eat earth when their diet had a high content of unripe seeds and fruit – a situation that would increase the toxic component of their diet. The adsorptive effects of clay minerals were suggested as a means whereby they could reduce the risk of poisoning. Investigations tend to confirm this hypothesis. Brine shrimp were exposed to the seed toxins found in the parrots’ diet and the clay additive significantly reduced the toxic effects. In addition, investigations of alkaloid (quinidine) exposure in parrots showed significant reductions (blood levels reduced by 60%) when clay was added to the mixture (Abrahams 2005; Gilardi 1999).

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The clay chosen by the birds is specific. Smectite-based clay had the highest quininebinding potential, which was 25 times greater than that of micas or kaolinites – a difference in toxin binding capacity that could vary by up to 300 per cent20 (Gilardi 1999). Subsequent studies of clay ‘licks’ used by eight bird species in Peru showed that the fine-textured clay had a high cation exchange capacity, which would facilitate toxin binding – as well as having a beneficial gastrointestinal protective effect. Moreover, this clay appears to be an important sodium resource, a mineral that is normally only present in low levels in the local plant foods. Surprisingly, the sodium availability from the clay was 40 times higher than from average plant sources. The clay did not, however, appear to be as useful for other minerals (calcium, potassium, magnesium, manganese and copper) which were present at levels comparable to, or less than, those in the local plants. Even though iron levels in clay could be around twice that of the vegetation, around 10 per cent of the flora also had a substantial iron component. Plant resources contained about 100 times more potassium (Brightsmith 2008).

Blue-and-yellow Macaws, Scarlet Macaws, Mealy Amazons and Chestnut-fronted Macaws at the clay lick at Tambopata National Reserve, Peru. (Courtesy Brian Ralphs, Wikimedia Commons, CC-by-SA 2.0) 20 Experimentally, each gram of smectite-clay bound 20 g of quinine, with the best soil type binding 40 mg/g quinine. Amazonia parrots that were given 50 mg of quinidine (a less toxic alkaloid) and 2 g clay showed a reduction in quinidine absorption by 60 per cent (i.e. the soil adsorbed 15 mg/kg) (Gilardi 1999).

Young Rhesus Macaque (Macaca mulatta). An analysis of the soils from Kowloon, Hong Kong that were eaten by hybrid Macaques found they usually favoured fine-textured soils that were higher in iron and aluminium oxides. Magnesium levels could also be high (Bolton 1998). (Image courtesy Jack Hynes, flickr)

Neotropical fruit bats, Artibeus sp., in Tortuguero National Park, Costa Rica. Research into the reasons for fruit bats in the Amazon rainforest visiting mineral ‘licks’ has concluded that pregnant and/or lactating females did not visit these sites for mineral resources but used the clay minerals to ‘buffer the effects of secondary plant compounds that they ingest in large quantities during periods of high energy demand’. This greater dietary diversity increased the potential for exposure to toxic compounds – and it would appear that clay is being utilised as a detoxicant component of the diet (Voigt 2011). (Image courtesy Wikimedia Commons user Leyo, CC-by-SA)


Drug–Clay Interactions

Processed clay minerals. (Courtesy Volker Thies)

The presence of clay in the gastrointestinal tract can alter drug bioavailability. Clay can influence its liberation and stability – thereby affecting drug release, its absorption and, ultimately, its efficacy. The consequent alteration in blood levels can therefore influence a drug’s clinical value. This action occurs because clay minerals carrying a negative charge will absorb protons. Digoxin can be used to illustrate the point. This important cardiovascular drug is affected by hydrolysis, a process catalysed by acid in the presence of the clay mineral montmorillonite. In the stomach, the acid level (pH 2) allows digoxin to degrade by 20 per cent per hour – whereas in the presence of montmorillonite it will be completely degraded within the hour.21 Digoxin would therefore lose its therapeutic value because adequate blood levels are not maintained (Porubcan 1979). Anti-inflammatory drugs such as dexamethasone and hydrocortisone are similarly affected by the presence of clay minerals such as palygorskite and sepiolite. More rapid degradation can occur with palygorskite due to its iron content – which acts as a catalyst, making the drug reaction occur more quickly (Carretero 2002). The issue of clay minerals and their effect on drug absorption is an interesting topic that has only fairly recently been evaluated with a view to innovative developments in drug delivery systems. The use of clay as an excipient22 can be quite handy when a 21 Drugs are designed to be maintained at a therapeutic dose in the blood for a predetermined period of time. Those that tend to degrade in the presence of protons will do so more rapidly upon exposure to clay in the stomach. This can occur even if they have not been administered at the same time – and may well compromise the efficacy of the drug treatment.

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slow-release strategy is desirable. Early studies have shown that the excretion of amphetamine sulphate in the urine was significantly reduced when it was absorbed in montmorillonite. This allowed the drug to maintain therapeutic levels in the blood for a longer period (McGinity & Lach 1977). The antibiotic clindamycin, which can form a complex with the same mineral, is highly adsorbed by clay in the stomach. Upon encountering changes in pH in the intestine it is then slowly desorbed and released – permitting a prolonged effect (Porubcan 1978). It is this slow-release effect of clay minerals that has been most useful therapeutically. Palygorskite, the smectites, kaolinite and talc, can therefore be used as excipients to change the physical properties of the drug delivery process (see Table 5.1; also Aguzzi 2007 for further detailed information on innovative claybased drug-release strategies).

Montmorillonite, from Minerals in Your World project. (Courtesy US Geological Survey & Mineral Information Institute)

Clay minerals have been utilised for other drug release strategies – as lubricants in pill manufacture (i.e. talc), as water-retentive tablet disintegrants (e.g. smectites) that swell and release the active drug component, or as tablet dispersants (i.e. palygorskite) that liberate a drug on contact with stomach acid. They can also provide inert bases for cosmetics, and can act as emulsifying, gelling or thickening agents. All these properties make them very useful for pharmaceutical 22 Excipients are additives used in the drug formulation for a specific purpose, with the aim of maximising the drug delivery process. Excipients act via decreasing or increasing the dissolution rate, delaying drug release, improving drug targeting, preventing or reducing side-effects, improving taste, or increasing drug stability (Viseras 2010).

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Table 5.1 Summary of Clay Types Used in Pharmacy and Drug Delivery Systems

(Based on Lopez-Calindo 2007; additional information on drug interactions as cited) Clay is a generalist term referring to a very finegrained mineral material that acquires plastic qualities on combination with water and hardens upon drying. The term ‘clay minerals’, however, has a more specific mineralogical meaning, referring to part of a family (phyllosilicates) that contain hydrated aluminosilicates with considerable amounts of Mg, K, Ca, Na and Fe, with some less common ions (tin, manganese or lithium). While all clay mineral types can have a variable chemical composition (see Lopez-Galindo 2007), processing is undertaken to remove undesirable components such as asbestos (tremolite) and carbon from talc. Furthermore, the use of a clay mineral for a specific purpose not only depends on its chemical composition, but the type of structure (1:1 or 2:1 layer type) significantly influences the cation exchange capacity. Textural differences, even between minerals that are structurally and chemically identical, will also affect absorptive properties and rheological (flow) qualities (Lopez-Galindo 2007). It is important to note the following differences in terminology (Viseras 2010, 2007): Kaolin, from British Pharmaceutical Codex, 1934.

purposes. Clay minerals (notably kaolinite, talc and smectites) have a high absorbency capability, with an ability to adhere to grease, toxins, bacteria etc., making them useful for inflammatory and infective skin problems (acne, boils, ulceration). For example, talc and kaolinite can be used as skin protectants and adsorbents to carry antibiotic, analgesic or antihistamine agents which are released on skin contact. The use of clay components in water-resistant sunscreen formulations is similar. Sepiolite and smectites can combine with compounds that absorb UV light, thereby enhancing the protection factor of a formulation. Some combinations can retard its dissolution in salt water, allowing longer sunscreen protection (Carretero 2002). The multitudinous applications of clay minerals, in this respect, are formidable.

• Th e pharmaceutical name of the smectites (montmorillonite and saponite) is magnesium aluminium silicate in the USA or aluminium magnesium silicate (AMS) in Europe. Bentonite is a colloidal hydrated aluminium • silicate montmorillonite-based clay. • Talc is hydrated magnesium silicate, while kaolin is hydrated aluminium silicate. • Activated attapulgite is heat-treated magnesium aluminium silicate.


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Table 5.1 Summary of Clay Types Used in Pharmacy and Drug Delivery Systems Classification: Clay mineral Official product Kaolin group Kaolinite (most common, i.e. ‘white clay’); halloysite Official product: Kaolin is a purified, natural hydrated aluminium silicate of variable composition

Qualities Kaolinite: • White/greyish white; becomes darker and more plastic when moistened with water. • Characteristic earthy taste, clay-like odour when wet. • Low cation-exchange capacity. • Variable chemical and physical properties. • Relatively low specific surface area, but capable of adsorbing small molecular substances, protein, bacteria, viruses in the surface of particles that are easily removed.

Drug uses: potential side-effects and use in enhanced drug-delivery systems Reduce drug absorption: Kaolinite will affect amoxicillin, ampicillin, atropine, cimetidine, clindamycin, digoxin, phenytoin, quinidine, tetracycline (Lopez-Calindo 2007).

Drug-release systems: • Halloysite: used to retain mesalazine (antiinflammatory) for treatment of inflammatory bowel disease in slow-release system (Viseras 2010). • Halloysite: prolonged release rate for propranolol (antihypertensive) (Aguzzi 2007). • Halloysite with diltiazem (antihypertensive) plus polymer coating (incl. chitosan) to reduce dissolution rate (Aguzzi 2007). Talc Often utilised as a skin dusting agent or cosmetic Pure talc: additive that is suitable as a carrier for antibiotic, • Translucent, white/near-white. Official product: • Odourless, flaky habit and easily milled to analgesic or antihistamine agents (Carretero 2002). Talc is purified, powdered, become a bright white unctuous powder. selected natural hydrated • Mineral qualities vary with type of talc and the processing method can alter its effects, e.g. Drug delivery systems: magnesium silicate hiding powder, wettability. Hydrotalcite: used to prepare extended release • Mineral composition, which can vary formulations of anti-inflammatory agents significantly from site to site, can have enormous (ibuprofen, diclofenac) (Aguzzi 2007). influence on potential uses. • Very good absorption capacity for oil and grease. • Plastic, colloidal swelling clay composed of Adsorbent activity: Bentonite • smectite. Smectites adsorb to amphetamine sulphate, Smectite-based clay tetracycline, tolbutamide, warfarin sodium, (mainly montmorillonite, • High cation exchange capacity (this influences diazepam. drug retention capacity). also saponite); ‘green clay’ • Differences in origin or chemical composition • Smectites can retain large amounts of a drug can influence technical properties; however very (Lopez-Calindo 2007). Official product: Bentonite is a natural pure (>95% smectite) deposits are common. Controlled drug-release systems: clay containing a • Smectites feel greasy and soap-like, odourless, • Ibuprofen (anti-inflammatory) combined with high proportion of slightly earthy taste. montmorillonite to retard drug release. drug) with montmorillonite (a native • Great colour variation: white, yellow, pink, grey, • Donepezil (Alzheimer’s pale green. montmorillonite, saponite or laponite. hydrated aluminium • Commercial products: fine-grained powder; • Montmorillonite plus polylactic glycolic acid: silicate may also contain nanoparticles loaded with docetaxel (anticancer magnesium and iron) purified bentonite is colloidal montmorillonite drug) for prolonged release over 25 days and purified to remove grit and non-swellable ore enhanced uptake by cancer cells. Note: Fuller’s earth is a components. mixture of clays with a • Ability to form thixotropic gels with water, can • Montmorillonite combined with polyethylene high magnesium oxide absorb large quantities of water (12–15x volume glycol has been used for controlled release content. It is usually increase). of paracetamol: improved dissolution of drug from the smectite group • Bentonite magma: 50 g bentonite with 1000 g with slower drug diffusion. (notably montmorillonite), purified water. • Nicotine: use of magnesium aluminium although attapulgite may (MgAl) silicate to reduce drug evaporation and be present in some clay modulate drug release. varieties. • MgAl silicate with sodium alginate: used to prepare films for buccal release systems: improved adhesion properties in mouth allowing controlled drug release. • Propranolol (β-blocker) combined with MgAl silicate. • Montmorillonite plus chitosan also used for prolonged release and biomedical applications (Viseras 2010). • Montmorillonite–lidocaine (anaesthetic): extended duration of activity (Aguzzi 2007).

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Clay minerals: May influence bioavailability: • Fine white-coloured powders that are free from • Palygorskite: decrease bioavailability of any gritty quality. loperamide and riboflavin. • Odourless and tasteless. • Magnesium trisilicate (sepiolite): decrease Official product: • Variable water absorption: palygorskite 5–27%; bioavailability of mebeverine hydrochloride, Attapulgite: purified native sepiolite 17–34%. proguanil, norfloxacin, sucralfate, tetracycline; hydrated magnesium • Purity: natural sepiolite deposits can be very pure may also retard dissolution rate of folic acid or aluminium silicate (95%); palygorskite less so (75%). paracetamol (Lopez-Calindo 2007). (palygorskite) Sepiolite: magnesium Activated attapulgite: palygorskite heated to Absorption decreased: trisilicate (a blend of Si increase adsorptive capacity; a high heat-drying • Anti-diarrhoea mixtures containing attapulgite and Mg oxides) process removes water to enhance absorbent decreased promazine (antidepressant) qualities: micronised fibre lattices trap liquids to absorption. make high viscosity suspensions. • Sepiolite: controlled release of antifungal and antibacterial isothiocyanates for sanitary Magnesium trisilicate: pharmacopoeal requirements protection in kitchens and food preservation can differ (minimum requirement % w/w): United (Aguzzi 2007). States Pharmacopoeia (USP 2006) 20% MgO, 45% SiO; European Pharmacopoeia (EP 2002) 29% MgO, 65% SiO Fibrous clays Palygorskite (attapulgite) and sepiolite

Note: There is also a special hectorite clay (including a synthetic hectorite, sodium magnesium silicate) that is used for cosmetic purposes, as well as specially modified clays (modified bentonites and modified hectorites) (see Viseras 2010, 2007 for details).

Petrified Forest National Park, Arizona, showing bands of pastel colours in the Blue Mesa. The bands indicate environmental conditions at the time the sediment was deposited. Blues and greys originate from carbon decaying in organic material that remained unexposed to air (buried or under water). Reds result from hematite (an iron-based material) – on exposure to air, even a small amount of iron can cause the rocks to oxidise (rust). The whites represent nearly pure bentonite clay. Ground water, percolating through the buried sediments, has also contributed to some colour changes. (Image courtesy Ritchie Diesterheft, flickr. com/photos/puroticorico)

Talc. (Courtesy Eurico Zimbres CC-by-SA 2.0)

Gypsum and Alabaster

In Chinese medicine gypsum is known as Shi Gao (‘stone paste’). The Reverend BE Read (1928) noted: ‘As bought in the drug shops it is in powder, which when moistened and then allowed to dry forms a hard mass’. It has been traditionally valued for treating feverish and full-heat conditions, with symptoms of high fever (without chills), irritability, thirst, profuse sweating – as well as lung disorders (cough and wheezing), stomach distress (swollen, painful


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Gypsum sand. White Sands National Monument, New Mexico. Gypsum (calcium sulphate dihydrate) is a very soft form of calcium from which alabaster items were carved in Ancient Egypt. (Image courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

Ancient Egyptian alabaster jar, Cairo Museum.

Selenite gypsum, from Minerals in Your World project. (Courtesy US Geological Survey & Mineral Information Institute)

Contaminant Considerations

There are a couple of contamination issues with regard to soil that require consideration. In particular the contamination of clay with domestic waste or toxic minerals has the potential for serious health consequences. In the past, children have suffered lead poisoning due to eating foreign objects (dirt, plaster, newspaper etc.) (Halsted 1968). Recently, in the United Kingdom, samples of the geophagic material known as ‘Calabash chalk’, popular in West African and Nigerian immigrant communities, were found to contain dangerous levels of lead, particularly for pregnant women who traditionally

with headache), toothache and heat-type skin problems (eczema, burns, ulcerated sores) (Bensky & Gamble 1986). In Australia mention was also made in 1908 ‘of the medicinal employment of earth, ashes, and sand; women rub their breasts with a pap made of gypsum for the purpose of causing a secretion of milk’ (E Eylmann, Die Eingeborenen der Kolonie Sudaustralien, 1908, p. 448, quoted in Laufer 1930).

utilised it as a remedy during pregnancy, probably to ease gastrointestinal discomfort. Its importation was subsequently banned (Abrahams 2006). There is a risk of increased exposure to cadmium and arsenic with some soils, notably those from Bangladesh where arsenic contamination of the groundwater supplies is a serious issue. Studies have found that these compounds could be present in a bioavailable form. The fact that high concentrations of cadmium have been found in the breast milk of women in Bangladesh suggests serious environmental contamination issues with regard to food supplies (vegetables and rice) that could be compounded by

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the habit of sikor (clay) ingestion. Indeed, merely 50 g of clay could raise the levels of arsenic and lead by 3and 6-fold, respectively, over the maximum tolerable daily intake – a significant cause for concern (AlRmalli 2010). Chronic low-level arsenic exposure, which also resembles lead poisoning, can be difficult to diagnose. The symptoms can be mild and insidious, with progressive disability developing in just about every system in the body: chronic fatigue with anaemia, gastrointestinal discomfort, liver dysfunction, neurological problems (polyneuritis), immune system dysfunction, hair loss, nails falling out, and a characteristic skin condition (hyperpigmentation, eczema) developing. Acute poisoning is associated with severe gastrointestinal distress, dizziness, delirium, coma, and often convulsions. This can result in circulatory collapse, renal and hepatic failure, and blood disorders. High levels of arsenic have been linked to an increased incidence of cancer (particularly skin melanoma), heart disease, stroke, chronic respiratory disorders and diabetes.

Arsenic: A Ubiquitous Toxin

red arsenic sulphide mineral, will impart a pink hue. Orpiment is another, gold-orange, arsenicbased mineral that is associated with volcanic activity and hot springs. It has been estimated that over 137 million people, in 70 countries, may be affected by arsenic poisoning – which is commonly encountered as a groundwater contaminant. The type of arsenic is important. The arsenic oxides, which readily dissolve in water, have particularly high toxic potential. Indeed, arsenic trioxide, which is 500 times more toxic than pure arsenic, may be naturally present in groundwater. Arsenic oxides (arsenites) are also a common by-product of ore processing. Landscapes with a long history of mining and smelting can have high residual soil levels of arsenic, copper, fluorine and lead – which can enter the food chain via livestock feed, or as a contaminant of crops. Arsenic poisoning has occasionally been linked to home-grown vegetables on land reclaimed from former mine dumps in the southwest of England. However, individuals exposed to low levels for a long period of time appear to develop a measure of tolerance to arsenic. Interestingly, soil iron has a protective effect as it can lower the bioavailability of arsenic to vegetable crops (Abrahams 2002). Another ubiquitous source of environmental contamination has resulted from the continued use of arsenates in the production of chromated copper arsenate (CCA) for timber treatments, arsenic-based pesticides, glass production, pharmaceuticals and non-ferrous alloys.

Arsenolite, from White Caps Mine, Nevada, USA. (Courtesy Rob Lavinsky, irocks.com)

The term arsenate (AsO4) refers to any compound that contains the arsenic ion – and many minerals fall into this classification. Arsenolite and claudetite are the main arsenic (arsenite)-based minerals that are formed from oxidation of arsenic sulphides. They are white in colour, although this may change if impurities are present – for example, realgar, an orange-

CCA-treated timber.


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Lead Poisoning

Garlic can have a significant detoxicant effect on arsenic. Preliminary investigations have shown that an aqueous (water) extract of garlic had a strong antioxidant and chelating efficacy, and/or oxidising capability that acted to reduce the toxicity of arsenic by altering trivalent arsenic into a pentavalent form (Chowdhury 2008). Thus the regular use of garlic in the diet could well have anti-toxin benefits that have hitherto remained unappreciated.

Lead ingots from Roman Britain, on display at the Wells and Mendip Museum. (Courtesy Rod Ward) Lead pipe in Roman bath in Bath, Somerset, England. (Courtesy Stan Zurek, CC-by-SA 3.0 Wikimedia Commons)

Solution of Subacetate of Lead or Goulard’s Extract (solution of diacetate of lead) consisted of acetic acid:protoxide of lead (1:2). This was primarily utilised, in a highly diluted form, for inflammatory skin disorders and fungal nail infections. Albeit rarely taken internally, there were some rather disturbing recommendations (for toxicological reasons) that mentioned its use as an enema for rectal discharges (including dysentery and cholera), and topically for leucorrhoea (vaginal discharge) and gonorrhoea. It was also employed as local irrigation for ENT (ear, nose and throat) disorders, as a mouthwash and gargle (Wood 1867). (Image from Herberton Historical Village, Atherton Tablelands, north Queensland) Iron can be an effluent contaminant of water supplies. This image shows acid drainage from surface coal mining, with iron hydroxide precipitate staining the water orange. (Image courtesy D. Hardesty, USGS, Columbia Environmental Research Center)

The presence of lead as a toxic contaminant of earth warrants particular attention due to the significant health repercussions, particularly for children in urban or industrial areas.

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In some places the soil is lead-rich due to the natural weathering of mineral deposits, whereas in other areas old mine workings are responsible. Leaded petrol and paint have left a remarkable level of residual contamination in the environment, particularly in urban soils (gardens, school playgrounds, parks) – which can contain numerous other compounds at toxic levels, including cadmium and zinc. The lead at these sites may even be more hazardous than that normally found in mineral deposits (pyromorphite) due to increased solubility (i.e. chloride- or bromide-based forms of lead). Even small amounts of lead exposure have been associated with behavioural problems, poor growth and development, and impairment of intelligence (Abrahams 2006, 2005). Lead poisoning has resulted from a geophagic habit (eating earth or clay). In one case where garden soil was involved, the clinical picture showed anaemia and seizures, which improved with chelation therapy. However, a resumption of the habit exacerbated the kidney failure (lead nephropathy) that had already occurred (Wedeen 1978). Other symptoms of lead poisoning in adults include hypertension and peripheral neuropathy (Hardy 2002). Children are more sensitive to lead exposure. Adults absorb 5–15 per cent of ingested lead, retaining only about 5 per cent of the amount absorbed. However, the bioavailability for children is much higher: they can absorb up 41 per cent of ingested lead, with 90 per cent of this being bound to haemoglobin in red blood cells. This is redistributed to soft tissues and is ultimately deposited in bone – with a half-life of over 20 years, resulting in hazardous long-term exposure. During pregnancy lead can be mobilised from the mother’s bone – and can cross the placenta and cord blood. Lactation is another problematic route of exposure. Infants and children are at particular risk of neurological toxicity and damage to brain function23 (Hardy 2002, 1998). Recently, studies have suggested a strong association between the prevalence of leaded petrol in the environment and violent crime. This rather frightening scenario may well find links between other forms of lead exposure and serious behavioural

The brain is the most sensitive part of the body with regard to lead exposure. This image shows brain damage (red and yellow clusters) due to childhood lead exposure: midline of left and right hemispheres (row 1); back and front of the cerebrum (row 2); lateral right and left hemispheres (row 3): below and above the cerebrum (row 4). (Image courtesy KM Cecil 2008)

problems in children. In Australia concerns have been expressed with regard to lead contamination of water from old pipes, living near mines or smelters, and occupational exposure (electronic equipment and plastics manufacture, battery recycling, glazes for pottery, jewellery making, alloys and 23 The traditional use of kohl as a sealant on the umbilical cord of the newborn is a significant risk factor in Egypt. The use of leadcontaminated kohl makeup has been identified in some Arabian Gulf and northern African countries as equally problematic (particularly for schoolgirls) as it is very bioavailable through the conjunctiva of the eye. Lead may also be a contaminant of traditional medicines (Hardy 2004, 2002).


casting work, renovation jobs). Hand to mouth (particularly sucking dirty fingers) has been the major means of contact for many children, and occupational exposure can be quite high in adults. The risk of exposure should not be underestimated. There are many avenues of entry into the home from lead-contaminated environments – dust on and inside cars, clothing, mobile phones, bags etc. Personal hygiene is extremely important – that is, washing the hair and nails before touching infants or children – and clothing should be washed separately from any unexposed materials. Blood levels should be below 10 mcg per decilitre, whereas high exposure can result in levels of 70–100 mcg/ decilitre.24

Blood film showing anaemia due to lead poisoning in cells on the far left and right (blue/purple dotting) and centrally (faded purple with irregular cell edges). (From Herbert L Fred & Hendrik van Dijk, Images of Memorable Cases – 50 years at the Bedside, Rice University Press, Houston, TX, 2007)

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pelvic area, upper and lower extremities). In 1968 in Toyama Prefecture, Japan, an outbreak was linked to cadmium-contaminated rice as the primary cause, although drinking water supplies were also suspect. The source of the problem was traced to the Kamioka Mine releasing cadmium waste into river water that was used to irrigate rice paddies. As rice is a staple part of the diet, exposure levels could be quite high. In addition, malnutrition appears to have contributedto the severity of the condition (Abrahams 2002). Recent investigations reviewed in the USA Consumer Reports have shown many rice products

Soil acidification will enhance the uptake of cadmium by vegetables such as lettuce and cabbage grown on contaminated sites.

24 See www.nhmrc.gov.au/guidelines/publications/gp2-gp3.

Excessive cadmium levels are an equally problematic matter of concern in many urban and agricultural environments. Cadmium can be a contaminant of sewage sludge, phosphate-based fertilisers and industrial emissions. In the 1960s, cadmium exposure was linked to the occurrence of a devastating form of osteomalacia (significant bone softening, with associated skeletal degeneration) and severe kidney damage. Known by the Japanese name of itai-itai (‘ouch-ouch’, referring to the painful nature of the condition), it primarily affected women, who experienced severe joint and bone pain (breast,

Terraced rice paddies. Soils with even relatively low cadmium concentrations can be problematic. The cadmium is made bioavailable due to acidic character of the soil (pH 5.1) – as well as low carbonate and low hydrous oxide soil components, particularly in rice paddies. The bioavailability of soluble cadmium was found to be around 4 per cent in rice paddies. In comparison, in high-cadmium soils at Shipham in the United Kingdom the level was 0.04 per cent. The latter was characterised by free-draining soils with a higher sorption capacity: high pH 7.5–7.8,and high CaCO, and high hydrous oxide levels (Abrahams 2002). .

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contain significant arsenic levels, particularly rice cereals and brown rice – as well as apple and grape juices. The implications could be quite worrying for children’s snacks and baby foods (Consumer Reports Magazine February & November 2012) – although there does not appear to be any current evidence of contamination with regard to Australian-grown products (http://www.consumerreports.org/cro/ magazine/2012/11/arsenic-in-your-food/index.htm). Other soil-based minerals with toxic potential include silver, beryllium and mercury, and various radioactive isotopes. Indeed, white clay (kaolinite) and green clay (bentonite) can contain levels of radionuclides that would advise caution in their ingestion. The level in green clay tends to be higher, and suggestions have been made that merely ingesting 1 g per day can represent 6–10 per cent of the annual allowable dose, which is 1 millisievert (mSv) (Silva 2011). Inhaled radon is another radioactive material with detrimental potential for human health. This gaseous breakdown product of radioactive minerals (uranium, thorium) can diffuse through rock and soil to escape into the atmosphere. Unfortunately, radon has been found as a contaminant in urban households in areas where naturally high ground levels of radioactive compounds occur. This gas can be drawn from the earth due to a pressure difference between the house and the soil underneath, resulting in unexpectedly high levels in urban settings. Radon

Radon test kit. Radon is not the only natural product with a gaseous character that can give rise to environmental concerns. Wetlands have the potential to be a problematic source of methyl halides (CH3Br, CH3Cl). Even more concerning is the fact that the pesticide CH3Br (methyl bromide), which has been manufactured for widespread use as a soil fumigant gas, is easily released back into the atmosphere. It is now listed among the most important causes of ozone destruction, rating just below CFCs and halons (Abrahams 2002). (Image courtesy US Government, NIH)

exposure is an important contributing factor to lung cancer and myeloid leukaemia, as well as other cancers. Contamination occurs not by the action of radon itself – but because its breakdown products (polonium isotopes) adhere to dust particles, which are then inhaled (Abrahams 2002).

Toxic pesticide warning sign. (Courtesy Colin Grey, Wikimedia Commons, CC-by-SA 3.0 Unported)

Crop dusting: biplane spraying pesticide in 1947. Despite the fact that the spray was dispersed from the rear of the plane, pesticide exposure was still a risk for the pilot – not to mention those on the ground. There was not only the problem of potential exposure to the toxin during spraying. Quite high levels of exposure could easily occur during its formulation – and later, when cleaning the spray tanks. (Photograph by Dick Robbins, courtesy US Centers for Disease Control, National Institute for Occupational Safety and Health)


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Various other minerals of interest are usually only found as trace elements, although in excess their presence can be problematic. In addition to iron and zinc, they include chromium, cobalt, copper, fluorine, iodine, manganese, molybdenum and selenium. (Soils that are deficient in fluorine, iron, iodine and selenium have also been associated with serious health problems.) • Molybdenum: poorly drained soils with a neutral/ alkaline character can result in an increased intake. Very high levels appear to be associated with a prevalence of gout in Armenia. Exposure (high levels) may also reduce the incidence of dental caries – although a dietary deficiency from staple crops (maize, beans, pumpkins) in South Africa has been linked to a high incidence of oesophageal cancer. • Iodine: soils that are deficient in this element are relatively common across the globe.25 A high pH and a high organic matter component tend to reduce iodine availability, retaining it in a non-bioavailable form. Goitre (enlargement of the thyroid gland) is the most prevalent symptom of deficiency, although there can be numerous associated problems: stillbirth, abortion, congenital abnormalities, endemic cretinism (mental deficiency, deaf-mutism,

Some dietary components (goitrogens) can block the utilisation of iodine, resulting in the development of goitre. Thiocyanate release from inadequately prepared cassava (pictured) can act as a goitrogen.

spastic diplegia), diverse neurological disorders and impaired mental function. • Selenium: A deficiency of soil selenium in locally grown cereal and vegetable crops can result in low dietary levels. Significant reductions in selenium bioavailability, even in high-selenium soils, occur when the soil has a high pH (<7.6) and high organic matter content. Selenium deficiency has been linked to the development of Kashin-Beck disease (osteoarthropathy with joint deformity) and Keshan disease26, which are prevalent in some parts of China. The latter is a degenerative form of cardiomyopathy (moderate to severe heart enlargement) resulting in heart failure and death. High selenium levels, which can be equally problematic, have been associated with hair and nail loss, skin lesions, neurological disorders and mottled teeth. • Fluorine: chronic exposure to high fluorine levels and the fluoridation of drinking water, as well as food sources (acidic soils can enhance the uptake of crops), can result in a condition known as fluorosis. This results in skeletal and dental bone 25 WHO statistics from 1996 estimate that 29 per cent of the world’s population is at risk of iodine deficiency: 656 million people have goitre, and 43 million have some degree of mental defect (including 11.2 million suffering cretinism) (Abrahams 2002). While recent figures have shown an improvement, with a reduction in the number of countries, it is still ‘estimated that 31.5 per cent of school-age children (266 million) have insufficient iodine intake. In the general population, 2 billion people have insufficient iodine intake. The number of countries where iodine deficiency is a public health problem is 47’ (de Benoist 2008).

Iodine crystals. (Image Wikipedia, Public Domain)

26 For both conditions other factors may have a contributing role in their aetiology – for example, virus exposure, low vitamin E or molybdenum intake has been linked to Keshan disease. Fusarium contamination of grain supplies and humic acid in drinking water may be associated with KashinBeck disease (Abrahams 2002).

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destruction that can become crippling.27 Tea, in particular, concentrates fluorine in its leaves, with substantial amounts being released during the infusion process. Fluorosis can also result from air pollution, notably from burning coal. For instance, in China (Guizhou Province), corn that was dried over burning briquettes could contain very high levels due to a high fluorine content of the coals and high-fluorine clay binders. In addition, fluorine can be absorbed into food (e.g. potatoes) stored under these conditions. The problem is not inconsiderable – around 10 million people have been estimated to suffer from dental and skeletal fluorosis. • Thallium: this mineral is usually present in low amounts in soil, although higher levels are associated with mining, smelting works, industrial sites, agriculture and urbanisation. Toxic symptoms include depression, insomnia and various nervous disorders. For instance, in 1979 an outbreak of poisoning occurred in Germany which was attributed to crops grown near a cement works at Lengerich. Domestic animals in the area also had high levels in their liver and kidneys. 27 Excessive amounts of fluoride can result in incidents of acute poisoning. This is usually characterised by gastrointestinal upset, which can progress to electrolyte imbalances and neurological and cardiovascular problems. It is of interest that in 2009 the American Association of Poison Control Centers reported 24,547 exposures involving toothpaste with fluoride. Of these, 378 cases were treated in emergency departments. Exposure involving vitamin complexes containing fluoride were reported by 1,456 individuals, with 107 cases treated in the emergency department (Bronstein 2010).

Unanticipated exposure problems can occur in clay-handling professions due to repeated contact with toxic components, notably crystalline silica. Long-term exposure during mining and processing operations, through the inhalation of mineral dust, can result in chronic pulmonary disorders such as pneumoconiosis – commonly known as ‘grinder’s disease’, which is characterised by fibrotic changes in the lungs. Coalworker’s lung is a form of pneumoconiosis, as is kaolinosis due to inhalation of kaolin particles – asbestosis and silicosis (potter’s rot) are due to asbestos and silica exposure, respectively. Talcosis is associated with chronic talc inhalation, and over-use of talc can even be responsible for severe respiratory distress in infants (Lopez-Galindo 2007). The following caution with regard to talc appeared 1949: ‘The use of Talcum powder about open wounds, even for dusting surgeons’ gloves, should be avoided. The particles act as foreign bodies, producing tubercles and fibrosis; in the peritoneum they cause adhesions’ (Sollman 1949). There have been concerns expressed with regard to the use of talc on the perineal area in women and a potential carcinogenic effect

Minerals and Lung Disease

Hans Presser, representing the trade of pottery, 1605. From the records of the Nürnberger Zwölfbrüderstiftung, Stadtbibliothek Nürnberg.

(Left) Blue asbestos (crocidolite) from the Wittenoom Mine, Western Australia, which was closed in 1966. (Right) Asbestos (tremolite) silky fibres on muscovite (mica), on display at the Natural History Museum, London. The term ‘asbestos’ refers to six different silicate minerals composed of long thin fibrous crystals that once had diverse commercial applications, mainly in the building trade. Longterm exposure has been linked to the development of a rare form of lung cancer (mesothelioma). The use of asbestos in most parts of the world is now banned. (Image on left courtesy John Hayman; image on right courtesy Aram Dulyan)


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on the ovaries. Carcinogenicity appears to be linked to the proportion of long fibres found in the samples. Asbestos exposure has also resulted in deposition of asbestos fibres in ovarian tissue (Langseth 2008; Lopez-Galindo 2007).

Soil Science: A New Look at Urban Earth

While there is increasing concern about the use of chemicals in the home, few of us would truly realise the extent of the problem in our own backyards. Soil acts as a filter for water everywhere on the planet. There is no escaping it. Therefore, what we put into the soil can stay there, quite often having a cumulative effect. In some urban areas pollutants such as leaded petrol and paint continue to contaminate the environment. They are not easily eliminated, with soils becoming a toxic reservoir of our past mistakes. This not only refers to lead, but also to cadmium, copper, aluminium, arsenic and zinc – as well as agricultural chemicals (particularly pesticides) and other contaminants such as dioxin (Abrahams 2002).

The Health Effects of Pollution. (Courtesy Mikael Häggström, Wikimedia Commons, Public Domain)

It is these types of problems that have lifted the subject of soil remediation from obscurity and propelled it to the forefront of environmental science. It is a massive topic, the value of which cannot be underestimated. Indeed, less evident soil contaminants have the potential for profound health consequences. For instance prions, such as those responsible for the neurodegenerative disease spongiform encephalopathy (Creutzfeldt-Jakob disease; CJD), can be adsorbed

A diversity of chemicals has been commonly found on farm sites and in the kitchen cupboard – often put away with little regard for their toxic potential. In the past innumerable poisonous chemicals were easily accessible, and incidents of poisoning were not uncommon. Early twentieth century examples, displayed at Herberton Historical Village, Queensland. (Image courtesy Tony Young)

Toxic dieldrin granules being poured on a fire-ant hill. From the 1950s to the 1980s aldrin and dieldrin were widely used as crop pesticides, particularly on corn and cotton in the United States. Due to concerns about damage to the environment and human health, the EPA banned these chemicals in 1987. Similar organochlorine pesticides have subsequently also been banned. However, their replacements are synthetic alternatives – about which little is known with regard to their environmental effects. Pollution of surface and groundwater supplies continues to be a major avenue of pesticide and herbicide exposure. (Image courtesy BF Bjourson, CDC)

by clay minerals and remain infectious. Preliminary studies have shown that prion contamination of municipal wastewater treatment systems can result in their accumulation in sludge solids, as they can survive the treatment process. This also has implications for agricultural land with regard to the burial of infected animals and the need to minimise contamination of the surrounding soil (Bisi-Johnson 2010; Jacobson 2009; Hinckley 2008; Johnson 2006). While most of us are aware of the existence of antibiotic-resistant forms of bacteria and their

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problematic effect on the treatment of numerous conditions, few of us would truly appreciate the ubiquitous nature of the problem. Concerns have been expressed that animal feeds routinely supplemented with antibiotics may alter soil chemistry. A study of farm waste lagoons and nearby groundwater reservoirs has shown that bacteria in the soil and groundwater can carry tetracycline-resistant genes that are almost identical to the bacteria found in an animal’s gut. This level of transference has serious implications for the spread of antibiotic resistance in environmental systems (Bisi-Johnson 2010; Chee-Sanford 2001). French studies of wastewater use on agricultural land have shown that antibiotics (quinolones, sulfamethoxazole) can ‘represent a durable contamination of soils, and risks for groundwater contamination, depending on the physicochemical characteristics both of the organic molecules and of soil constituent’ (Tamtam 2011).

due to the fact that the excretion of coliform bacteria by sheep is five times that of a human. After substantial rainy periods, beaches and riverine situations can experience high levels of bacterial contamination that may require site closures (Abrahams 2002). Undoubtedly this has a significant effect on fish stocks and marine habitats. Contamination of marine waters can result from other sources – and have equally dramatic repercussions. Off the coast of California around 10 per cent of Sea Otter deaths are blamed on Toxoplasma infections. These are thought to be the result of cat faeces being washed into the ocean (University of California News Wire, 2002).

Problems with Poo

Merino sheep. (Courtesy Kimberly Beatty)

Antibiotic-resistant bacteria can reach the environment in diverse ways. Fruit and vegetable crops carry the risk of antibiotic contamination with the potential to transmit bacterial resistance genes. Animal manure is another avenue of exposure (Ruimy 2010; Chee-Sanford 2009; Hoese 2009; Baquero 2008; Dolliver 2008). Faecal contamination of agricultural land can be a significant problem in areas of intensive farming. For instance, the droppings produced by the sheep population of Wales (11 million) are equivalent to that of a human population of around 55 million without sewerage. This is

Sea Otter wrapping itself in kelp, Morro Rock, California. The use of certain types of clay have been investigated for the control of harmful algal blooms (Beaulieu 2005) – perhaps a selective form of activity could be extended to other forms of marine contamination to help mitigate the tragic environmental consequences for wildlife. (Image courtesy Michael L Baird, flickr.bairdphotos.com)

A Purification Effect

Clays (zeolite minerals, bentonite and hydrotalcite clays) are excellent water-purification agents. They are utilised for removing nitrogen, phosphate and diverse other contaminants from water supplies (including purification of arsenic-containing drinking water), filtering urban wastewater, animal effluents and aquatic water systems (e.g. fish tanks, water tanks), and for the prevention of algal blooms (Gilliman 2010).


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A

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These highly magnified SEM (scanning electron micrograph) images of untreated water samples show a variety of foreign components surrounded by blue biofilm: A, amoebae and bacteria; B, a large diatom and bacteria (red); C, urn-shaped object – ‘an exquisitely-formed unidentified round vesicleshaped microorganism, which may have been algal, or diatomic. Shaped like an ancient Grecian urn, the almost perfectly rounded smooth, flawless surface was made even more beautiful given its delicate structure’; D and E bacteria (red), algae (green) and a golden object described as ‘a strangely-beautiful microorganism displaying an outer surface studded with numerous projections, making it appear like a microscopic sea urchin’. (Images courtesy Janice Haney Carr, CDC)

Clay has significant environmental detoxification properties, notably for pollution control and mopup operations concerning oil spills, biodegradable pesticides and sorption of radionuclides (BisiJohnson 2010). Several forms of zeolite have acquired a useful reputation for the purification of hazardous materials, which has extended their potential uses as bioremediation agents. The structure of these minerals is integral to their capabilities. Clay mineral crystals contain channels with large cage-like openings that readily allow cation exchange, taking up or ‘trapping’ heavy metals and the like (Limpitlaw 2010). There are numerous other environmentally friendly applications for various forms of clay. Clays have been used as mineral-enriched fertilising agents, for the treatment of feedlot wastes to promote drying and granulation, as a mineral resource for the reclamation of degraded soils, supplements in farmed animal feeds, deodorants/absorbents for cat litter or damp/mould-drying products – as well as providing zeoponic substrates for greenhouses and space missions (Gilliman 2010; Ivkovic 2004).

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Hydrotalcite (magnesium–aluminium layered double hydroxide) with serpentine. Hydrotalcite provides an example of a specific product with diverse industrial uses: a fire-retardant in building materials, anti-yellowing agent for PVC, a catalyst for molecular conversions – with high purification products suitable for medicinal use as antacids or for the controlled-release phosphate drug formulations. The chloride form of hydrotalcite is suitable for phosphorus and arsenic removal from water supplies (Gilliman 2010). (Image courtesy Rob Lavinsky, irocks.com)

The discovery of the excellent binding properties of clay with some toxic herbicides has extended its therapeutic potential as a poison antidote. A high adsorption affinity for chemicals such as Paraquat has been demonstrated for various forms of clay (e.g. fuller’s earth, bentonite) and activated charcoal. Indeed, the World Health Organization recommends fuller’s earth as an adsorbent remedy on exposure to agents such as mustard gas. Israeli troops have utilised it following exposure to chemical warfare agents (Limpitlaw 2010; Tsai & Lai 2006; Idid & Lee 1996; Okonek 1982). The toxic effects of Paraquat are well known. It has even been utilised as a suicide agent by the poor, particularly in Asia, a purpose for which it is highly effective – and unpleasant. Death usually

In contrast to palygorskite, Epsom salts (magnesium sulphate, MgSO4) or epsomite, which is readily water soluble, is a highly effective purgative. In emergency situations, Epsom salts has been clinically utilised for the treatment of poisoning by organophosphorus herbicides – with excellent results (Pajoumand 2004). In addition, magnesium sulphate has significant antispasmodic properties and is also used for treating cardiac arrhythmia and asthma. (Image on left courtesy Chemicalinterest, Wikimedia Commons, Public Domain; image on right courtesy Yates, Australia)

results from serious irreparable lung fibrosis, multiple organ failure and cardiovascular collapse (Wong 2006). Importantly, zeolites can extract cesium and strontium from nuclear waste, and have therefore been utilised remedially for nuclear accident sites. Indeed, clinoptilolite was used for site clean-up operations after the Chernobyl accident in 1986. Interestingly, supplementation of animal feed with 10 per cent powdered clinoptilolite in Bulgaria reduced the radionuclides in milk, showing a 30 per cent reduction in contamination. The mineral was even added to chocolates and biscuits to ameliorate the side-effects of radiation exposure in children (Limpitlaw 2010). Zeolite was also dumped into the sea after the Japanese radiation leak at Fukushima Daini (Fukushima II) in March 2011.

Radiocontamination Issues

Palygorskite (pictured) is a form of fuller’s earth that has a detoxicant effect due to its adsorbent properties. (Courtesy www.mineraly.sk CC-by-SA 3.0 Unported, via Wikimedia Commons)

Radioactive iodine (radioiodine: iodine-131) is a radioisotope of iodine – a highly problematic by-product of the nuclear industry, exposure to which involves a particular risk for developing thyroid cancer. Iodine-131 was the toxin of greatest concern during open-air atomic bomb


contamination of the food chain. In addition, there are significant concerns with regard to radioactive materials in food supplies – which have been detected in a range of produce (including spinach, tea leaves, milk, fish and beef ) up to 200 miles (320 kilometres) from the nuclear plant. Inside the 12-mile evacuation zone all farming has been abandoned (Tabuchi 2011; Reuters 2011).

Stream running through serpentine rock. Some minerals have insulation qualities that suit them for use in nuclear installations. Serpentine has been used as a dry filler for the steel jackets inside some nuclear reactors. It has also been used for radiation shielding and as an aggregate in the concrete used in nuclear reactors. (Image courtesy Alex Zorach, Wikimedia Commons, CC-by-SA 3.0 Unported)

testing in the 1950s, and after the Chernobyl disaster in 1986. It also formed a large part of the contamination hazard in the first weeks after the Japanese nuclear crisis of March 2011. The problems associated with the environmental consequences of radionuclide exposure following a nuclear accident can be illustrated by Chernobyl. Fallout reached as far as the United Kingdom, with radiocesium contamination of plants eventually being transferred through the food chain to grouse, sheep and honey. This resulted in long-term hazards – and bans continue to remain on some foodstuffs, including produce from sheep grazed on affected lands. The quarantine period has lasted over 100 times longer than originally estimated. Indeed, in some areas of the former Soviet Union, the consumption of wild foods (fruit, berries, fish) will remain under restrictions until at least 2050 (Abrahams 2002). Similar reservations have been expressed after the Japanese radiation leak in 2011. The level of radiocontamination of seawater along the coastline has been of particular concern – a factor that will increase as rain washes fallout from the atmosphere into the ocean. This has widespread potential for substantially greater

Mary Kathleen uranium mine, Queensland, abandoned open pit. (Courtesy Martin Griessman)

Uranium ore. (Courtesy US Geological Society)

Ranger uranium mine, Kakadu. Radiation contamination of the environment is an ongoing concern at some sites in Australia. There have been more than 150 leaks, spills and licence breaches at the Ranger uranium mine since it opened in 1981. A report in the Age by Lindsay Murdoch, entitled ‘Polluted water leaking into Kakadu from uranium mine’ (13 March 2009), noted that the Ranger mine was leaking 100,000 litres of contaminated water into the ground beneath the Kakadu National Park every day. (Image courtesy Dustin M Ramsey, Wikimedia Commons)

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a;

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Different grades of zeolite produced by Zeolite Australia, Werris Creek, NSW. Zeolite is a type of hydrous aluminium silicate, some forms of which produce extremely beautiful crystals that can be found in all types of rock. There are around 600 different types (the largest group of silicates) – and another 40 have been synthetically produced.

Zeolites have a broad spectrum of medicinal use, particularly in applications that require specific adsorption and ion-exchange properties (Ivkovic 2004). • Antibacterial: zeolites have bactericidal and fungicidal properties useful for treating urinary tract infection and preventing dental plaque formation. • Wound healing: powdered zeolite can promote healing of wounds and surgical incisions. In Cuba, clinoptilolite has been widely used for treating topical wounds in horses and livestock. • Antidiabetic: clinoptilolite has shown experimental activity against the side-effects of diabetes, notably polyneuropathy. In animal studies, silica has also shown diabetic-preventive activity. • Antioxidant: clinically, clinoptilolite has potent antioxidant properties with potential for use in chronic disease conditions such as diabetes, as well as cancer. • Detoxicant: a urease–zeolite preparation has been

used to remove urea from blood in patients with uraemia. Zeolites can be used as a filter medium for exchanging ammonia during haemodialysis and haemoperfusion procedures. • Antidiarrhoeal and antacid formulations can incorporate zeolite: a sodium carbonate– clinoptilolite formulation was shown to be a safe, effective antacid in patients with ulcers. • Osteoporosis: a synthetic zeolite has shown potential for improving bone cell (osteoblast) formation and activation, suggesting its use for osteoporosis. • Immune function: zeolite formulations have shown an immune-supportive role with suggestions of potential use in immunosuppressed individuals. Silica, silicates and aluminosilicates also have immunomodulatory properties that may be similarly beneficial. • Medical imaging procedures: gadolinium zeolite has been a useful contrast medium for MRI scans of the gastrointestinal tract.


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The environmental cost of mining clay. The use of clay for building works can be associated with unexpected environmental concerns, as this scene of deforestation in Rio de Janeiro, Brazil (2009), demonstrates. They clay is being used in construction projects in Barra da Tijuca. (Image courtesy Alex Rio Brazil, Wikimedia Commons, Public Domain)

Into the Unknown: Microbes for the Future

Gold on calcite from Bronzewing Mine, Western Australia. (Courtesy Rob Lavinski irocks.com)

Gold was discovered at Kalgoorlie in 1893, and has been mined there ever since. This is the ‘Super Pit’ at Kalgoorlie, Australia’s largest open-cut gold mine. (Courtesy Brian Voon Yee Yap CC-by-SA 3.0)

In the late 1990s the Australian CSIRO and BacTech Pty Ltd (a Western Australian mining biotechnology firm) discovered some rare cyanobacteria with detoxification properties that could thrive in salty, toxic environments. This was an important discovery because cyanide, which is used during gold extraction, produces toxic by-products, among them thiocyanate. These unusual microbes were found to have the ability to purify cyanide-contaminated wastewater, resulting in a remarkable 15-fold

reduction in toxicity. Further investigation revealed other microbes, hitherto unknown, that could also break down thiocyanate. Studies of the use of bacteria from the genera Thiobacillus and Halomonas, which were isolated from the Youanmi mine in Western Australia, determined that phosphate was the only additional nutrient required for thiocyanate degradation. The bacteria degraded the toxin to form ammonium, sulphate and carbon dioxide. The potential use of microbes as a waste decontaminant to clean up numerous mining operations and provide clean recycled water has significant environmental implications (Stott 1999; CSIRO 1998). These discoveries led to the development of a range of other useful strategies for mining enterprises. Interestingly, gold deposits found in a number of sites in Australia, Venezuela, Alaska and South Africa have been attributed to bacteria and cyanobacteria. Few

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of us would appreciate that gold can be accumulated by microbes (e.g. Bacillus subtilis, Escherichia coli IAM1264, Pseudomonas maltophilia IAM 1554). Indeed, the cyanobacteria Plectonema boryanum UTEX 485 can recover gold from industrial waste solutions such as gold mining waste and gold electroplating effluents (Lengke 2006). In most mining operations, cyanide-contaminated tailings are stored in open-air dams where the cyanide undergoes slow natural degradation. This process results in the formation of stable cyanide compounds, particularly under alkaline conditions. Cyanide complexes that are formed due to the reaction of cyanide with sulphur often yield thiocyanate, although other metal cyanide complexes can result from copper, iron, zinc or nickel. These are stable and able to resist natural degradation, leading to high cyanide concentrations in ‘tailings dams’. Wildlife casualties occur when birds and animals drink the contaminated water. Dam leakages have been linked to environmental disasters – usually involving polluted river systems that compromise local water supplies and kill riverine animals (Brinne 2000).

Mine tailings pollute the Rio Tinto (Red River) in southwestern Spain. The Rio Tinto is very acidic, with a very high dissolved iron content. The microbes that survive in such an environment are unique – with more than 1300 different organisms having been collected, including bacteria, yeasts, fungi and algae. The unknown world in which these micro-organisms exist may well reflect a Marsstyle environment of interest to scientists surveying the Red Planet (NASA Press Release, 8 April 2003). (Image courtesy Carol Stoker NASA, Ames Research Center)

 If there is a lesson to be learned from the sum of the rather unlikely investigations involved in humanity’s use of bizarre remedies, it would be the appreciation of the value of all aspects of our planet. The world’s floral, faunal, insectivorous and microbial diversity cannot be underestimated. Nature’s beneficial products have originated from some highly unusual, unexpected and, at times, somewhat questionable sources. In an environment where disruption is now commonplace there can be unforeseeable long-term consequences associated with a loss of biodiversity. Even minor changes affecting soil microorganisms could easily influence the diversity needed to produce new antibiotics. It may come as a surprise to learn that soil is reported to be the most biodiverse environment on Earth – with vast potential for the discovery of new microbes, many of which have medicinal potential. This only serves to highlight the fact that environmental mismanagement can have unknown long-term repercussions – with detrimental consequences that few of us can truly appreciate. There have been a number of major projects examining Australia’s biodiversity in the search for new compounds, most of which have been undertaken in collaboration with the CSIRO. This has not only involved an evaluation of plant chemistry (phytochemistry) – all manner of fauna and insects, as well as microorganisms and marine chemistry, have been examined. In particular, bacteria continue to be a rich resource for new technology, as the discovery of cyanide-binding and gold-digging microbes from Western Australian mines illustrates. Recent research has even suggested sampling termite and ant mounds for gold dust – the insects excrete heavy metals accumulated during their foraging. Such deposits at the nest site act as a perfect indicator for hidden soil components. There are also numerous plant and microbial genera that have made unique adaptations to deal with the arid inland conditions of the continent. Some are toxic, others have insecticidal, antibacterial and anticancer potential. Their story is one that has only just begun and the chemical analysis is bound to bring many new surprises.

Chapter 6

A DESIRE FOR DIRT? Ancient Art in an Ancient Landscape

Manlike petroglyph (rock engraving) around 25 cm long, from Mutawintji National Park, near Broken Hill (880 kilometres west of Sydney), New South Wales. Petroglyphs are exceptionally durable images that were incised or carved into the rock. (Image courtesy Peter Woodard).

Baiame’s Cave near Milbrodale, south of Singleton, NSW. Centred on the rear wall is another depiction of Baiame, who came down from the sky to the land to create the rivers, mountains, caves and forests. (Image courtesy Tammin Wright, Wikimedia Commons, CC-by-SA 3.0)

Petroglyph (1.7 m long) in Ku-ring-gai Chase National Park, Sydney, incised into Hawkesbury sandstone. This possibly depicts Baiame, a powerful magical Creator God or Sky Father for Aboriginal people. Notable features of the image are the swollen knee and the lack of a neck. (Image courtesy Peter Woodard)

Over the millennia humanity has found clay and ochre to be among the most versatile and useful products on the planet. The many ancient decorative and artistic uses of these substances provide tantalising glimpses of forgotten cultures and traditions lost in time – often reflecting a metaphysical dimension. The issues of spiritual and mental health were extremely important to many healing systems. This aspect of life was frequently addressed in simple household or tribal customs – and were an integral part of the great medical traditions of China and India. In many ways, the artistic and decorative uses of clay and ochre reflected such traditions. Its deployment as a body paint for celebrations, initiation ceremonies, healing, mourning or fighting parties was a very public demonstration of emotion and custom. The subject takes on a fascinating turn when examining the medicinal use of clay, which ranges from bandages 245

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to antidiarrhoeal remedies. Even the equally intriguing practice of eating clay (geophagy) was recorded in the ancient literature.

Lake within Clearwell Caves, Forest of Dean, Gloucestershire, England. The bright red colour of the roof is due to iron ochre pigment, which has been mined from these caves for at least 7,000 years (since the Middle Stone Age). Yellow, orange, red, brown and purple ochres continue to be hand-extracted from the site. During the Roman occupation it was employed as an iron ore mine. (Image courtesy Andy Dingley, Wikimedia Commons)

Ceiling of ‘The Keeping Place’ art gallery and studio, home of the Tiwi art cooperative Ngaruwanajirri, at Wurrumiyanga on Bathurst Island in the Tiwi Group, off the coastline of the Northern Territory. The Tiwi people are famous for their carvings and artworks. (Image courtesy Satrina Brandt)

Ornamentation and Display

Aboriginal dancers at Augustus Downs Station, Queensland, June 1946. From the photograph albums of Alfred Amos, valet to the Duke of Gloucester, Governor-General of Australia, 1945–1960. (nla.pic-vn4660686-s387-v)

Carved poles from the Tiwi Islands. (Courtesy Tourism NT, www.travelnt.com)

Tribal markings. Illustration for the legend ‘Gheerlahngahwombawomba, the bird that hangs to the bibbil trees’, from a collection of original drawings by Nora Heysen to illustrate Woggheeguy: Australian Aboriginal legends, collected and written by K Langloh Parker, 1930. (nla.pican23217904-v)

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The famous archeological site, Lake Mungo, is the ovalshaped brown area in the centre of this aerial image, bordered on the right by the lighter colour of the sand dunes known as the Walls of China. The lake site once held water, but for around the last 16,000 years it has been dry, forming part of the desert landscape. (Image courtesy NASA, World Wind)

The Australian Aborigines’ use of clay for decorative purposes was observed from the early days of contact. Joseph Banks commented: Besides these extraordinary bones [through the nose] they had necklaces made of shells neatly enough cut and strung together, bracelets also if one may call by that name 4 or 5 ring[s] of small cord wore round the upper part of the arm, also a belt of string tied round the waist about as thick as worsted yarn, which last was frequently made of either human hair or that of the Beast calld by them Kangooroo. Besides these they paint themselves with the colours of red and white: the red they commonly lay on in broad patches on their shoulders or breasts; the white in stripes some of which were narrow and confined to small parts of their body, others were broad and carried with some degree of taste across their bodies, round their legs and arms &c, they also lay it on in circles round their eyes and in patches in different parts of their faces. The red they usd seemd to be red ochre but what the white was we could not find out; it was heavy and close graind almost as white lead and had a saponaceous feel, possibly it might be a kind of Steatites (i.e. it was Kaolin or pipeclay). We lamented not being able to procure a bit to examine (quoted in Beaglehole 1963).

The use of ochre as a body paint is very ancient. Its deployment for ceremonial body markings is important in many cultures, including Australian Aboriginal traditions – as was its use for decorating sacred boards, and executing cave and bark paintings. Indeed, ochre has been found at archaeological sites

The use of ochre, particularly red ochre, has permeated Aboriginal society since antiquity. Its use on ancient artefacts, rock art and for body decoration traditions is evidence of this – yet its social value would be most clearly demonstrated by its use in funeral rites. The earliest, and most spectacular, evidence of its use comes from the Lake Mungo site in western New South Wales. The unearthing of Mungo Man, who died around 40,000 years ago, revealed that he had been coated with red ochre when he was buried. He, and Mungo Lady (whose body was cremated before burial), are the oldest known Aboriginal burials in Australia (Mayell 2003; Peterson & Lampert 1985). (Image courtesy James Maurice Bowler, CC-by-SA 3.0 Unported)

in Australia dated around 55,000 years ago. The yellow and white clays (the latter being ‘pipeclay’) were considered more suitable for painting and body decoration – while red has been more highly prized as a medicament in the Northern Territory. White clay was equally well regarded as a remedy in other parts of the country. White clay, which is often readily available along riverine sites, is a type of kaolin (hydrated aluminium silicate) (see Table 5.1, Chapter 5) – with analysis showing a high aluminium and silicon content (92.6%).

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Mimi spirits in the Angangbang gallery, under Nourlangie Rock, Kakadu National Park. This Aboriginal painting depicts extraordinarily thin fairy-like spirits that reside in rock crevices, where they cannot be dislodged by the wind. These were the spirits that taught the Aboriginal tribes of Arnhem Land to hunt, to prepare kangaroo meat, and the use of fire. The most ancient signs of the Aboriginal occupation of Australia have been found at a couple of sites in the Northern Territory, which are estimated to be 50,000–60,000 years old. (Image courtesy Dustin M Ramsay, Wikimedia Commons)

Ancient Traditions: Ochre and Art

Kaolin-type clays have been utilised for ornamentation in many countries. One example is the unique clay masks fashioned by the Asaro mudmen of Papua New Guinea (Kabiufa, Eastern Highlands). Kaolin clays are normally whitish in colour, although the purity can differ according to its mineral composition and the type of processing it has undergone. Heat treatments (usually baking) have a significant influence on clay colour and chemistry – for example, khaki, whitish and greyish clays become calcined, which makes for a richer and brighter hue. Yellowish clays tend to turn brick red due to the iron oxide in goethite, which changes to haematite (Ekosse 2010). (Image courtesy Jialiang Gao)

Aboriginal art has an ancient spiritual dimension, utilising colours that provide an enduring link with the land around them. The paintings at many rock sites have been replenished over time, the artisans carrying on traditions that are lost in time. It is this spiritual dimension that has deep cultural and healing overtones. Yet their preservation has not been an easy task. A report by John Clarke in 1976 provides a great deal of information with regard to the manner in which the Wandjina paintings of the Kimberley of Western Australia were executed: ‘The pigment [huntite: magnesium calcium carbonate] was probably chosen by the Aboriginal artists because of its intense white colour, high opacity, and fine particle size. Problems with its durability were of little importance … The paintings were to be visually spectacular and were not required to last long (probably no more than the lifetime of an individual) as they were very often over-painted

A DESIRE FOR DIRT?

Tombs, Aboriginal rock art site, Mount Moffatt, Queensland, photographed by Frank Hurley 1949. (nla.pic-an23148484-v)

Aboriginal cave painting, photographed by Gordon Donkin, Kimberley Expedition 1950. (nla.pic-vn3821617-v)

or touched up. The Aboriginal explanation is that the paintings are the work of a “spirit being” who returns from time to time to repaint or repair paintings.’ Unfortunately, even at this time these paintings were ‘deteriorating at an alarming rate. The old men, restricted to missions or Aboriginal communities, are unable to visit their art sites to repaint or restore the paintings. Even if they could, their traditions have changed, their art is now influenced by European values, the song and ceremonies which were part of the art have been largely forgotten.’ Enormous problems have been associated with the preservation of these artworks. This usually involves chemical discrepancies at the rock site – as well as the quality of the paint utilised: ‘The problems of conservation lie with the pigment and its method of application. The paintings are generally on the walls and roofs of shelters … which are very stable, strong rocks, virtually at equilibrium with the present climate.

Aboriginal rock art in the Wandjina style, Kimberley region, Western Australia. The Wandjina were cloud and rain spirits of the Dreamtime. They were depicted in black, red and yellow on a white background. These very powerful spirits punished those breaking the law with floods, lightning and cyclones (Flood 1997). (Image courtesy Claire Taylor, flickr)

The huntite is alkaline (pH 9.75) whereas the rock is slightly acid (abrasion pH 6.45) which causes chemical instability at the interface, an ultimate flaking of the paint layer.’ Ochre was equally problematic. It was prepared as a thick water-based suspension which had, in some places, been applied in many layers over the centuries. However, the particles within did not bond tightly together: ‘when water is applied to the surface it is readily absorbed into the surface layers by a system of capillaries, entrapped air is then expelled with enough violence to disrupt the paint layer. In the field this means that paintings exposed to water are quickly destroyed’. Hence, run-off water or rain blown into rock shelters quickly resulted in erosion of the images. Changes in humidity could also cause flaking due to repeated alteration in moisture levels within multi-layered paintings: ‘The aboriginal tradition of over-painting previously painted or even dirty surfaces causes further problems by creating a build up of alternating layers of white and coloured pigments … [where] failure due to flaking usually occurs at an internal paint junction due to incompatibility of the pigments and differential expansion with moisture changes’. However, simple single-layer red (hematite) paintings can remain in good condition even though they may be older and, at times, in more exposed positions.

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Aboriginal hand art on cave wall, Carnarvon Range, Queensland, photographed by Frank Hurley sometime between 1910 and 1962. (nla.pic-

Ubirr art site, Kakadu National Park, Australia. Red ochre, which is considered to be the blood of ancestral beings, has great significance to desert cultures. It is endowed with special curative, protective and strengthening properties. (Images courtesy Thomas Schoch, CC-by-SA 3.0)

Tom Petrie (1904) observed many ceremonies where Aboriginal people anointed their bodies with animal fat and charcoal, which imparted an extremely glossy shine to their appearance. Their bodies were adorned with red, yellow and white designs: In contrast to white people, the aborigines wore red when mourning for the dead … red was put all over the body, even the face, and then for deep mourning (for instance, if the deceased were a brother or sister) splashes of white clay relieved the monotony here and there. It was only the old people who troubled to mourn thus, however; and the old gins in addition wore feathers coloured red, stuck in little bunches here and there in the hair with bees’ wax … The red colouring used for mourning was not the same as that used for reddening noses.1 They

Barramundi: rock art utilising red ochre. (Courtesy Frank Busch, Wikipedia Commons Project, CC-bySA 3.0 Unported).

were both got from stones, but the latter was more uncommon, and the Turrbal tribe could only obtain it by barter with inland blacks. In both instances, two stones were rubbed together, and the powder coming from them just rubbed into the skin, but the mourning colour was a dull red, while the other was beautifully bright and glossy … When putting on white clay (‘banda’) the natives wet a piece well with their tongue, and so plaster it on. The yellow colouring … used at other times (never for mourning) was obtained from a toadstool (Polysaccum olivaceum) which grew, strange to say, always beside a big ants’ nest … They were big and round, these toadstools, and were full of a yellow powder which the blacks rubbed 1 ‘On any important occasion the black men always had their noses red; bodies were painted in different styles, but noses were all the same. So it was with the boys’ (Petrie 1904).

A DESIRE FOR DIRT? dry into their skins. White toadstools of the same shape are common enough.

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Mines from Prehistory

Petrie also provides an interesting description of the wonderful ‘fireworks’ of a corroboree gathering: ‘Kundri’ men would come running down the roadway to the big ring, with small firesticks in either hand, and these they would shake and brandish in front of the boys as they ran round the ring, making a great noise all the time. The men and women on the outside added to the row by singing and dancing, and they also carried firesticks, twisting them into all shapes and forms with their movements. It was a sight worth seeing. Let us in fancy look at it in the solitude of the bush. The dark forms ever on the move, the firesticks twisted into fantastic shapes and hoops of fire, lighting up the little sober faces of the boys as they sat round the ring watching the performance.

Ancient mine sites in Australia were primarily utilised

Visually, minerals provide a wonderful array of colours, shapes and sizes that are often transformed into objects of desire by the clever jeweller. However, less appreciated is the extraordinary array of uses they have had since antiquity – applications that have endured to this very day. Australian Aborigines mined diverse types of rock: amphibolite, andesite, basalt, blue metal, chalcedony, chert, diabase, granite, greenstone, greywacke, ironstone, limestone, mudstone, obsidian, porphyry, quartz, quartzite, sandstone, silcrete, silicified stone, siltstone and trachyte. In New South Wales silcrete extraction, with chert, quartz and quartzite, was relatively common (NSW DPI 2007). (Image courtesy Mila Zinkova)

‘Round the ring they jumped as Borah had done, their long tails waggling behind them.’ Illustration for the legend of Borah the kangaroo, from a collection of original drawings by Nora Heysen to illustrate Woggheeguy: Australian Aboriginal legends, collected and written by K Langloh Parker, 1930. (nla.pic-an23217591-v)

Drawing by Tommy McCrae, a member of the Wahgunyah tribe on the River Murray, 1880. (nla.pic-an6431252-9-v)

The Koonalda Cave in South Australia is the site of a rather extraordinary ancient Aboriginal flint mining operation that extended around 75 metres below ground – and up to 300 metres from the entrance of the cave. (Image courtesy Kevin Moore, flickr)

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by Aboriginal people as sources of ochre, and as rock quarries for weapons and implements. While ochre was often simply dug out of the ground or around river beds, some sites were especially prized. There are over 400 mine/quarry sites in eastern Australia – and even more have been found in the western part of the continent. The largest is Wilgie Mia in Western Australia, although other sites of importance include Bookartoo (Parachilna) in South Australia, and the Campbell Ranges of the Northern Territory. At different mines different extraction strategies were employed. At Wilgie Mia pole scaffolding and wooden platforms were used for digging the clay out of the cliffs – while at Mount Rowland, Tasmania, women used wooden chisels and stone hammers to mine the ochre, which was then stored in kangaroo-skin bags. Mining operations in a few places were quite extensive (DPI NSW 2007; Peterson & Lampert 1985). Ochre and tools were major trading products, and some groups travelled long distances to trade goods. Indeed, Queensland trading parties could trek from Cloncurry (almost 800 kilometres inland from Townsville in the north) to the Yarrakina ochre mine (Parachilna) in the Flinders Ranges, South Australia. Queensland-made shields or light spear shafts from New South Wales were bartered for the sought-after iridescent ochre of this area. This was one of the more highly prized ochre resources: ‘Usually, these highly valued ochres have a silvery sheen caused by an admixture of some other element such as free mercury (cinnabar) in the case of the Parachilna (Bookartoo) ochre deposits, or tiny fragments of mica’ (Peterson & Lampert 1985). Aborigines who travelled from Alice Springs in the Northern Territory would carry 25 kilogram blocks of the Yarrakina ochre over 1000 kilometres on their return trip. Interestingly, in more recent times, ochre from an equally large production centre at Rumbalara, 200 kilometres south of Alice Springs, was used for the manufacture of camouflage paint during World War II (DPI NSW 2007). Wilgie Mia has been a significant ochre resource for Aboriginal people for an extraordinary period of time. ‘Wilgie’ means ochre or pigment. The mine, which today exports ochre for commercial use, was added to the Australian National Heritage List in 2011. Archaeological excavations, which have recovered tools and equipment from the site, reveal that it has been in use for 27,000–40,000 years.

A range of coloured ochres deepening from gold to crimson was obtained from the ‘Ochre Pits’ in central Australia (West MacDonnell National Park, Northern Territory). The site belongs to the Western Arrernte people. (Image author Toby Hudson, Wikimedia Commons, CC-by-SA 3.0 Unported)

Lyndhurst ochre quarry, South Australia. The site was one of the great Aboriginal trade routes from the Northern Territory and Queensland to the South Australian coast. The nearby outback town of Lyndhurst, which was originally a railway siding in 1878, is at the crossroads of the Strzelecki Track and the Oodnadatta Track. (Image courtesy rogersmithpix)

This has led to suggestions that it may be considered among the world’s oldest mining operations still in use. The mine, which is around 30 metres across and reaches a depth of 20 metres, is estimated to have produced around 40,000 tonnes of ochre and rock. The ochre has been highly prized throughout Western Australia due to its lustrous sheen, glow-in-the-dark properties and non-irritant qualities (does not burn the skin) (www.environment.gov.au/heritage/places/ national/wilgie-mia). Much of the clay is iron-rich, containing good amounts of a fine-grained haematite that is responsible for the red colour (Clarke 1976).

A DESIRE FOR DIRT?

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Ancient Earth

Spongolite. Rebecca Creek, on the west coast of Tasmania, was a source of spongolite for Aboriginal people. This is a light, porous type of stone that was particularly useful for tool-making purposes, and continues to be employed by the building trade. It has a somewhat abrasive character due to the fact that it originates from fossilised sponges mixed with silica. Today spongolite is mined at Mount Barker, Western Australia. (Image courtesy Keith Colleran, Tropistone)

Aboriginal legend considers that the Wilgie Mia ochre mine in Western Australia was created in the Dreamtime when marlu, the red kangaroo from Kalbarri, was speared near the coast. He travelled east, following the hills to the Weld Range, dropping spots of blood along the way. At Little Wilgie Mia he bled considerably, creating a yellow ochre site. Where he died at Wilgie Mia his marlu yalgu (red kangaroo’s blood) formed the red ochre. His spirit resides in the hill beside the mine. Other coloured ochres represent different parts of the marlu: yellow ochre for the liver and green ochre for gall. (Images courtesy Chid Gilovitz, www. chidgilovitz.com)

Eruption of Mt St Helens, Washington State, USA, 1980. Medicinal clay originates from volcanic mud and ash deposits. Bentonite is a general term to describe the rocks that form volcanic ash beds. The layered sedimentary deposits accumulate during a volcanic eruption, when glassy particles are formed by the rapid cooling of the magma thrown into the atmosphere. Mineralogical variations result from the chemical characteristics of the volcanic glass and the local water chemistry. In acidic environments kaolinite is formed, in mildly alkaline situations (seawater) smectite results, and zeolite in highly alkaline environments (Williams & Haydel 2010). (Image courtesy CDC)

The medicinal use of various earths (soils and clays) has been known since very early times. Clay was deployed by the ancient healers of Mesopotamia (2500 BC), Egypt and Greece. The great physicians Hippocrates and Aristotle were familiar with distinct classifications for the different types of earth. Special forms of clay were named for their origins or their therapeutic reputation: Terra Samia (Samian clay), Terra Lemnia (Lemnian clay), Terra Cimolia (Cimolian clay), Terra Sonoptica, Terra Eretria and Terra Negra were but a few of them (Carretero 2002). The Strigian Earth, Terra Sigillata Strigoniensis, from Silesia (Polish border region), and the red-coloured clay from Lemnos gained particular fame. Terra Lemnia clay was mixed with goat’s blood and pressed into pellets and stampedwith a goat seal – this practice gave rise to the name Terra Sigillata (sealed earth).2 2 For centuries the original Turkish Terra Lemnia was in great demand. By the sixteenth century, a wide variety of coloured earths was available, stamped with various Turkish characters. However, not all were of equal quality and a fair number of ‘counterfeit earths’ were to be found. Paracelsus (1536) mentioned the use of Terra Sancti Pauli (a white Maltese earth), although the genuine article was often substituted with washed white clay. Terra Sigillata was plentiful around this time – although much of it was ‘taken from the next dirt heap’. A few centuries later, in the mid1700s, Strigian clay (Terra Sigillata Strigoniensis) suffered similarly from product falsification (Dannenfeldt 1984).

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In the 2nd century AD, when the Greek philosopher and physician Galen returned to Rome after a trip abroad, he had procured 20,000 of these ‘lozenges’ for use as an anti-poison and healing remedy. Doubtless a bit of canny salesmanship ensured their subsequent popularity in the marketplace (Abrahams 2005; Dannenfeldt 1984). Cimolian Earth was mentioned by Pliny the Elder in his encyclopaedic Natural History (AD 77–79). He recorded: Of cretaceous [chalky] earths there are several varieties; and among them, two kinds of Cimolian earth, employed in medicine, the one white [probably bentonite] and the other inclining to the tint of purpurissum [purple]. Both kinds, moistened with vinegar, have the effect of dispersing tumours and arresting defluxions. They are curative also of inflammatory swellings and imposthumes [abscess] of the parotid glands; and, applied topically, they are good for affections of the spleen and pustules on the body. With the addition of aphronitrum, oil of cypros, and vinegar, they reduce swellings of the feet, care being taken to apply the lotion in the sun, and at the end of six hours to wash it off with salt and water. In combination with wax and oil of cypros, Cimolian earth is good for swellings of the testes. Cretaceous earths, too, are of a cooling tendency, and, applied to the body in the form of a liniment, they act as a check upon excessive perspiration: taken with wine, in the bath, they remove pimples on the body. The most esteemed of all these earths is that of Thessaly: it is found also in the vicinity of Bubon in Lycia. Cimolian earth is used also for another purpose, that of scouring cloth. As to the kind which is brought from Sardinia, and is known as ‘sarda’, it is used for white tissues only, and is never employed for coloured cloths. Indeed, this last is held in the lowest estimation of all the Cimolian earths; whereas, that of Umbria is more highly esteemed, as also the kind generally known as ‘saxum’. It is a property of this last to increase in weight by maceration, and it is by weight that it is usually sold, Sardinian earth being sold by measure. Umbrian earth is only used for giving lustre to cloths.

A German translation of a 1583 Latin work on the subject by Berthold was made by Johann Wittich (1589) and cited in Dannenfeldt (1984). In addition to its acknowledged uses for counteracting poisons, fevers and plague, this work mentions that Terra Sigillata was a popular anti-inflammatory, antihaemorrhagic and healing agent:

Naturalis Historiae: title page of Volume I of the Natural History of Gaius Plinius Secundus (1669 edition). To staunch any haemorrhaging, beat a troche of this earth into a fine powder, mix it with human saliva or brandy, make it into a paste, and place it on the wound. Bleeding from the nose can be restrained if this earth is mixed with vinegar, eggwhite, and water of tormentil, spread on a linen cloth and the cloth laid on the temples or on the nose. Congealed blood within the body caused by any fall, blow, or other casualty, can be dissolved if the earth is taken in warm wine or by drinking a drachm of the sealed earth and a drachm of stonemarl dissolved in the whites of two eggs and warm vinegar with a scruple of saffron … For burns from fire, hot water, or molten metals, wash the skin affected with fresh spring water, in which unslaked lime has been soaked overnight, and sealed earth, or dip a black hen-feather in the solution and very tenderly anoint the burn. This earth also heals all pains, inflammations, any wounds or ulcers, especially wounds of the kidneys,

A DESIRE FOR DIRT? testicles, or inward parts when it is taken internally or applied in a plaster steeped in liquid. It has been tested and found out that this Axungia Solis (‘sun-grease’)3 will heal all itches, scabs, caries, scurviness, manges, and other filthy diseases of the skin and also make the skin smooth and white if it is dissolved in spring or plantain water and the diseased skin often stroked or washed with it and dried.

Wittich reported that this Axungia Solis, taken just as it was dug out of the goldmines and thus without preparation, cured epilepsy permanently (Dannenfelt 1984). The latter, however, appears to be a rather audacious claim. Clay bandages have long been utilised by tribal healers, and clay’s traditional use as a wound-healing agent is certainly valid. Even so, it is somewhat unexpected to find that modern medicine is using gauze-like bandages impregnated with clay nanoparticles (kaolin clay). These QuikClot Combat Gauze bandages are widely used, in situations that range from combat zones to the Coast Guard and hospital emergency departments4 (Motamedi & Sagafinia 2011; Ran 2010; Cox 2009). This appears to be a rather spectacular marrying of ancient traditional wisdom and modern technology.

These ancient traditions are reflected in a number of Aboriginal remedies. In a review of Aboriginal medicines, FS Colliver (1972) notes observations by Bolam in 1924 regarding the use of: ‘mud poultices … for drawing pus away from festers. Such poultices were made with clear earth mixed with warm water to a fairly thick consistency and the mixture was placed to a thickness of about 2” [5 cm] directly upon the open portion of the sore. This was left on for a few days, then removed, the wound cleaned with water (if available) and then anointed with goanna fat.’ This treatment continues to be in use in some places today. An article by the Warrabri Health Workers in the Northern Territory notes: ‘white ochre is smashed into a powder in a coolamon with a heavy stone, and mixed with water to make a thick cream. It is then smeared on to sores and cuts. It can also be mixed with more water and drunk’ (Warrabri nd). The known antibacterial and anti-inflammatory effects of some types of clay would certainly support these uses.

A Remedy for Wasp Stings

Medicinal Muds

Surprisingly, ancient recommendations for the use of clay have continued in practical use. Some of these were mentioned by Wittich: For any bite of a mad dog or a serpent, the sting of a scorpion, or the bite of a spider or any other poisonous animal, as well as for wounds made by poisonous weapons, one should take as much sealed earth as was necessary. Also make a paste with saliva and lay it on the wound. Or make the paste thinner and spread it on the wound. The poison will then be drawn out of the body. If the poison is already in the body, then one must drive out the poison by a sweat brought on by taking a drachm of the earth in wine or distilled water (cited in Dannenfelt 1984).

3 Axungia Solis was a term originally used by Paracelsus. Later it was applied to Terra Sigillata Strigoniensis, a brownish yellow clay sourced from the gold mines, that ‘clung to the tongue before it melted like butter’ (Dannenfeldt 1984). 4 Bandages impregnated with chitosan, a compound derived from the shells of shrimp and other crustaceans, have a similarly effective reputation (Cox 2009).

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Native wasp nest.

It is truly intriguing to find that many old therapies have survived through the ages. The antidotal use of clay was mentioned in the Queensland Agricultural Journal of 1 May 1899. A letter from Mr George Patullo ‘with regard to Wet Earth as a Bee-sting Cure’ provided the following details: The remedy has been known by me for years to be effectual, not only with regard to bee stings, but also to the sting of wasps and jumper and greenhead ants. Many years ago, whilst picknicking in a paddock, one of my boys in getting through

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary a fence disturbed a large nest of wasps, and was badly stung on the face, neck, and head. Knowing of the ‘wet-earth’ cure, I immediately daubed him with mud made with spittle, there being no water handy, and in a very short time he was free from pain. The remedy has been frequently used by myself and boys when stung by jumper and greenhead ants, resulting in almost immediate relief. I think we are too conservative with regard to simple remedies well known to ourselves, but which may not be known to others; and it would be of great benefit to the public generally were we to make known these simple remedies.

Clay (bentonite) can enter into modern remedies with similar uses, notably calamine lotion, which is used as an antipruritic to relieve itching in conditions such as sunburn, eczema, insect bites and rashes (e.g. chicken pox or allergy). It also has useful astringent and antiseptic effects that help to reduce swelling and prevent infection. This water or oilbased preparation is based on zinc oxide (5–10% solution) and iron (ferric) oxide (0.5%). The recipe in the second edition of American Pharmacy (Lyman 1948) notes the following regarding its preparation: ‘calamine [zinc carbonate] and zinc oxide are triturated into a smooth paste with glycerin and bentonite magma diluted with lime water. Then the remainder of the diluted magma is gradually added and the lotion made to volume with lime water. Care should be exercised to get a uniform paste of finely divided particles which may be readily dispersed by shaking. In the manufacture of this lotion, hydration of the zinc oxide occurs with a resulting formation of very fine particles’. (Image courtesy Probiotec Limited)

Anthony Peile (1979) likewise mentioned the use of a red ochre mixture in Western Australia for treating sores, as well as internal pain. Fat, usually from the Gould Sand Goanna (Varanus gouldii flavirufus) was first applied to the injured site or sore area to facilitate healing. Ground ochre was blended with water and cold ash added to the mixture: They rub with red ochre, they sing, they rub red ochre

on the stomach, on the navel, on the legs of a person who can’t get up, they rub on ash, they rub where the pain is inside. They tie up the head and both arms with a hair belt in order that he may get well. They sing and lay the person down. They sing and he becomes light (well). They put him in the sun, they put him in the sun in the middle of the day, sweat comes out of him. He scratches his heat, he remains quiet, they sing and then leave him to sleep. He gets up, scratches himself and feel so good. They give him water and bush tucker. He is well again.

Newborn babies were sometimes dusted with ochre and cold ash as a form of baby powder. Similar dressings have been utilised for treating burns and spear wounds: the wound was covered with warm leaves, ochre chewed and spat all over the site. Healing songs were an important part of the process. The wound was said to quickly reduce in size, form a scab cover and heal. An ochre–fat mixture was sometimes applied to a hair belt and tied on a local area (head, arms or legs) to act as a poultice. Peile commented: [these healing practices] illustrate … the Gugadja have an exact knowledge of how healing takes place with the aid of an effective medication. Spitting on wounds and sores may seem unhygienic and repugnant to us, but we must remember that the Aborigines did not have any mechanical means of spraying a medicine over the infected area of skin. They chewed medicinal leaves (such as those of Acacia ancistrocarpum, Maiden & Blakely) or ochre, with water in the mouth and in quick spurts spat the watery mixture on to and around the infected area … the reader should note the importance attached to the singing of healing songs over the patient during the application of ochre. The healing songs sung by the Aborigines over a patient help to soothe him or her and contribute to psychological well-being as soft music piped into modern hospital wards does today (Peile 1979).

The use of ochre for skin problems was also mentioned by Alistair Campbell: ‘An itchy skin condition which was known as Bubborum and caused raised dark scabs which coalesced, may have been scabies or impetigo. Aboriginals of the Yarra district, Victoria, treated this condition night and morning with red ochre mixed with a decoction of wattle bark.’ Furthermore, ‘burns were dabbed with melted fat and the parts dusted with a powder made of possum fur and wheerup (red ochre). The use of fat for burns

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was described also by Dawson. On the other hand, the aged Barak at Coranderrk, not satisfied with the treatment of a badly burnt hand, asked Miss Shaw to obtain “the blood of the tree” [kino] instead’ (Campbell 1973–74). This may have been because kino has significant antibacterial and astringent properties that would enhance the healing process. Aboriginal people, in former times, usually slept near their campfires – a situation that frequently incurred burn injuries, some of which were quite severe. Treatments included the use of crushed (chewed) glutinous orchid stem, which was applied locally – although if the burn was severe red ochre was said to have been preferred (Webb 1933). Witchetty grubs were another highly recommended burn treatment. A mashed grub paste was applied to the site which sealed it from exposure to air, thereby preventing irritation and water loss, as well as promoting a deep level of wound healing (Barr 1988). (Image courtesy binjy, flickr)

Kino encrusted around a wound in the bark of a Eucalypt tree. Kino is highly antibacterial and was once widely used by bushmen and Aboriginal people as an antiseptic healing agent for wounds (see Volume 2 for further details).

Mineral Spas Mineral-enriched ‘spa’ waters have long been considered to have special curative and tonic properties. In the Commonwealth Government Yearbook of 1913, 153 mineral springs were listed in Australia, although only two were of commercial interest as far as the provision of mineral water was concerned. The Zetz-Spa at Ballimore in New South Wales is possibly the oldest, although a settlement at Helidon Spa (established 1850) near Brisbane later became an extensive enterprise marketing the Taurina brand of mineral water. Another old spa site

Zetz-Spa advertisement in the Sydney Mail, 16 April 1898.

is at Hepburn Springs, Victoria – where the Hepburn Mineral Spring Reserve was created in 1865 to protect the site from over-zealous mining exploitation. Today it is considered to host the largest concentration of mineral springs in Australia.

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Bottled Australian spa waters display at Herberton Historic Village in north Queensland. (Courtesy Tony Young)

Brisbane premises of the Helidon Spa Water Co. pictured in The Queenslander, February 1899. The company was established in 1880 to market spring water collected from the site. (State Library of Queensland, Public Domain)

The use of medicinal clays in spa treatments, known as fangotherapy (fango is the Italian word for mud), involves the use of thermal clay baths and mud wraps etc. Pelotherapy is another term for the use of mineral clays as cataplasms or baths, usually in a heated form that promotes vasodilation and perspiration, as well as stimulating cardiac and respiratory function. Some similar therapies utilise ‘paramuds’ (a mixture of paraffin and clay minerals), very hot, applied locally. These treatments have been recommended for innumerable degenerative joint and skeletal problems – as well as skin conditions (psoriasis, acne, dermatitis) and musculoskeletal problems. In addition to pain relief in arthritis, fibromyalgia, low back pain and carpal tunnel pain, it promotes the healing of bone fractures, and has a stimulatory effect on circulatory congestion (e.g. varicose veins, cellulite) (Carretero 2002). Peat has similar cation exchange capabilities to clay and has been likewise utilised as a spa treatment (balneotherapy5) for skin disorders and painful 5 Peat mud treatments are a form of fangotherapy – a general term that covers the therapeutic use of peat, mud and clay, particularly in spas.

The Great Bath, at the Roman Baths in Bath, England. The use of thermal water and muds (including mud spas, i.e. pelotherapy) is an ancient tradition that became widespread during the Roman occupation of Europe. The thermal waters at Bath, which contain high concentrations of sodium, calcium, chloride and sulphate ions, are no longer used for bathing due to contamination concerns. Not only are the old lead pipes from the Victorian era still in use, but there is a high risk of infectious diseases due to microbial contaminants. (Image courtesy Cmyk, Wikimedia Commons, Public Domain)

Extreme habitats, such as hot springs (pictured), deep sea sediments and sea vents, and even abandoned minewaste sites, can be the home of extremely unusual microbes (extremophilic microbes or extremophiles) with remarkable environmental tolerances. These habitats have only just begun to be investigated, with these unusual microorganisms representing a huge untapped reservoir of unknown bioactive compounds (Cragg 2012). This image shows extremely clear water in a very hot thermal spring (>70° C) in Fiji, where the sediment remains undisturbed. The white blobs are gas bubbles, which can be made to rise by merely clapping the hands – while the yellow is a type of lichen. To live in an environment like this, the lichen must have some remarkable heat-tolerant properties. (Image courtesy Ian Mackay)

A DESIRE FOR DIRT?

conditions (see also ‘Shilajit: Therapeutic Humus’, page 260). In parts of Europe old peat spas from the eighteenth century are still in use. Various studies have shown that balneotherapy can be associated with increased pain relief, particularly in rheumatological conditions (Falagas 2009; Deniz 2002; Verhagen 1997, 2004). Sapropels, which are permanently inundated silted deposits from water reservoirs (bogs, riverine and marine environments), have been utilised similarly. They contain a large amount of organic matter (notably humic and fulvic acids) in a colloidal state, whereas in peat the plant matter has been humified in a marshy environment under conditions of high humidity, resulting in an increased level of solidification6 (Schepetkin 2002).

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In addition to its use as a spa additive, peat has been shown to have antioxidant, antibacterial, antiinflammatory, circulatory supportive, antiulcer and healing attributes. It has been utilised in a distilled and sterilised injectable form (the Russian product Torfot) for inflammatory mouth (stomatitis) and eye disorders (keratitis, chorioretinitis), to protect against degeneration of the retina, to heal pulmonary tuberculosis, and for diverse other chronic inflammatory disorders. Similar recommendations have been made for a Polish product (TPP: Tolpa Peat Preparation) as an immune-stimulant, antiinflammatory agent – and for a number of commercial sapropel products (Schepetkin 2002): • Peloidodistillate (Caucasian region, Russia): degenerative eye disorders, neuralgia, gynaecological inflammation. • Humisol (Tallin, Estonia): immune disorders, arthritis, respiratory tract infections. • Peloidin (Odessa, Black Sea mud): gastrointestinal ulceration, biliary tract disorders, lumbar osteochondrosis, genital inflammatory disorders. • FiBS (a specific type of sea mud): immunomodulatory and anti-allergic properties. • Eplir (oil solution prepared from lipid fraction of a specific sulphide mud): antioxidant with significant hepatoprotective properties.

Cobar Red Clay bath salts. (Courtesy Claire Maraju, Australian Native Therapies)

A peat stack in Ness on the Isle of Lewis, Outer Hebrides, Scotland. Peat is a brown-black organic sediment that forms in water-saturated sites resulting from the partial decomposition of mosses, ferns, sedges, grasses, shrubs and trees. (Image courtesy Maclomhair, Wikimedia Commons, CC-by-SA 3.0 Unported)

Mud therapy, Fijian Islands (Viti Levu). (Courtesy Ian and Sue Mackay)

6 Peat and mumie (shilajit) have been exposed to a higher oxygen influence than sapropel. This results in an intensification of oxidation processes, as well as changes in chemical and biological characteristics of the humic and fulvic acid components. Additionally, the composition of these acids in the organic–mineral matter will vary according to geographic location, and consequent vegetation differences (Schepetkin 2002).

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Shilajit: Therapeutic Humus

Shilajit (also known as mumie in some of the literature) is a humus-based brown-black resinous substance, formed over the centuries from plant remains (usually bryophytes) and mineral rocks. In general, it is estimated to be around 500–1,500 years old, although some samples from Central Asia have been dated at around 15,000 years. Shilajit is found in specific high altitude mountainous regions, notably Tibet and the Himalayas – although there are also sources in Russia, Afghanistan, China, Chile and Australia. There are three types of mumie: petroleum mumie (from transformed petroleum products deep in the mountains), plant mumie (vegetation-based mumie-asil) and mumie-kiem (from long-term humification of the guano of alpine rodents, notably the Rock Vole). Shilajit for medicinal use is the result of vegetation being compressed under rocks, undergoing significant compaction under high temperature and pressure conditions.7 The resultant organic material has a mineral component and is usually collected in the warmer summer months, when it liquefies to some extent and flows out from between the rock layers (Schepetkin 2009, 2002). Shilajit is an age-old geological material that has a rather remarkable therapeutic reputation in Indian traditions (Siddha, Ayurveda and Unani medicine) as a rejuvenative, antiageing, anti-inflammatory, immune-supportive and healing remedy. It has been utilised for the treatment of innumerable conditions that range from respiratory, urinary tract and digestive disorders, to neurological, emotional and memory problems. It has also been recommended for leprosy, anaemia, malabsorption, gout, injuries and numerous bone diseases (arthritis, osteoarthritis, osteochondrosis, fracture), diabetes, kidney and gall bladder stones, gastrointestinal dysfunction (gastritis, colitis, diarrhoea, dysentery), menstrual disorders, inflammatory skin problems (eczema), cardiovascular dysfunction (including haemorrhoids, heart disease, dropsy

and hypertension), tumorous growths, and as an antidote for snake bites and scorpion stings. Humic substances (60–80%) predominate in shilajit, with a fairly high level of fulvic acid (as well as humins and humic acid) – although diverse other components contribute to its value.8 Thus the pharmacological basis of Shilajit’s activity is likely to be due to a complex interaction of these substances, rather than a single component. Even so fulvic acid, which appears to make important contribution to its activity, has been utilised as an antiarthritic, antidiarrhoeal, antimicrobial, anti-inflammatory, cognition-protective, antioxidant and antidiabetic agent (Carrasco-Gallardo 2012; Cornejo 2011; Wilson 2011; Schepetkin 2009, 2002; Agarwal 2007). However, the fulvic acid component can vary in products from different locations: India (21.4%, Kumoan region), Nepal (15.4%), Pakistan (15.5%) and Russia (19%) (Agarwal 2007). Studies have confirmed that shilajit has a multitude of pharmacological properties. In most places (notably Russia, Nepal and India) where it is used in traditional medicine, it has been a highly regarded restorative tonic, valued by athletes, the military forces and the aged, as well as acquiring something of a reputation as a virility tonic. Recent recommendations include its use to promote healing following surgery in chronic suppurative otitis media, to stimulate bone regeneration following spinal operations and fracture treatments, and following tonsillectomy – as well as being recommended as a highly effective treatment for thermal burns and to promote recovery in pulmonary tuberculosis patients (Schepetkin 2002). 7 Indian references also mention a mineral-based shilajit classification based on copper (blue), gold (red), silver (white) and iron (brownish black). The latter, sourced from the Himalayas, is the most common and is regarded as being the most effective for medicinal use (Agarwal 2007). 8 These components include fatty acids, resins and waxy materials, latex, gums, albumins, triterpenes, sterols, aromatic carbolic acids, benzoic acid, fatty acids, hippuric acid, benzocoumarins, polysaccharides, polyphenols (e.g. ellagic acid) and phenolic lipids. The mineral components can be equally diverse, although concern has been raised regarding heavy metal contaminants such as lead, mercury or arsenic (see Carrasco-Gallardo 2012; Wilson 2011; Agarwal 2007).

A DESIRE FOR DIRT?

Research interest has focused on its antiarthritic, immunomodulatory and antioxidant activity, anxiety relief (anxiolytic, anti-stress), neuroprotective and memory enhancement activity – as well as radioprotective, vascular healing, antidiabetic, anti-ulcer, anti-allergic, anti-inflammatory, cholesterol-lowering, analgesic and antifungal properties. Shilajit also shows good potential for enhancing the activity of other drugs (synergistic effects) and can mediate the effects of altitude sickness. Recent studies have taken a particular interest in its use for memory disorders (including Alzheimer’s disease), neurological dysfunction (Parkinson’s disease, neuritis) and immune disorders such as AIDS – although clinical reports have indicated that its use is not applicable in multiple sclerosis (Carrasco-Gallardo 2012; Wilson 2011; Meena 2010; Schepetkin 2009; Agarwal 2007; Sharma 2003; Goel 1990). Investigations have established that dibenzo-ɑ-pyrones are shilajit components with powerful antioxidant, tissue-protective effects, that can penetrate the blood–brain barrier. These compounds are of interest because they can inhibit acetylcholinesterase, preventing the breakdown of the neurotransmitter acetylcholine – low levels of which are associated with poor memory and concentration problems (Schepetkin 2002).

Dirt in the Diet?

Earth can have some unusual avenues of entering into the diet. Often it appears as an incidental additive, usually from inadequate washing of vegetables – while experiments in ‘eating dirt’ appear to be a part of childhood learning experience, along with making ‘mud pies’. In many times and places in communities the world over, earth has been eaten out of hunger and desperation by the disadvantaged and famine-ravished, forced to resort to desperate dietary measures. In recent times the poor in Haiti have made ‘cakes’ of yellow dirt with butter, vegetable shortening and salt. Even rice was too expensive to be part of the staple diet (Associated Press 2008).

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Reproduced courtesy of Keep Calm-o-matic, www. keepcalm-o-matic.co.uk.

Deliberate dirt eating is called geophagy, which the medical profession has generally considered to be aberrant behaviour – an attitude, however, that does not allow for the cultural importance of ‘dirt in the diet’. Despite the perceived eccentricity of the practice, eating soil or clay has been observed in numerous cultures throughout the world, sometimes even forming a routine dietary component. Its use for deliberate geophagic purposes seems to have even formed an integral part of man’s relationship with the environment. Attesting to this is the fact that imported white clay was found next to the remains of Homo habilis at Kalambo Falls, Zambia. This suggested that the clay, which had to be imported, was a deliberate acquisition in prehistoric times (2.5 million years ago). Interestingly, the type of clay is the same that is utilised (eaten) today (Carretero 2002). Henry Burkill (1935) provided the following interesting overview: The custom of eating earth occurs in many parts of the world; those who chiefly adopt the habit, it was once said, are pregnant women, but this is now contested; the earth to which the eaters resort must not be gritty; otherwise any earth will do. But as the least gritty earths are fine clays, it is these which are used. Sometimes the earth is eaten in the condition in which it is found: sometimes

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it is partially baked; and sometimes it is thoroughly baked in the form of biscuits. There is never any reason for thinking that it serves as a nutriment, and there probably never is any useful chemical action between it and the digestive fluids; but it seems to relieve a feeling of emptiness in the stomach. The habit tends to become fixed.

Eating clay has been commonly practised by many African and Asian tribes. In some areas, the habit has even been considered to have useful poison antidote effects.

Salak, Salacca or Zalacca (Salacca zalacca) is an Indonesian palm tree, the sweet fruit of which (commonly known as Snake fruit) was mixed with clay, presumably to enhance its antidotal properties: ‘Earth is regarded as an antidote for poisons … the Semang believing it an antidote even for Antiaris: any earth will do, but Zalacca fruit is mixed with it … Kelantan Malays have faith in a mouthful of dry earth eaten immediately on receipt of the injury’ (Burkill 1935). Interestingly, Zalacca fruit peel (which is a waste product, left over from its culinary use) can adsorb copper ions, with potential for use as a detoxicant for industrial waste (Sirilamduan 2011). (Image courtesy Wikimedia Commons CC-by-SA 3.0 Unported)

Animal Geophagy

Zalacca edulis (Salacca zalacca) from Berthe Hoola van Nooten, Fleurs, Fruits et Feuillages Choisis de l’Ile de Java, 1863–64. Pieter Depannemaeker (lithographer), Lederberg, Ghent.

Many animals eat earth and are quite selective about the type of soil they consume. Birds and chimpanzees have been the most common subjects for study. In Borneo Red-leaf Monkeys (Presbytis rubicunda), and in Tanzania Chimpanzees (Pan troglodytes), are known to partake of termite mounds as part of their diet – while in Peru, Moustached Tamarins (Saguinus mystax) utilise the mounds of leaf-cutting ants. These resources would contain diverse minerals, notably iron and potassium, as well as some magnesium, phosphorus and calcium. There are other sites, known as ‘licks’, that are salt-rich, providing a source of sodium that is not readily available elsewhere. Plants are often a poor dietary sodium resource, so good alternatives are readily exploited. The African Buffalo (Syncerus caffer caffer) and the Mountain Gorilla (Gorilla beringei beringei) seem to have a preference for iron-enriched clay resources. The fact that soil may act as a detoxicant for

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The Malays believed that tigers and elephants ate earth for its medicinal qualities. Indeed, the practice could become so well established in elephants as to be considered an aberration. Sir George Maxwell’s translation of Mantra Gajah included the following antidote: ‘it is directed that to break elephants from the habit, baked earth worms should be mixed with black earth and this given to them’. (Image courtesy Chris Crosland & Jenny Shepherd) Vervet Monkey (Chlorocebus pygerythrus), in the Krugersdorp Safari Reserve, South Africa.

harmful plant chemicals could well be a motivating factor behind its use by numerous animals – notably apes, lemurs, monkeys and various birds. In addition, the antacid and antidiarrhoeal properties of kaolin-based clays would be familiar to some species (Abrahams 2005). Doubtless, similar to humans, different animals in different regions have their own favourite supplies. Certainly, African and Asian elephants have a preference for some clay sites over others (Limpitlaw 2010). A Sri Lankan study found that soils eaten by elephants were richer in kaolinite and illite in comparison to non-geophagic soils, which contained higher amounts of smectite. It was suggested that the elephants ate the soil, not as a mineral supplement, but as a detoxicant to deal with unpalatable dietary components (Chandrajith 2009).

Early last century Walter Roth observed that in Australia: White clay, a kaolin (hydrous silicate of alumina), is eaten, both at the Bloomfield and at Cooktown in northern Queensland. In the former district, it is generally … dug out from the veins in the cliffs or in the banks of the creeks, and then carefully pounded and sifted, so as to render it quite smooth and free from grit. It is next placed in a bark trough, and, by the addition of water, worked into a stiff paste. This paste is now made into a cake … and placed in the sun for from six to eight days, when it is eventually wrapped up in leaves, buried in the ashes, and a hot fire made over it. When cool, it is ready for use and considered a delicacy. Clay from the ant-hills (outside covering) was also part of the diet at Bloomfield: ‘used to “fill up” with’ when no other edible substance is available. The women and piccaninnies seem always able to eat of this, even after a meal of things more nourishing: it requires no preparation, and is known as kappi (Roth 1901).

Similar uses of clay were recorded from the Northern Territory (Barr 1988; Bateson & Lebroy 1978). On

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Groote Eylandt a white riverine-sourced clay was sometimes eaten by Aboriginal women if they were hungry (it was said to taste like fish), although it was not eaten by the men. The clay was also considered to be a useful anti-diarrhoeal agent and could be taken by pregnant women to ‘make their stomach cool’ – albeit said to cause constipation if too much was eaten (Levitt 1981). The reference to the constipating effect is of interest. The absorption capacity of the intestine can be compromised by excessive clay ingestion, resulting in abdominal discomfort. X-ray studies have clearly shown that clay balls can form in the intestine. Their presence can be highly problematic if they result in intestinal obstruction – a very painful and distressing situation. In severe instances, perforation of the bowel has occurred (Abrahams 2002; Ginaldi 1988; Bateson & Lebroy 1978).

Strange Desires

The term ‘pica’ has been used to describe the unusual cravings of pregnant women who eat dirt – a somewhat off-key habit that has generally been tolerated, and regarded as a temporary aberration. However, in medical circles pica can refer to any abnormal craving, such as eating paper, rubber, chalk and numerous other odd items – some of which can be quite incompatible with dietary requirements. Medical opinion has, overall, considered dirt-eating to be quite abnormal – and it has sometimes been equated with serious mental instability. This opinion is, rather dramatically, reflected in the writings of Avicenna (around AD 1000) who even called for the control of it ‘in boys by use of the whip, in older patients by restraints, prison and medical exhibits, while incorrigible ones are abandoned to the grave’ (cited in Halsted 1968). A serious misdemeanour indeed. While the habit has often been associated with mental disorders, whether geophagy itself actually falls into that category continues to be a matter for debate. Geophagy has endured over the ages. Many cultures have utilised earth and clay in the diet and may well have derived various mineral supplements from the practice.

This display in the Glore Psychiatric Museum, Saint Joseph, Missouri, shows the stomach contents of a former inmate – demonstrating the bizarre nature of some psychiatric problems. The patient swallowed over 1,446 items, which included 453 nails and 42 screws – as well as safety pins, spoon tops, salt and pepper shaker tops. She did not survive surgery to remove the offending objects.

Mineral Matters

There have been numerous studies that show interesting variations in the mineral content of edible forms of clay.9 These investigations provide an indication of the differences in clay samples sourced from different geological regions – and there is always an exception to general expectations. For instance, while most clays are salt-free, the use of ‘salty clay’ has been recorded in South America and salt-enriched earth in India (Abrahams & Parsons 1996): Africa, Zanzibar (Pemba Island): levels were • insignificant for phosphorus (0.00–0.09%), sodium (0.00–0.76%), manganese (0.00–0.04%), and fairly low for calcium 0.04–2.97%), magnesium (0.13–1.16%) and potassium (0.06–2.12%); iron levels were higher (0.46–5.74%). Zinc could also be present (4–44 ppm) (Young 2010a). • Africa: clays sourced from Gabon, Kenya, Nigeria, Togo, Zambia and Zaire showed substantial variability and were generally low in phosphorus (175–349 mcg/g). The difference in other mineral levels could be significant: calcium (143–4145 mcg/g), magnesium (603–1628 mcg/gm), zinc 9 The overall lowest–highest mineral levels are noted for these studies. However, greater detail regarding individual clay types and more complete mineral analysis is available in the original papers. (See also Abrahams 2005; Tateo & Summa 2007.)

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(12–185 mcg/g), manganese (155–3408 mcg/g). Some samples had a particularly high iron content (11.6–60.0 mg/g[sic]) (Johns & Duquette 1991). • USA: Californian clay minerals were found to be similar to some African samples: calcium (4217 mcg/g), phosphorus (393 mcg/g), magnesium (3980 mcg/g) manganese (3980 mcg/g), as well as being high in iron (39.3 mg/g[sic]) (Johns & Duquette 1991) • Sardinia: low phosphorus (131–436 mcg/g) and manganese (38–86 mcg/g), with higher levels of calcium (3788–5718 mcg/g), magnesium (5608– 8924 mcg/g) and zinc (57–110 mcg/g). Iron values (34.1–51.6 mg/g) were high (Johns & Duguette 1991). Certainly this indicates that there is substantial potential for differences in the effects associated with the use of clay in the diet. Studies from Australia have shown a similar amount of variability in clay mineralogy, including clay sourced from termite mounds, which is quite a popular resource in many countries where geophagy is practised. (Below) Edible clay is often found around riverine sites – as are coloured clay ‘stones’, which are of a soft consistency. In northern Queensland, edible clay deposits have been sourced from the Bloomfield River (shown here), Saltwater River (near Pollock’s Crossing) and Barrats Creek (gumbura clay) – as well as the Daintree River, where a soft stone, ‘like a talc’, was found in many colour forms: purple, pink, yellow, white, brown and red. These different clays contain a variety of trace elements (Rowland 2002).

Ochre rocks are often found in streams. Daintree National Park

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Table 6.1 White Clay and Termitaria Samples from the Northern Territory

Investigations evaluating the mineral content of clay have unearthed some interesting support for its use. Samples were shown to contain the following concentration of calcium, magnesium, iron, potassium, and sodium (mg/100 g): Clay type

Ca

Mg

Fe

K

Na

Termitaria: soil 10 cm inside mound (Barr 1993)

10–11 mg

27–38 mg

780–4341 mg

71–95 mg

3.1–3.2 mg

Termitaria: mound casing (Barr 1993)

104–166 mg

113–156 mg

1327–2217 mg

139–166 mg

4.8–5.8 mg

393 mg

15 mg

572 mg

3798 mg

0.12–0.14%

1.0%

0.38%

0.09%

White kaolin clay from Yirrkala 119 mg (Barr 1993) Groote Eylandt: silicate clay (Levitt 1981)*

aluminium —

* Analysis by Groote Mining Company (mineral oxide %): silica (SiO 66.6%) and aluminium (AlO 24.5%), additional minerals present in small amounts included strontium (SrO 0.03%), barium (BaO 0.14%), titanium (TiO 0.63%) and phosphorus (0.34%) (Levitt 1981).

Table 6.2 Summary of Australian Clay Resources Utilised by Aboriginal People See Rowland (2002) for a more detailed discussion. Northern Territory: Groote Eylandt Northern Territory: Groote Eylandt Northern Territory

Red or yellow clay (malarra) Termite mound clay (ebinga) White clay (duingira)

Clay: eaten for mineral deficiencies (Levitt 1981)

White clay (Benamanrkagunara, White Clay Dreaming)

Clay: highly prized and used for gastrointestinal disorders and diarrhoea (Eastwell 1979; ) White clay (kaolin): baked in fire, like a damper, then made into pellets or powder (1 teaspoon) mixed with water and taken for diarrhoea (Barr 1988). White clay: ‘used as a medicine to cure stomach aches and diarrhoea. And to “settle the stomach” when it is upset … also taken to “line the stomach” before eating yams or fish which may be poisonous’. Clay eaten to allay hunger and for hookworm infestation (Bateson & Lebroy 1978) Clay from termite mound (Arnhem Land): gastrointestinal disorders (Eastwell 1979). Termitaria: gastrointestinal problems; eaten by pregnant women (Foti 1994; Barr 1993, 1988). Ant-hill earth extract (boiled in water) used for stomach aches and diarrhoea (Bateson & Lebroy 1978). Clay: eaten, drunk in solution, rubbed over body: cure for internal pain, headache, joint pain, eye complaints, snake-bite wounds; increases flow of breast milk (white clay) (Memmott 1979). Clay: kneaded into balls, rolled in banana leaves and roasted: eaten by pregnant women to ensure birth of a fair-skinned child. Children ate clay to make them ‘stronger, braver, sturdier’ (Alfred Cort Haddon, cited in Rowland 2002). Riverine clay: sieved to remove all coarse particles. Refined clay put in trough, mixed with water to make a dough. This was kneaded to make long flat cakes that were sundried (6–8 days). Cakes then roasted in earth oven: wrapped in leaves, buried in ashes and fire lit above them. When cooled they were considered a great delicacy (Anell & Langercrantz 1958). Large clay or mud pills: 1–2 taken for diarrhoea (Roth 1897).

Northern Territory

Termite mound (anthill earth; termitaria)

Mornington Island

White clay

Torres Straits, Murray (Mer) Clay: ‘greasy chocolate-like Island earth’

Queensland (northern): Bloomfield

White kaolin clay

Queensland: northwest and central regions

Clay

Clay: anti-diarrhoeal (Levitt 1981)

A DESIRE FOR DIRT? Queensland: Cape York

White clay

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Clay: white (kaolin) clay from the beach mixed with water, washed and strained, used as a treatment for coughing or tuberculosis; clay also eaten as an anti-diarrhoeal agent (Isaacs 1987). Fire-roasted clay mixed with water and a teaspoon taken as an antidiarrhoeal agent (Barr 1993).

Queensland (northern): Clay Evelyn Tableland Queensland: Taroom Soft white stone (copi)

Clay: eaten as an abortive and contraceptive (Mjoberg 1918).

Western Australia

Red clay (wilgi) White pipeclay

Clay heated and mixed with emu oil, applied on a dressing (paperbark, gumleaf or wad of possum fur) to wounds. Clay also applied to sore eyes (Hammond 1980).

Western Australia

Broolga (red earth)

Clay eaten for stomach trouble (White 1985).

Clay heated and made into a fine powder (resembling cornflour), mixed with water: used for a variety of ailments (L’Oste-Brown & Godwin 1995).

In Australia red-brown termite mounds have been commonly used as a supplement by Aboriginal women during pregnancy and following delivery. The earth was regarded as having tonic attributes – as well as being useful for easing abdominal pain and to promote lactation. It was taken by young girls to ease period pain, and widely used as an absorbent antidiarrhoeal remedy (Barr 1993, 1988). Dulcie Levitt (1981) comments: ‘clay from termite mounds was usually eaten by women who had been inland for some time, living on roots and wild honey. It was probably eaten to cure mineral deficiency. Clay processed by animals was considered to be safer than other kinds. The clay was crumbled in the hand to a powder, which was dropped into the mouth. The clay termite tunnels in logs were also eaten’.

Mangrove worms (Teredo novalis). Coastal Aboriginal tribes can utilise a substantial range of marine resources as food. Among them are Mangrove worms, which may provide another incidental source of dirt in the diet. Bateson and Lebroy (1978) commented: ‘Another source of ingested clay may be the mangrove worms eaten by Tiwi people. These worms inhabit the mud around the roots of mangrove trees. These worms are swallowed whole after their intestinal contents have been expressed, but it is highly likely that some mud will remain and so be present in the alimentary tract of the consumers.’ Not only are these worms harvested wild by Australian Aboriginal people, but in parts of Southeast Asia they are considered a delicacy. (Upper image courtesy Coleen P Sucgang, Poseidon Sciences; lower image courtesy Rita Albert, www.flickr.com/photos/rietje/4631747412)

Two different types of clay have been used to build these termite mounds, which have been decorated with images of the kangaroo and emu (‘bush graffiti’). Clays that have a reddish colour tend towards a higher iron content. (The ecological role of termite mounds is discussed in Chapter 7.)

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In cases of dietary deficiency, some minerals can take on greater importance than would be normally expected. Certainly, magnesium is known to have significant antispasmodic properties – although the question of mineral bioavailability is an important issue that does not appear to have been reliably solved with regard to geophagic habits. In general, the levels of most minerals found in termite nest soils (red-brown, yellow, grey earths) are not very high, although iron and sodium can be an exception. Some types are even considered to enable a measure of electrolyte replacement (Barr 1993) – although this would depend on the mineral composition and exchangeable ion qualities of the earth ingested. Mineral levels were consistently higher in the covering of the mound than from soil within the mound, which means that Aboriginal people’s selection of pieces of the outer casing (from newly built sections) was a wise choice. The earth was either crushed and eaten on its own, or larger pieces (palm-sized) were ground into a powder and mixed with around a litre of liquid (water, milk, tea) to make a fine suspension. Sometimes the casing was burnt before grinding, at other times a particular mound could be preferred, such as those found at the base of Eucalyptus tectifica. In some places honey ants (Melophorus spp.) were even added to the mixture (Barr 1993, 1988). The use of termite nests and termites for food was mentioned by the German anthropologist Berthold Laufer (1930):

White-ants’ nests constructed of soft, fine earth, generally of a reddish black color, are consumed in India in the same manner as in Africa. Coolies of Assam are disposed toward white-ant soil taken from the center of the nest, white ants themselves being included as a delicacy … Among the mountain tribes of Travancore the men, not the women, eat this earth with the ants inside the cells, sometimes adding honey to it. It is taken, not in small medicinal doses, but in rather large quantities. No evil effects have been noticed to follow its use ... Steatite or soapstone ground to powder and mixed with flour has served in India as a regular famine food, in the same manner as in China.

In some Indian traditions termites (Odontotermes formosanus) were eaten to enhance lactation and studies have suggested that they are a good proteinrich dietary resource (560 calories/100 g), superior to steak (322 calories/100 g). They contain a high fat component for an insect (around 600–760 kcal/100 g) – as well as carbohydrate, a range of essential amino acids and, depending on the species, good amounts of various minerals (Solavan 2006).

Termites and Spinifex

Spinifex triodia, Finke Gorge National Park. (Courtesy Craig Nieminski, flickr)

Mud wasp at nest. Occasionally mud wasp nests have been utilised as a source of geophagic clay, such as those of the mud-daubing wasps (genus Synagris) from Sierra Leone, albeit not a common practice (Abrahams 2005).

Termite mounds found near clumps of Spinifex grass (Triodia pungens) incorporate this resinyielding plant into the mound, which makes an effective aromatic repellent when burnt – and explains its use as a mosquito repellent (Lindsay 2001). The smoke is thought to have healing properties for sick babies – and ‘smoking’ (or fumigation) is a traditional treatment for diverse forms of illness (Barr 1988). This is an interesting concept, about which Professor John Pearn (2005) comments:

A DESIRE FOR DIRT? The smoking of infants has deep ritual significance and is still widely used. Aboriginal peoples in many communities today believe that the smoking of infants has important pro-active protective medical overtones. There is a fundamental and deeply held implication also that the smoking rituals will have long-term effects and make babies strong and placid. The smoking of infants is undertaken by mothers and grandmothers, often as an unhurried and enjoyable practical ceremony conducted within the fellowship of a small women’s kinship group. A fire-pit is dug, a fire lit and hot coals prepared. Pieces of resinous termite mound are added to the hot coals. The resinous material which is used for infant-smoking is specific for different communities. In some communities ofthe Ngarinyman and in those of the Warlpiri, termite mounds are found particularly amongst clumps of the Spinifex Grass, Triodia pungens. Leafy green branches are then placed on top of the glowing coals in the fire-pit. When there is a continuous flow of smoke, and in the absence of any flame, the baby is held lovingly above the leaves, and is invested by the smoke. The smoking continues until the fire-base cools. In the smoking of babies, leaves from any one of several species are used by communities in Central Australia. These include: Acacia aneura, Acacia lysiphloia, Eulalia aurea, Exocarpos latifolius, and Dodonaea viscosa. It is interesting that these five species contain little or no essential oils, but generally contain triterpenes and higher than average concentrations of tannins (6 per cent of dry weight in the case of Exocarpos) and saponins.

In addition, termite mound pieces were added to meals cooked in an earth oven to impart a distinctive ‘smoky’ flavour to meats such as turtle, fish or kangaroo. Furthermore, termite eggs and larvae are considered to possess useful healing effects, and have been used as a liniment (Low 1991; Barr 1988). This could possibly be due to the fact that termites are oil-rich insects – which have been used in Africa and some parts of Asia as a dietary resource. In the Northern Territory a post-natal remedy was prepared from a clump of Spinifex, crushed with a little dark-coloured termite mound and warmed on a bed of coals to extract a soft dark resin. The mix is crushed, sometimes a small amount of water added,

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and the resultant liquid used by a mother after childbirth. Small sips could be given to the baby to promote good health and ensure its strength. The grass decoction could also be recommended as a body wash for treating colds and influenza. Another Spinifex, Triodia microstachya, has been utilised as a decongestant decoction for treating influenza, coughs and respiratory congestion. It is considered to be a powerful medicine that has been widely used in preference to ‘clinic medicine’ (conventional drugs). It is also useful for skin infections and scabies (Wightman 1994, 1991; Barr 1993; Smith 1993).

Spinifex hummock grasslands at Karijini National Park, Western Australia. The green hummocks are Triodia pungens (Soft Spinifex); the blue-grey hummocks are Triodia basedowii (Hard Spinifex or Lobed Spinifex). The trees in the background are Eucalyptus and Acacia species. (Image PW Hattersley, in L Watson & MJ Dallwitz (eds), The Grass Genera of the World, 1992, CAB International, Wallingford, UK)

The Downside of Clay Ingestion

The detoxicant properties of clay can benefit digestion by binding with toxic substances present in the bowel, thereby having a cleansing effect. This is due to a very small particle size (<2.0 μm) that results in a vast surface area (hundreds of square metres per gram of clay) with a high concentration of ions and compounds located on the surface. This gives the clay an extraordinary adsorptive (binding) property (Haydel 2008). However, the binding effect on minerals may not always be beneficial, suggesting overindulgence should be avoided.

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Natural crystalline zincite (zinc oxide). (Courtesy JA Davidson, Wikimedia Commons, Public Domain)

One study has shown that zinc deficiency (hypozincaemia) was common among Aboriginal communities in the Kimberley area (Western Australia), and this was linked to the practice of geophagy.10 There were, however, a number of complicating factors that included intestinal parasites, the use of unleavened bread (contains phytic acid), poor dietary habits (high levels of refined foods and sugar) and mineral losses in sweat (Cheek 1982, 1981; Holt 1980). All these factors can seriously compromise zinc levels. The absorption of zinc can be reduced by a high cereal diet, where zinc forms an insoluble zinc-calcium-phytate complex, thereby limiting its bioavailability. Intestinal parasites can cause bleeding into the bowel or mineral malabsorption. Excessive perspiration is a perennial hazard of the tropical summer that is usually not dealt with effectively by rehydration drinks, many of which lack an absorbable mineral component (Antia 1989; Halsted 1968). Zinc deficiency can have exceptionally tragic consequences for children. In the 1950s and 1960s geophagy causing zinc deficiency was recorded in Iran, Egypt, Turkey, Portugal, Panama and Puerto Rico. It was linked to serious developmental abnormalities such as growth retardation (dwarfism), sexual immaturity (delayed puberty; hypogonadism) and impaired intelligence – as well as skin lesions, poor wound healing, immune system depression, loss of taste and desire to eat, anaemia and enlargement of the liver and spleen (Cavdar 1980; Arcasoy 1978; 10 This study also showed a higher incidence of low iron levels (hypoferraemia) and excess copper (hypercupraemia)

Aboriginal stockman, Central Australia, photograph by Axel Poignant, ca. 1947. The old and weathered soils on the Australian continent are likely to be deficient in various minerals. Indeed, in many regions of Australia the soils are zinc deficient, which will influence the quality of any crops grown. As a result ‘the vegetation is not likely to be rich in the trace mineral’ – and this can seriously influence compromise dietary zinc intake (Cheek 1981). (nla.pic-an13388178-v)

Halsted 1968; Prasad 1963a, 1963b; Halsted & Prasad 1960). These problems persist in some cultures to this day. Indeed, relatively recently young Iranian men who practised clay-eating were found to suffer from zinc deficiency (Lamson 2006). It is an interesting observation that zinc supplementation in deficiency conditions has been noted to stop the geophagic habit – and, vice versa, a deficiency of zinc has resulted in odd food cravings (including earth eating) due to the development of abnormal taste perceptions (Tateo & Summa 2007). Iron deficiency anaemia has long been associated with geophagy – a condition that was familiar to Avicenna (980–1037 AD). Over a century ago it was also observed in India: ‘clay is eaten by people already anaemic, and the more they eat it the more anaemic they become’ (Hooper & Mann 1906). In northern Queensland, similar observations were recorded in 1892. Dr W Bacot, Resident Surgeon at Townsville Hospital, mentioned a couple of cases, primarily from Cairns: ‘a number of children … had been attacked by a sickness, the principal characteristics of which were an inordinate appetite for earth (especially a red clay, which was stated from its alleged sweet taste to be attractive to the children), with extreme anaemia and a distended belly. Several of these children died, and death was attributed to the poisonous nature of the soil, which was stated to have been found in large quantities in the intestines after death.’ His descriptions illustrate the compulsive nature of the disorder: ‘his mother noticed him eating black

A DESIRE FOR DIRT?

271 Portrait of an Aboriginal infant, Central Australia, ca. 1920, John Newlands. Part of the collection ‘Album recording an inspection of the proposed Darwin to Adelaide railway route by Federal Public Works Committee, 1920–1921’. (nla.pic-an23208348-v)

Sepiolite. In Turkey, iron-deficiency anaemia has been linked to clay consumption, notably clay characterised by sepiolite (magnesium trisilicate) and montmorillonite (bentonite) (Abrahams 2005). (See Table 5.1, Chapter 5). (Image courtesy www.mineraly.sk, Wikimedia Commons, CC-by-SA 3.0 Unported)

sand. From this time he began to rapidly lose his colour, strength and appetite, and was always whining. His limbs became very thin, while his belly increased in size with pain and constipation, his stools being largely composed of sand … [his mother] to prevent him eating sand, confined him to the house, with the result that he ate the dirt he scraped from his parents’ boots, the walls and floor-board crevices … He is now extremely anaemic; is thin and flabby, and has a large belly.’ Another child had similar symptoms: ‘she began to lose colour, her appetite, and her spirits, becoming thin and always complained to feeling tired; suffered from pains in the head and belly, which latter was much distended … she was observed eating red clay; and when kept indoors, she swallowed wood ashes and the dirt she scraped from the floor’. Later she was found eating the dry sunbaked sand around her home and would not be deterred. She died six months later (Bacot 1892). A couple of types of worm infestation were associated with the condition, notably whipworm and hookworm. Bacot concluded: Whether the earth-eating was the cause or effect of the presence of these worms is not so clear perhaps. I am not aware the earth-eating is usual in persons infested by these parasites, but from the facts that the earth-eating was in most cases preceded by failing health, and that when circumstances prevented the children getting earth, they ate the dry, bleached, tasteless sand, it appears that the attractive flavour attributed to the red soil has nothing to do with it, and that it is the result of some other cause,

probably the irritation from the presence of the parasites in the intestines.

The complications from mineral imbalances may well have been an important contributory factor. The type of earth utilised can have different adsorbent and mineral release properties. A case history of geophagia involving the consumption of black dirt (garden earth) by an African woman is illustrative of this. On admission to hospital the woman was found to have iron-deficiency anaemia – as well as experiencing limb paralysis and low serum potassium levels (hypokalaemia) of 1.3 mmol/L (normal range 3.5–5.0) (Dreyer 2004). Analysis showed that the effect of the black earth differed in some respects to that of an edible red clay sourced from the local market, which would influence mineral bioavailability in the gastrointestinal tract: • Red earth (clay-like): slight absorption of potassium. Iron was liberated at pH 2.0 and absorbed at pH 6.2. • Black earth (pH 2.0 and 6.2): absorbed sodium, potassium and iron. It liberated calcium and magnesium – the latter in quite large amounts. A complex mineral interaction was associated with the use of the black earth. Although the woman’s dietary intake of magnesium was found to exceed the RDA (recommended daily allowance), her serum magnesium concentration was normal. Her intake of sodium was low and that of calcium was below the RDA – although serum levels were found to be normal for both minerals. Iron intake was also deficient. It was concluded that the adsorbent effect of the earth on potassium and iron could result in clinical symptoms of hypokalaemia (low potassium)

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and anaemia, respectively. It was, however, possible that the liberated calcium could provide a level of dietary supplementation. In addition, while iron from the red clay may have had limited bioavailability, that from the black earth did not (Dreyer 2004). This report is interesting because exactly the same symptoms have been recorded in the older literature. In 1964 an American report by Mengel and colleagues described a case of iron-deficiency anaemia and hypokalaemia in an African-American woman who was admitted to hospital. She was in the habit of eating clay with each meal, which was directly linked to the development of her condition. Another case of hypokalaemia in an African woman in Cape Town was associated with myopathy (weakness of the left side of the body) and other symptoms demonstrating low potassium levels: photophobia, vomiting, and disturbances in kidney and liver biochemistry (McKenna 2006). Other authors have reported similar findings (Trivedi 2005; Abrahams & Parsons 1996; Severence 1988; Feldman 1986). Strangely enough there are also reports of hyperkalaemia in the literature, particularly in patients with chronic renal failure. This was linked to the geophagic use of potassium-enriched soils with high bioavailability of this mineral: ‘Since riverbed clay contains as much as 100 mEq11 of potassium in 100 gm of clay, much of which is exchangeable at acid pH, the mechanism of geophagia-induced hyperkalemia appears to be the absorption of potassium released from clay after ingestion’ (Gelfand 1975). 11 mEq refers to one thousandth (10−3) of a chemical equivalent.

A Matter of Bioavailability The most important beneficial minerals in geophagic clay are iron, magnesium, potassium and calcium. Their usefulness depends on their bioavailability and ion exchange is an important consideration in this regard (see also Table 5.1, Chapter 5). If the minerals are strongly bound within the clay, they will have a low availability for release, and vice versa. Lead, which merits particular concern, provides a good illustration. The ingestion of quite high levels of lead can occur when weathered soils are utilised – although because lead is usually present in a

Iron bands in a formation specimen from Upper Michigan. Bioavailability is an important concept with regard to mineral absorption from clay. Iron-rich clay that does not contain associated adsorptive minerals allows a greater level of iron to be absorbed during digestion. However, on occasions where soluble iron is already present in the gastrointestinal tract, it can be absorbed by some clay forms – resulting in an overall iron loss from the body (Tateo & Summa 2007). (Image courtesy Mark A Wilson, Department of Geology, College of Wooster, Ohio)

stable form (pyromorphite) with low solubility, this results in low bioavailability. However, because not all lead is bound in this manner, some soil types can involve a higher risk of exposure (Abrahams 2002). Bioavailability can be linked to a number of other considerations. Mineral absorption is strongly influenced by the digestive process, particularly pH levels. This changes during food transit from the acidity of the stomach (pH 1–2 fasting, pH 2–5 with food) to alkaline conditions in the intestine (higher pH in small intestine: duodenum 4–5.5, jejunum 5.5–7, ileum 7–7.5). The strongly acidic conditions of the stomach, which are due to hydrochloric acid secretion, permit cation exchange of minerals. This allows an increased solubility of iron oxide – the level of which can vary substantially, depending on the mineral composition of the clay involved. In the small intestine adsorption of minerals will occur due to increased pH levels. In general, smectite clay has much less bioavailability of iron in comparison to kaolin-based clay. Clay from Ghana and the ‘sacred earth’ (Tierra Santa) of Central America contain a large fraction of iron in bioavailable form (Abrahams 2005; Hunter & Kline 1984; Hunter 1973).

A DESIRE FOR DIRT?

Clays sourced from Bengal, known as sikor, contain calcium, copper and manganese in an absorbable form. While low bioavailability would prevent iron absorption, sikor can be eaten in quantities large enough to contribute a substantial amount of this mineral to the diet. The absorption of potassium and lead was similarly low – although concerns have been expressed with regard to the ingestion of potentially toxic amounts of the latter. Lead exposure has been linked to lung cancer, adverse effects on the immune system, neurotoxicity and developmental problems, particularly in children12 (Al-Rmalli 2010; Abrahams 2006). 12 See also ‘Lead Poisoning’, Chapter 5.

Clays that are rich in kaolinite (kaolin group) or smectite (bentonite) are most commonly utilised in geophagy. The high level of iron present in smectitebased soils is not bioavailable, while that in kaolinbased samples usually is. This would certainly help to explain some of the variability in iron absorption from soil samples. Indeed, research has shown anaemia can result where soils actively prevent dietary iron absorption13 (Young 2010b; Mahaney 2000; Minnich 1968). Other studies, however, of women in Texas and Mississippi did not demonstrate this relationship – which suggests iron bioavailability is a key issue. Other considerations include dietary items such as tannin and cereal phytates, which inhibit iron absorption, while foods such as meat and fish enhance absorption. Vitamin C has a significant enhancement effect with regard to iron (Harvey 2000). Interestingly, South African studies of iron absorption from beer have shown that iron is highly bioavailable from this source, with an intake of up to 50–100 mg being recorded from locally brewed beer (Charlton 1973). The tonic reputation of dark beers such as stout and Guinness may well be linked to a bioavailable iron and B vitamin content. 13 The RDA for iron is around 8 mg, with significantly higher levels being required during pregnancy (27 mg/day) and menstruation (18 mg/day). However, it should be noted that iron can be difficult to absorb under the best of conditions for some people, particularly menstruating women. Iron is present in two forms: haem iron and non-haem iron. Haem iron from animal foods is, generally, relatively well absorbed – while the non-haem iron found in plants, soil and water supplies, is not. The latter includes forms of iron (i.e. ferric oxide and ferric hydroxide) that are present in the dust/soil involved in food contamination or in water leached from cooking pots. Even so, their solubility and reactive qualities with other compounds may vary significantly (Harvey 2000).

Cachexia Africana: A Complicated Clinical Picture The nineteenth-century literature mentions a condition known as Cachexia Africana, which was associated with the habit of geophagy. The French knew it as mal d’estomac (stomach sickness). In 1843 Dr John Imray described the condition: The symptoms of mal d’estomac are variable … change of temper and loss of spirits, dyspepsia, general debility, and depraved appetite for food. The substance usually preferred by the dirt eater is a soft clayey rock, having a spotted marly appearance and of a soapy taste; but any kind of dirt may be eaten … In the first stage of the disease, then, we have simply derangement of the functions of digestion and assimilation. As it progresses, symptoms of organic lesion set in. The patient at first usually complains of a fixed pain over the stomach or in the cardiac region, with palpitation of the heart, shortness of breath, and muscular debility. The mucous linings of the mouth and lips present a peculiar exsanguineous appearance, by which alone the existence of the disease may often be determined. The perspiration is suppressed, and the glossy jet of the healthy skin is changed for a lighter shade.

This was the disorder observed by David Livingstone on his travels in 1870: Safura is the name of the disease of clay or earth eating, at Zanzibar (coast of East Africa); it often affects slaves, and the clay is said to have a pleasant odour to the eaters, but it is not confined to slaves, nor do slaves eat in order to kill themselves; it is a diseased appetite, and rich men who have plenty to eat are often subject to it. The feet swell, flesh is lost, and the face looks haggard; the patient can scarcely walk for shortness of breath and weakness, and he continues eating till he dies. Here many slaves are now diseased with safura; the clay built in walls is preferred, and Manyuema women when pregnant often eat it. The cure is effected by drastic purges composed as follows: old vinegar of cocoa-trees is put into a large basin, and old slag red-hot cast into it, then ‘Moneyé’, asafoetida, half a rupee in weight, copperas, sulph. ditto: a small glass

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary of this, fasting morning and evening, produces vomiting and purging of black dejections [sic], this is continued for seven days; no meat is to be eaten, but only old rice or dura and water; a fowl in course of time: no fish, butter, eggs, or beef for two years on pain of death. Mohamad’s father had skill in the cure, and the above is his prescription. Safura is thus a disease per se; it is common in Manyuema, and makes me in a measure content to wait for my medicines; from the description, inspissated bile seems to be the agent of blocking up the gall-duct and duodenum and the clay or earth may be nature trying to clear it away: the clay appears unchanged in the stools, and in large quantity. A Banyamwezi carrier, who bore an enormous load of copper, is now by safura scarcely able to walk; he took it at Lualaba [a river near Lake Tanganyika] where food is abundant, and he is contented with his lot. Squeeze a finger-nail, and if no blood appears beneath it, safura is the cause of the bloodlessness.

In general, clay eating was used as a remedy to alleviate intestinal distress – a habit that was maintained by African slaves shipped to the Americas. It probably added to their already compromised nutritional state, even though they may well have gained some temporary relief from its use. At times slaves were reported to use geophagy as a form of suicide. It appears that the desperate would eat soil to excess – believing that when they died their spirit would return to their homeland. Over time this belief was taken up by so many of the interred slaves that it reached epidemic proportions. In Jamaica, in 1687, the condition was said to be responsible for over half of the slave deaths. Their ‘owners’, who were not too impressed with the situation, came up with some rather drastic and quite inhumane deterrents: iron gags, face masks, and chaining the offenders to floor planks. Even after death they were not safe from their master’s ire and their bodies were dismembered – a harsh fate, for it would not allow them to return to their spiritual home. Unsurprisingly, the geophagic tradition eventually lost popularity (Abrahams & Parsons 1996). While the description of Cachexia Africana would certainly suggest geophagic origins, there are a number of other wasting (or cachexic)

conditions with similar symptoms (sluggishness, mental insensibility, lassitude and profound muscular weakness) that could easily complicate the clinical picture. They include tuberculosis, and nutritional deficiencies such as pellagra (B3, niacin deficiency) and beriberi (B1, thiamin deficiency). Furthermore, the cachexic condition could easily be compounded by parasitic infections such as bilharziasis (Schistosoma fluke), sleeping sickness (Trypanosoma parasites), kala-azar (Leishmania infection) or hookworm (Ancylostoma duodenale and Necator americanus) (Abraham & Parsons 1996).

Slave funeral at a plantation in Suriname. Lithograph by Theodore Bray, 1818–1887. (Courtesy Tropenmuseum of the Royal Tropical Institute, Amsterdam)

Arab slave traders and their captives along the Ruvuma (Rovuma) river, Tanzania and Mozambique, 1866, artist unknown.

A DESIRE FOR DIRT?

Parasites from Poo

Children experiment with eating all forms of dirt, although they usually ‘grow out of it’ by around 3–4 years of age. In particular, the helminths (‘worms’) responsible for ascariasis (Ascaris lumbricoides) that infect schoolchildren all over the world appear to be linked to the habit.14 Pregnant women risk similar exposure from geophagy. In many traditions the clay is processed (washed and filtered) and/or baked before use, which tends to limit parasite contamination – although the efficacy of heat exposure on eliminating contaminant microbes in clay has yet to be fully established.15 While viable geohelminth eggs are likely to be removed, some other microorganisms are not so easily eliminated. Experiments with heat exposure of bentonite found that while most bacteria were destroyed, some spore-forming species persisted. Furthermore, processing may reduce the therapeutic value of the clay – with a potentially significant depletion in trace elements (Bisi-Johnson 2010; Mascolo 1999). A study of Tanzanian women who ate clay during pregnancy showed a strong link to ascariasis parasites, but not hookworm or trichuriasis. Their soil consumption could result in the development of anaemia, which could be severe (Kawai 2009). Another study of Kenyan women showed a similar association with ascariasis and, although the links with hookworm and trichuriasis were less clear, those who ate termite mound earth had a higher prevalence of ascariasis and hookworm parasites (Luoba 2005). A survey of South African schoolchildren likewise found a high association of ascariasis with termite soil, although it was lower in those eating tree-termite soil, as distinct from soil sourced from termite mounds (Saathoff 2002). Interestingly, re-infection is the key to the parasite’s persistence in the environment. The worm cannot replicate within a human, therefore reexposure is required to maintain the infection beyond two years (Callahan 2003). Human habits would appear to have a significant 14 Worldwide it is estimated that around 3.5 billion infections (possibly more) occur with parasitic geohelminths (Ascaris, Trichuris and hookworm) (Bisi-Johnson 2010). Ascarid worms are prevalent, possibly infecting around 25% of the world’s population (over 1.25 billion individuals) (Callahan 2003). 15 An analysis of white clay samples from Ghana identified various pathogenic bacteria including species of Alcaligenes, Staphylococcus and Candida. However, the samples did not have a high moisture content which would limit the level of bacterial contamination (Tano-Debrah & BruceBaden 2010).

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influence on the persistence of geohelminth infections. The fact that termite mounds have often been used as ‘screens’ for toiletry purposes can result in exposed contaminated faecal material being left in the environment – and thus easily accessible to domestic animals and wildlife. This can expand the site’s potential as a parasitic hazard. Ascaris eggs, which tend to be prevalent, adhere to soil particles. They are more resilient than Trichuris eggs (which are fairly easily destroyed), and this may account for the higher degree of Ascaris contamination (Luoba 2005; Abrahams & Parsons 1996). Hookworm is carried in dog and cat faeces. The Hookworm larva enters through the skin (usually the soles of the feet). Hookworm infection, which is a major cause of anaemia, can have some nasty consequences for children and pregnant women, including foetal damage that results in retardation of intellectual, cognitive and growth functions. The constant gastrointestinal distress associated with this infection also provides the motivation for those seeking an anti-dyspeptic remedy to indulge in geophagy. This can complicate the anaemia, compound pre-existing metabolic imbalances, and pose further risks for parasitic infection. In addition, because hookworm does not respond well to treatment, individuals can continue to spread the infection despite conventional antiparasitic medication, as well as being exposed to the associated risk of side-effects of drug therapy (Luoba 2005; Abrahams & Parsons 1996). Toxocariasis is another parasitic disorder that is associated with faecal contamination – this time from worms found in dog and cat excreta: Toxocara canis and T. cati respectively. The eggs from this parasite can survive in the soil for years. Infection is primarily associated with arthritic pain – with additional distress occurring with migration of the larva to the eye, viscera, lung, liver and spleen. However, not everyone will experience significant illness, with some individuals acquiring a level of immunity from exposure. Chronic low-level contact to the soil-borne tetanus bacteria has been similarly linked to a natural development of immunity (Brand 2009; Callahan 2003; Abrahams 2002). In addition, some more uncommon parasites can be found lurking in dirt, such as the American racoon roundworm (Baylisascaris procyonis) – which can cause severe neurological damage (Callahan 2003).

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Ascaris worm, female adult. (Courtesy CDC Division of Parasitic Diseases)

Canine Whipworm (Trichuris vulpis). There are canine and feline forms of Whipworm, albeit the latter is relatively rare. Infections are characterised by symptoms of diarrhoea, anaemia and dehydration. Fortunately these types of intestinal parasites rarely infect people. (Image courtesy CDC)

Trichuris sp. (Courtesy Roberto J Galindo, Wikimedia, Creative Commons Attribution)

Embryonated Hookworm egg – either Ancylostoma duodenale or Necator americanus, which are indistinguishable at this stage of development. There are three types of hookworm that can infect humans. Ancylostoma duodenale and Necator americanus are the two most common species, while Ancylostoma ceylanicum is rarely encountered (Abrahams 2002). Hookworm infection due to Ancylostoma duodenale is present in many Australian Aboriginal communities. The parasite, which burrows into the skin, has commonly been associated with iron deficiency and anaemia, particularly in children (Hopkins 1997). (Image courtesy CDC)

Left: Canine Roundworm egg (Toxocara canis); right: canine Hookworm egg found in the faecal sample of a dog. (Images courtesy Joel Mills)

Canine Hookworm (Ancylostoma caninum) attached to the intestinal mucosa. (Image source CDC Public Health Image Library)

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eil’s Disease: A Particularly Nasty W Tropical Bacterium

blindness), meningitis and heart inflammation (myocarditis, endocarditis). Fatalities can result from severe cases. Treatment options (a selection of antibiotics) have limited efficacy, and the condition is easily misdiagnosed. Blood tests need to be done within a week to confirm the diagnosis. Leptospirosis can be mistaken for a severe flu, numerous types of fevers (including typhoid, dengue and malaria), hepatitis or viral meningitis. The condition can be prone to relapse, with consequent severe symptoms. Much depends on the immune system response. Herbal medicines with immunosupportive properties can have an important role to play in limiting the complications of the disease. In Australia the highest incidence of the disease is in northern Queensland, notably around Ingham, Innisfail, Mossman and the Daintree.16

Sugarcane fields and banana plantations are environments where the risk of contamination by the Leptospira bacteria is very high for field workers.

In Australia and the Americas a debilitating bacterial soil-borne disorder called leptospirosis is a serious problem associated with waterinundated environments, including farmlands. It is transmitted (carried in the urinary tract) by wildlife (bandicoots, possums, kangaroos), rodents (native and imported) and farm animals (cows, pigs, sheep). The spirochaete (a thin filament-like motile type of bacteria), is problematic because it tends to persist in residual-water sites such as ditches and tyre tracks, which are common around farms during the wet season. Infection can easily occur via open wounds – resulting in severe fevers with copious sweating, headache, bone aches and gastrointestinal distress (vomiting, nausea, diarrhoea). Complications include kidney and liver failure, eye disorders (which can lead to

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Leptospira bacteria. (Courtesy Dr Martin Hicklin, CDC Public Health Image Library) 16 In the period 1991–2011 notification figures have varied between 108 and 245 per year, although 1999 was an exception with 320 cases reported (National Notifiable Diseases Surveillance System, April 2012). The condition is likely to be under-reported due to a lack of familiarity with the symptoms, difficulty in distinguishing it from similar feverish conditions, and the fact that definitive blood tests are not often requested within the required time. Many people would dismiss mild cases simply as a flu-like disorder and only seek medical advice if discomfort persisted, making the diagnosis difficult, if not impossible. Even individuals suffering relapses are unlikely to seek medical advice unless the symptoms are severe, due to the lack of treatment options.

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drug use (particularly antibiotics) and toxic chemical exposure (including pesticides, cleaning products) are other important factors. It appears that an ever-increasing number of people There is also the proposal that our environment has have developed immune reactions that are seriously progressively become unnaturally ‘clean’ (the hygiene out of balance with the very environment that hypothesis) – which has received serious consideration sustains us. Too few of us appreciate that we are from some researchers. This theory has been based on truly a ‘product of our environment’. Damage to the observations that young children exposed to less sterile immune response results not only from infectious living conditions experience a reduced incidence of disorders (viral, bacterial or fungal) – inappropriate ‘atopic’ disease. Disorders such as eczema, asthma and various allergic diseases are less evident in rural communities in the developed world, and in under-developed countries. This seems to be associated with contact with a wide range of parasites and microbes – including those responsible for filariasis, leprosy (Mycobacterium leprae and M. lepromatosis), schistosomiasis, trachoma (Chlamydia trachomatis conjunctivitis) and soil-transmitted helminths (Zaccone 2006). It may come as a surprise to learn that this is quite a logical proposition, considering our Children in art class, Groote Eylandt, Northern Territory. Children exposed to evolutionary background. Indeed, a natural environment are less likely to develop atopic disorders associated with immune dysfunction, particularly allergic reactions. (Image courtesy Satrina and David Sing and Charles Sing, in a paper examining soil exposure Matt Brandt) (2010), highlight the importance of the environmental influences on the human organism:

Bugs, Bacteria and the Immune System

our immune systems are the result of around 3 million years of natural selection for genetic variations that produce the antibodies that protect life from adverse effects of exposure to environmental agents that have the potential to threaten the integrity of biological processes that support life. The inherited biological abilities of the immune system to isolate the human organism from pathogenic invaders that have their origins in the soil is essential for avoiding disease. The water we drink, the Aboriginal Australian child, Yirrkala, Northern Territory, 30 August 1948, Robert food we eat and the air we breathe, Miller. Part of the collection ‘American-Australian Scientific Expedition to Arnhem regardless of geographic location, can Land, Northern Territory’. (nla.pic-vn4492958-v) include minerogenic, biogenic and

A DESIRE FOR DIRT? anthropogenic components of the soil that can act as antigens.

We simply cannot get away from the stuff. This level of integration between the human organism and the environment is reflected in parasite exposure – and not all effects on the body are detrimental. Indeed, the need for parasite infection may be hardwired into the human host. Exposure appears to go beyond the body merely coping with an episode of infection – encounters with parasites actually ‘shape the genetic predisposition to autoimmune conditions’ (Fumagalli 2009). This is quite an extraordinary concept that links individual human health ever more intimately with environmental experiences. Basically, we evolved with worms in the ecosystem and we have been designed to cope with them (Zaccone 2006; Callahan 2003; Hamilton 1998).

A Diversity of Worms There are two major groups of intestinal worms (helminths) that are of interest to human health. They are the roundworms (nematodes) and flatworms (platyhelminths) – both have an extraordinary long history of association with their human host. Helminths were around at the same time as the dinosaurs. They have been found in ancient mummies, as well as ancient petrified human waste. The fact that most helminths have a restricted selection of hosts attests to a remarkably long evolutionary link, which some have suggested may deserve consideration as symbiotic association – rather than being classed as parasitic. Weinstock and Elliott (2009) comment: ‘This has been achieved through millions of years of coevolution allowing time for both the parasite and its host to gradually adjust to this relationship. Many worms seem invincible to human defense.’ It is imperative for these parasites that they are able to manipulate their environment so that they maintain the viability they need to be able to develop, reproduce and complete their life cycle. Helminth survival adaptations are exceptionally effective, with some even eliciting alterations of the host’s response. Normally,

hostile changes occur that aim to evict or kill the parasite. Therefore, achieving successful colonisation usually involves evading or quelling their host’s defences in some manner. The worm needs to evade destruction by either changing its environment or simply hiding. Strategies that involve switching off the inflammatory immune response of the host thereby induce a tolerant response to the antigens of the parasite: ‘Parasites themselves wield an astonishing array of mechanisms to evade the ravages of the host’s immune system and in so doing ameliorate the more self-destructive aspects of a response [from the host]’ (Zaccone 2006). Many worms even have an adaptable outer skin (integument) that can absorb molecules from the host, which they then use as a cloaking device. Utilising a host as part of a parasite’s life cycle is obviously a very complex business. There is a delicate balance to be maintained because the parasite has to avoid overwhelming the host – as

Ascaris lumbricoides, fertilised egg. (Courtesy Dr Mae Marvin, CDC)

Ascaris lumbricoides, showing that the female is larger than the male. (Courtesy CDC)

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it is not a particularly good long-term survival strategy to irreparably damage its environment. There are two main helminth classifications of interest: • Common human roundworms are the Giant Intestinal Roundworm (Ascaris lumbricoides), Hookworm (Necator americanus), Whipworm (Trichuris trichiura), Pinworm (Enterobius vermicularis) and Threadworm (Strongyloides stercoralis). There are also filarial worms (notably Wuchereria bancrofti and Brugia malayi) that are responsible for lymphatic filariasis (the chronic form is known as elephantiasis). • Human flatworms fall into two classes: flukes (trematodes) and cestodes. The latter includes intestinal tapeworms such as those from beef (Taenia saginata), pork (T. solium) and fish (Diphyllobothrium latum). Flukes include Bilharzia (Schistosoma spp.), liver flukes (Clonorchis spp.), intestinal flukes (Fasciolopsis spp.) and lung fluke (Paragonimus sp.). It is well documented that worm exposure can benefit the immune system. Infected tissue (primarily in the gastrointestinal tract) is stimulated to produce higher levels of T-cell cytokines (including interleukins) that confer a level of protection against atopic conditions. In general, however, the potential for disastrous consequences associated with helminth infection has tended to override these considerations, and thus infections tend to be aggressively controlled by drug treatment. Unfortunately, this has resulted in an avenue of vulnerability for the immune systems of many children (McKay 2008; Callahan 2003). Indeed, worm (anthelmintic) treatments have been shown to increase the frequency of allergic sensitivity to the house dust mite (van den Biggelaar 2004). Clinical studies have confirmed the benefits of ‘helminthic therapy’, notably the use of Trichuris suis (pig whipworm) and human Hookworm (Necator americanus) for Crohn’s disease. Numerous other conditions can benefit from this type of therapy: ulcerative colitis17, inflammatory bowel disease, multiple sclerosis, diabetes (type 1)18, dermatitis, eczema, hay fever, asthma and food allergies. Interestingly, the type of worm infection may be

specifically related to a condition. For example, asthma responded to therapy with Hookworm (Necator americanus), but Roundworm infection (Ascaris lumbricoides) increased the risk of attacks (Weinstock & Elliott 2009; Leonardi-Bee 2006; Croese 2006; Zaccone 2006). Ascaris suum infection has been shown to prevent allergic eye disease due to ragweed pollen in mice (McKay 2008). Childhood infection with Schistosoma haematobium has also been shown to induce a parasite-specific immune response that can suppress atopic reactivity (van den Biggelaar 2001). 17 The benefits for ulcerative colitis were more modest in comparison to the quite high success rate (around 80%) in Crohn’s disease patients (Zaccone 2006). 18 Childhood diabetes is rare in most African and Asian populations – as is multiple sclerosis. European agricultural communities also have a much lower incidence of diabetes (Zaccone 2006). Recent research has demonstrated interesting links between the immune system and helminth infections, which influence the development of metabolic syndrome and diabetes (Wu 2011).

Helminth Therapy

Trichuria suis. (Courtesy Universidad de Córdoba; CC-by-SA 3.0 Unported)

Human Whipworm (Trichuris trichiuria), from Traité zoologique et physiologique sur les vers intestinaux de l’homme John Gottried Bremser, 1824. Published by CLF Panckoucke in Paris (in French).

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Trichuris suis is the whipworm that infects pigs. It is also the species utilised in deliberate helminth infection of humans because the infection is self-limiting and not readily transmissible. Clinical exposure can result in significant improvements in individuals suffering Crohn’s disease – its use being linked to an extremely high remission rate (70–75%). The parasitic worm triggers immune system reactions, including mucous secretions in the gut that provide lasting benefits (Jabr 2010; McKay 2008; Summers 2005). Other parasites that have been linked to benefits for intestinal function include Schistosoma mansoni (a blood fluke), Trichinella spiralis (‘pork worm’) and Hymenolepis diminuta (rat tapeworm) in experimental colitis – as well as Heligmosomoides polygyrus (a rodent nematode) for inflammatory bowel disease, as well as arthritis, asthma and allergic airway inflammation (McKay 2008; Dunne & Cooke 2005). A number of parasites have also shown experimental benefits for allergeninduced airway inflammation in animal studies – Nippostrongylus brasiliensis (a rodent gastrointestinal nematode), Litomosoides sigmodontis (a parasite of bats) and Schistosoma mansoni (male cercariae only) (McKay 2008).

Necator americanus larvae (10–35 larvae) are applied to the skin during treatment for Crohn’s disease – which can involve a single session or multiple smaller amounts over 2–3 months. (Image courtesy Jasper Lawrence, CC-by-SA 3.0 Unported)

Heligmosomoides polygyrus, sourced from the digestive tract of a rodent (Apodemus sylvaticus), shown under an optical microscope. (Image courtesy D Davesne, Wikimedia Commons, CC-by-SA 3.0 Unported)

The development of multiple sclerosis (MS) is another condition that appears to have a link with human Whipworm infection. MS patients who developed trichuriasis experienced fewer exacerbations, and developed fewer brain lesions, when compared to patients who remained uninfected (Correale 2007; Fleming & Fabry 2007; Fleming & Cook 2006). Experimentally, there are other parasites or bacteria that have been linked to an amelioration of allergic encephalomyelitis, which is indicative of potential benefits for multiple sclerosis – Schistosoma mansoni, Mycobacterium bovis (the organism responsible for bovine tuberculosis) and Bordetella pertussis (the cause of whooping cough). In addition, studies of collagen-induced

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arthritis have suggested benefits from exposure to Acanthocheilonema vitae (a rodent filarial worm), Trypanosoma brucei (the ‘sleeping sickness’ parasite) and Streptococcus sanguinis (a bacterium associated with dental plaque development and bacterial endocarditis) (Dunne & Cook 2005).

The Bilharzia Parasite

Schistosoma mansoni (cercariae: free-living freshwater larvae), indirect fluorescent antibody stain. (Courtesy Dr Sulzer, CDC)

Schistosoma parasite eggs in bladder tissue. (Courtesy Dr Edwin P Ewing Jr, Centers for Disease Control and Prevention (CDC) Schistosoma mansoni worms: a pair of worms (left); smaller female (middle), male worm (right). (Courtesy CDC).

Schistosoma mansoni (trematodes). Marianna Wilson, CDC)

(Courtesy

Disease-producing parasites with useful sideeffects can come from unexpected sources. Schistosomiasis is a chronic disorder with quite profound repercussions. There are three

main types, which are associated with five different parasites: intestinal schistosomiasis (Schistosoma mansoni and S. intercalatum), urinary tract schistosomiasis (S. haematobium) – and Asian schistosomiasis (S. japonicum and S. mekongi). The disease is characterised by skin problems (itching, eczema), fever, fatigue, cough, abdominal pain, diarrhoea and genital sores. A high white cell count (eosinophilia) is common as the body reacts to the infection. Serious complications can affect the nervous system, urinary tract, liver and spleen – as well as result in the development of anaemia or hypertension, depending on the parasite species involved.

A DESIRE FOR DIRT?

However, Schistosoma parasites are masters of avoiding destruction by the human immune system. Indeed, schistosomes can live in the bloodstream for up to 40 years. To do so they deploy some impressive strategies designed to evade the immune system (cloaking themselves using host antigens; enzymatic cleaving of antibodies), or run a rapid repair system (the use of a pre-formed membrane, and a doublemembrane system, to fix tissue damage). The parasite can also use the host’s own immune system to support its development and transmission. In doing so it has a rather remarkable potential to alter the immune response in beneficial ways (see Dunne & Cook 2005 for technical details). Certainly, exposed human populations do not have a high incidence of allergic disorders (Zaccone 2006). Experimentally, a number of studies of Schistosoma mansoni infection have shown beneficial activity for diabetes (type 1), multiple sclerosis, Grave’s thyroiditis, allergic airway inflammation, colitis and arthritis (McKay 2008; Dunne & Cooke 2005). In addition, individuals suffering schistosomiasis were found to avoid the arterial fibrous plaque accumulations that are associated with an increased risk of heart attack. Preliminary experiments with Schistosoma infection in mice prone to arteriosclerosis showed that the incidence of arterial constriction was halved and cholesterol levels were lowered significantly. The use of Schistosoma in a practical clinical sense would be impossible, therefore research has been initiated into locating the chemical the parasite excretes that may be responsible for these effects (Randerson 2002).

A Parasite that Influences Behaviour?

There is much more to the world of parasites than we are truly aware of – despite our growing appreciation of their role in human immune system development and function. The toxoplasmosis parasite (Toxoplasma gondii) is a particularly intriguing example that

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Toxoplasma gondii constructing daughter parasite cells within the mother cell. (Courtesy Ke Hu and John Murray)

not only manages to strategically evade the host’s immune system. Studies have suggested that it can cause profound changes in mental function – demonstrating an entirely new way in which parasites may influence their host. Toxoplasma spends part of its life cycle in rats and then must transfer to a cat to reproduce. This would appear to be a strange arrangement. However, as cats naturally eat mice, it is probably not as inconvenient for the parasite as it would first appear. To increase the odds of transferral, Toxoplasma actually causes damage to the part of the brain (the amygdala) that makes a rat instinctively fear cats – which pretty well ensures the rat will land up as dinner (Vyas 2007; Berdoy 2000). Due to the close relationship between cats and the community, human infection is not uncommon. It is usually associated with a mild flu-like condition and, until recently, the parasite was thought to then lie dormant. Research has surfaced that now suggests a more profound influence when the parasite infects brain tissue. Toxoplasma seems associated with conditions such as chronic inflammatory headache, visual disturbances, migraine and epilepsy. The fact that the parasite can compromise neurological and immune system functions also suggests a link with related disorders such as chronic nervous system dysfunction (neuropathy, chorea), meningitis and brain tumours – as well as problems such as celiac disease, Crohn’s disease and Henoch–Schönlein

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purpura19 (Prandota 2009, 2007). In immunecompromised individuals this type of infection can be catastrophic, resulting in encephalitis (PereiraChicolla 2009). The extent to which Toxoplasma influences human behaviour and mental function may be frighteningly significant. Recurrent ruptures of Toxoplasma cysts in the nervous system and brain can lead to a chronic inflammatory state – albeit the effect may be virtually undetected.20 The parasite has the potential to alter mood and cause personality changes, as well as having an association with learning difficulties (including ADHD). Personality disorders (e.g. delusions, hallucinations, paranoia) with alterations in brain chemistry may even be induced by the parasite, or inflammatory changes that occur when the cysts in the brain rupture (Fekadu 2010; Prandota 2009; Lafferty 2006). Individuals with latent toxoplasmosis appear more likely to be involved in traffic accidents due to a decreased ability to concentrate or focus their attention (Sergiev 2010; Henriquez 2009). It was an early study of psychiatric hospital patients in Mexico that suggested the link with disturbances in brain function.21 In-patients were found to have a higher infection rate (18%) than the general population (9%, based on blood donor figures). However, those suffering schizophrenia had a much higher infection rate (26%). There also appeared to be a positive link with sexual promiscuity (Alvarado-Esquivel 2006). Overall, toxoplasmosis is thought to be present in around a third of the world’s population – which implies that nearly 2 billion people could be chronically affected (Henriquez 2009; Prandota 2009). In some regions, the infection can occur in a sizeable proportion of the population: France (pregnant women in Paris: 51–71%; Jeannel 1988); and parts of Sweden (55%; Birgisdottir 2006) – with the latter showing possible links with an increased incidence of asthma. An Israeli study found greater infection levels in Arab villages 19 This is a skin disease characterised by purpura – small rash-like dots of blood haemorrhage in the skin. Joint and abdominal pain are common associated symptoms. In some cases there may be kidney involvement, which can lead to chronic dysfunction. 20 Numerous drugs can induce side-effects in the brain – some of which may even be linked to an inflammatory or immune reaction that could ‘reactivate cerebral toxoplasmosis’. See Prandota 2009 for a comprehensive list of disorders that are potentially associated with toxoplasmosis infection. 21 Experimentally, the anti-psychotic drug haloperidol can inhibit the growth of T. gondii (tachyzoites) in vitro. This is also suggestive of a chemical link between the parasite and behavioural problems (Henriquez 2009).

Silkworm cocoons. A silk protein extract from Silkworm cocoons (Bombyx mori) has shown significant immunosupportive properties. Studies have demonstrated that this protein bolstered the immune system of mice, providing protection against acute Toxoplasma gondii infection (Moon 2011). In addition, recent studies suggest Silkworm extract could have anticancer potential (Yue 2009). Silkworms have long been utilised in Chinese medicine as an anti-inflammatory, analgesic and anticonvulsive remedy (see Volume 1 for details). (Image courtesy Krish Dulal, Wikimedia Commons, CC-by-SA 3.0 Unported)

(58%), than in kibbutzim (22%), with infection rates being significantly higher in older members of the community (Raz 1993). The incidence was even higher in Iran (78–80%; Sharif 2007) – while moderate rates were found in England (28%; Joynson 1992) and the United States (17–29% in different parts of the country). The occurrence of the disorder in Iceland and Korea was substantially lower (10% and 6%, respectively; Birgisdottir 2006; Lee 2000).

A Serious Threat to Australian Wildlife While few native mammals and birds appear to suffer overt symptoms from toxoplasmosis, marsupials are much more sensitive – which has worrying implications for some Australian wildlife. Cases have been reported in a range of native animals:

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However, because feral cats are prevalent throughout Australia, this is unlikely to reflect the true extent of the problem. The Toxoplasmosis Fact Sheet of the Australian Wildlife Network comments: ‘While toxoplasmosis has the potential to cause significant mortality of wild marsupials its impact on wild populations is unknown. It has been cited as a cause of decline of the endangered Victorian brush-tailed rock wallaby but no evidence has been found to support this theory. Successful treatment of the condition remains elusive and as long as feral cats are spread throughout the country prevention will not be possible’ (www.wildlifehealth.org.au). ‘Old man’ Eastern Grey Kangaroo (Macropus giganteus).

Tawny Frogmouth (Podargus strigoides).

• Tasmania: Tasmanian Pademelon (Thylogale billardierii), Common Wombat (Vombatus ursinus) and Bennett’s Wallaby (Macropus rufogriseus); • Western Australia: Western Grey Kangaroo (Macropus fuliginosus) and Southern Brown Bandicoot (Isoodon obesulus); • New South Wales: Tawny Frogmouth (Podargus strigoides); • Queensland: Agile Wallaby (Macropus agilis) – as well as a Dugong (Dugong dugon); • Victoria: Common Wombat.

Medicinal Mycobacteria

Similar to the links with parasite infections, discoveries regarding the importance of soil microorganisms have found an interesting association between mycobacteria and the human immune system – which would have evolved over 10,000–20,000 years of mutual association. This highlights the potential of diverse aspects of the environment to have a profound influence on immune system development and general wellbeing – an aspect of our existence on this planet that has been greatly under-estimated. While most mycobacteria do not cause disease (are non-pathogenic), tuberculosis and leprosy are well-known exceptions. Similar to helminth exposure, mycobacteria appear to be an essential part of the environmental ‘education’ of the immune system. Lack of exposure can compromise the function of T-cells, causing an imbalance that is implicated in allergic reactions – as well as a higher incidence of asthma, arthritis and, possibly, a range of the debilitating immune disorders that seem to increasingly plague humanity (Callahan 2003; Hamilton 1998). Experiments have suggested that contact with Mycobacterium bovis and M. avium are linked to a reduction in the incidence of diabetes (type 1), and with M. bovis to multiple sclerosis (Dunne & Cook 2005). This theory originated with the finding that mycobacterial exposure dramatically stopped allergic responses in experimental mice. Later, a practical demonstration of the usefulness of mycobacteria was discovered in children given BCG anti-tuberculosis

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vaccinations in Myanmar (Burma) and the southern United States.22 The mycobacteria altered responses to the vaccine. The suggestion that deliberate exposure to these bacteria would help to re-educate the immune system is therefore not unexpected (Hamilton 1998). Certainly it seems that childhood forages into the world of earth may well have immeasurable benefits for their future health. Recent clinical studies have shown that a nonpathogenic mycobacterial species (Mycobacterium vaccae23) had good potential for the treatment of tuberculosis. This deserves serious consideration for practical development, as the disease has become resistant to many standard anti-tuberculosis drugs (Yang 2010). This form of therapy may well have significant potential benefits for immune system problems including asthma (Yazi 2008) – but not, unfortunately, atopic dermatitis or psoriasis. Exposure has also shown an influence on brain function, as Mycobacterium vaccae has a clinical antidepressant effect by inducing the brain to produce serotonin (Miller 2010; Lowry 2007; O’Brien 2004). Animal studies have suggested a reduction in anxiety behaviour and enhanced learning ability (Jenks & Matthews 2010; Matthews & Jenks 2010). Initial studies of Mycobacterium indicus pranii (another non-pathogenic mycobacterium) have shown clinical benefits for bladder and lung cancer. This appears to be associated with immunosupportive effects (Ahmad 2011). The links between humans and the environment are certainly much more intimate than many have hitherto suspected. Perhaps, then, one should not be surprised by the fact that some forms of clay had a reputation as a remedy for respiratory disorders. Wittich (1589) noted with regard to Terra Sigillata: ‘“this earth of ours” cures quinsy, inner inflammations, ulcered lungs, and other inward diseases if a drachm is taken in a liquid proper to the disease. It could also be used for colic and “iliac passions”.24 This earth helps in all

diseases where sweating was important to the cure and in consumption with the spitting of blood’ (cited in Dannenfeldt 1984).

22 The bovine tuberculosis bacillus (Mycobacterium bovis) is the basis of the BCG vaccine for tuberculosis prevention, which has given very good results (80% protection), although some variability can occur depending on the strain used for vaccine preparation.

Therapeutic Earthworms

.

23 M. vaccae was originally isolated from cow dung in Austria. It is one of the soil bacteria that can detoxify ground soil pollutants (Burback & Perry 1993). 24 A particularly nasty form of intestinal obstruction leading to vomiting of faecal matter

BCG vaccine, saline and needles for use as a multipuncture injection in Japan. The use of the BCG vaccine (sourced from attenuated Mycobacterium bovis) is known to offer some protection (26%) against leprosy – and has been suggested for treating Buruli ulcer (M. ulcerans). In addition, BCG has been used as an immunotherapy for bladder cancer and colorectal cancers – benefits that appear to be linked to a stimulation of immune system function. Its use has also been suggested for diabetes (type 1), cystitis (bladder inflammation) and multiple sclerosis, while some preliminary research has proposed a neuroprotective effect for Parkinson’s disease. (Image courtesy Y Tambe, Wikimedia Commons, CC-by-SA 2.5, 2.0, 1.0)

There is another wormy creature of medicinal import – the value of which has been largely ignored by modern science, at least until recently. In 1881 Charles Darwin wrote the first major evaluation of earthworm ecology in his essay on The Formation of

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Dried Earthworm, Di Long, for use in Chinese medicine. The Chinese name for the earthworm translates to the rather wonderful term ‘earth dragon’ which, in a way, shows how respected this small animal is for medicinal purposes. Pharmaceutically it is known as Lumbricus.

Vegetable Mould through the Action of Worms, with Observations on their Habits. He noted the vital role of the earthworm in producing soil and concluded: ‘It may be doubted whether there are many other animals which have played so important a part in the history of the world than the earthworm’. More than a hundred years earlier, a letter by Gilbert White to Daines Barrington – found reproduced in White’s Natural History of Selborne (1789) – revealed similar opinions on the subject. No doubt other naturalists had wondered about the importance of this ubiquitous worm, albeit none had formally accorded them the recognition they deserved. Earthworms were regarded as little more than an unattractive, unsightly wriggling pest. Earthworms have been a rather unusual source of folk remedies. In general, the therapeutic use of worms was considered to be merely an unsavoury practice indulged in by an odd fringe of society. Even so, long ago some European traditions recognised the earthworm’s value as a medicine. Dioscorides recommended mashed earthworms to glue together

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‘sinews cut asunder’ and for treating malaria. In combination with goose-grease, the humble worm provided a remedy for ear problems, toothache, and had value as a diuretic. Pliny also thought earthworms cooked in oil were useful for toothache – as were earthworm ashes. Earthworms were included in the first London Pharmacopoeia (1672), where two spoonfuls in a little water were taken on a fasting stomach to treat apoplexy, convulsions, dropsy, jaundice and, indeed, gastrointestinal worms. The effects were noted to be diuretic, sudorific, cephalic, antilithic (removing stones), anthelmintic (removing worms) and galactagogue (promoting the flow of breast milk). Boiled in oil to make an ointment, worm remedies were applied as an analgesic to inflamed gouty joints and to heal fractures. They were believed to strengthen the nerves and joints, and were used as to make a healing salve for whitlows (a very painful infection of the fingertip). Distilled in wine (arguably the best way to take them) they provided a cure for the bites of venomous animals such as snakes, centipedes and dogs (Read 1943). Despite the fact that some folk tales have hinted at a poisonous potential, investigations of Di Long have not demonstrated toxic effects. Old European medicine accorded earthworms an excellent reputation for the treatment of lung complaints – and there would appear to be some truth in this tale. The remedy has shown anti-histamine and bronchodilatory properties that will help to stop wheezing, making it useful for breathing problems associated with feverish conditions and asthma (Chu 2007). In Chinese medicine, Earthworm has been combined with other herbs to enhance its effectiveness. Clinical studies demonstrated its usefulness with Chinese Skullcap (Scute, Scutellaria baicalensis) as an intramuscular injection for treating uncomplicated asthma (40% success). Old records mention a Chinese recipe that utilised nine old and thirty-four new Earthworms for treating pneumonia with difficult respiration. It was also considered useful for oedema, pain of the hands and feet, loose and bleeding teeth, carbuncles and even leprosy. The remedy has substantial diuretic effects, which made it useful for cases characterised by fluid retention, as well as for easing burning painful dysuria and anuria (lack of urination) in the aged (Bensky & Gamble 1986; Yeung 1985).

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In Chinese traditions the Earthworm is a respected remedy that continues to be employed to this day. Powdered, liquefied or made into an ash (depending on the prescription), the remedy is sourced from two species of worm: Pheretima aspergillum (family Megascolecidae) and Allolobophora caliginosa trapezoides (family Lumbricidae). Clinically, worm remedies are considered useful for feverish disorders (malaria, typhoid, childhood fevers). They possess anticonvulsant and analgesic properties useful for treating seizures, rheumatic pain and the after-effects of stroke (hemiplegia). Earthworm has been a specific for disorders classified as ‘true heat’ conditions, and its use is contraindicated when these characteristics are not present. Experimentally, Di Long has demonstrated sedative and hypotensive properties. It has been used clinically for the treatment of essential hypertension – with a good rate of success (90%). Its vasodilatory activity was attributed to an effect on the central nervous system (Bensky & Gamble 1986; Yeung 1985). Its traditional use is supported by studies showing the Earthworm has diuretic, antispasmodic, antimicrobial and anti-inflammatory properties (Cooper & Balamurugan 2010). In India, Earthworms have been equally valued as an antiulcer, antioxidant and anti-inflammatory remedy. Investigations of an ‘earthworm paste’ made from Lampito mauritii demonstrated activity comparable to the anti-ulcer drug ranitidine in animal studies (Prakash & Ranganathan 2007). Other investigations of anti-inflammatory, febrifugal, liver-protective (hepatoprotective) and liver-restorative properties of earthworm paste (sourced from Lampito mauritii and Perionyx excavatus) are equally significant. Earthworms are rich in phenolic compounds, which doubtless contribute to their pharmacological properties (Cooper & Balamurugan 2010; Balamurugan 2008, 2009, 2007; Prakash 2008; Ismail 1992). The earthworm Lumbricus rubellus contains a rather interesting proteolytic enzyme complex named lumbrokinase. Even in the 1880s Charles Darwin had observed the Earthworm’s remarkable digestive capacity, which he compared to the pancreatic secretions in humans: ‘The digestive fluid of worms is of the same nature as the pancreatic secretion of the higher animals; and this conclusion agrees perfectly with the kinds of food which worms consume. Pancreatic juice emulsifies fat, and we have just seen

Common garden earthworm (Lumbricus sp.). (Courtesy Michael Linnenbach CC-by-SA 3.0 Unported)

how greedily worms devour fat; it dissolves fibrin, and worms eat raw meat; it converts starch into grapesugar with wonderful rapidity, and we shall presently show that the digestive fluid of worms acts on starch.’ Lumbrokinase has experimental anti-thrombotic properties and has been investigated clinically for the treatment of angina pectoris (Kasim 2009; Ge 2005; Zhao 2005; Kim 1998; Hahn 1997; Mihara 1991). This means that lumbrokinase can decrease fibrinogen in the blood, thereby reducing blood viscosity and platelet aggregation – which reduces the tendency of the blood to clot. The body’s coagulation system is very finely tuned and, interestingly, lumbrokinase does not appear to upset the balance, rather it acts to restore normal coagulation parameters (Cooper & Balamurugan 2010). Its use did not have the sideeffects (notably bleeding) that have been associated other drugs such as streptokinase and urokinase (Cooper 2004b). There are also suggestions that some fibrinolytic (fibrin-dissolving and clot-preventative) molecules have useful antimicrobial potential. This is of interest because an antimicrobial peptide, lumbricin I, from Earthworm extracts has demonstrated a broad spectrum of activity against fungi, gram-positive and gram-negative bacteria (Cho 1998). Certainly, the research tends to support many of the traditional recommendations for the use of Di Long in conditions such as stroke, limb numbness

A DESIRE FOR DIRT?

and hemiplegia. It appears that Earthworm enzymes may have medicinal qualities that could be utilised in the treatment of a greater range of ischaemic problems (loss of blood supply) including cardiovascular, cerebrovascular and eye disorders, pulmonary infarction and hearing loss – as well as some forms of cancer. Extracts of the earthworm Eisenia fetida have shown anti-tumour activity in various cancer cell lines and animal studies. Earthworm components (particularly lombricine and eisenin I) have experimental cancer inhibitory and retardant activities. There are numerous other conditions associated with blood clotting (hypercoaguability) that tend to suggest the therapeutic value of this remedy could be substantially more extensive (Cooper & Balamurugan 2010; Yan 2010; Cheng 2008; Ji 2008; Sun 2006; Zhao 2005; Cooper 2004a, 2004b; Hrzenjak 1998; Ryu 1994). Even so, a lot of work remains to be done to determine the true value of the humble Earthworm.

beneficial compounds to detoxify the soil. With over 3000 species of earthworm, some have unique adaptive skills – such as the large blue earthworms of the northern Queensland tropics, or the Giant Gippsland Earthworm that grows up to 4 metres long (New Scientist 2002, Taylor 2002).

Egg cocoons of the Common Earthworm (Lumbricus terrestris). (Courtesy Clive A Edwards, Ohio State University, Columbus)

Earthworms for the Environment Despite the fact that there have been numerous advances in understanding this small, crawling denizen of the earth, even today many do not truly appreciate the role the Earthworm has played in producing and maintaining the planet’s basic organic structure. Soils are hard to develop – for every couple of centimetres of soil, 1,000 years of climatic weathering and organic decomposition have passed. Earthworms make a huge difference to soil quality, opening avenues for the access and distribution of nutrients and oxygen. Truly, the work of a worm is never done. Ecotoxicology is a new aspect of earthworm biology which studies them as indicators of soil quality and, consequently, for the detection of toxic residues. Pesticides and herbicides affect earthworms directly, quickly influencing their ability to reproduce and survive. The number and viability of egg cocoons is a sensitive measure of the quality of life underground. Even the membrane of the worm blood cell can be used as a sensitive indicator of chemical stress. Earthworm burrowing habits can promote the clean-up of contaminated land sites, by allowing

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Burrow of a common earthworm, showing the substantial depth that these creatures penetrate the soil. (Courtesy United States Department of Agriculture, North Appalachian Experimental Watershed, USDA-Agricultural Research Service, Coshocton, Ohio)

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 The link between earth, microorganisms, helminths and human health is obviously profound. We have learned to deal with a remarkable array of microorganisms that permeate our environment. Indeed, our bodies even ensure that their presence is used to our advantage: ‘The surfaces of the healthy human body, both external (skin) and internal (sinuses and lungs, the alimentary canal), are populated with a plethora of species of microorganisms. The total numbers of microbial cells that reside in or on a healthy human … outnumber the body’s own cell count by at least an order of magnitude. Some of these microorganisms assist the immune system in protecting the body from pathogenic microorganisms. Many are essential inhabitants of the gut necessary for extracting nutrients from food’ (Sing & Sing 2010). Truly, this gives a new meaning to the idea that ‘we are never alone’. Unfortunately, contamination of the biosphere is a prevalent, and unavoidable, problem of modern existence: ‘Contemporary genetic studies of how the immune system responds to particular components of airborne dust are compromised by the levels of anthropogenic [human-derived] pollutants which permeate the atmosphere at all levels and at all geographic latitudes. Quite simply, there is nowhere on earth to study the genetic basis of the response of the immune system to airborne dust where the air does not contain a mix of human-produced hydrocarbons, radioactive isotopes and other anthropogenic materials that did not exist throughout most of evolutionary history of our species’ (Sing & Sing 2010). No wonder there is an increase in the incidence of disorders characterised by inflammation, allergy and respiratory distress. We have irrevocably changed the planet, for better or worse, it appears. A very sobering thought indeed.

Dead carp – victims of pollution. Humans have been using pollutants for a long time and incidents of poisoning are an all too familiar result of inappropriate industrial effluent release. Marine life is particularly susceptible to disruption of their environment. Mercury provides an example of an air pollutant that has been progressively deposited in soils, which is then leached into surface water – and can ultimately result in significant contamination of fish stocks. The use of persistent organic pollutants (POPs) such as chlordane, toxaphene and PCBs (polychlorinated biphenyls) has caused contamination problems across the globe. These synthetic chemicals have been transported across the world in a vaporised form to later condense and precipitate in locations quite remote from where they originated. In the long term, biomagnification down the food chain results in unacceptable levels in our food supply with highly hazardous repercussions (Abrahams 2002). Even if a total ban on the use of these pollutants was enacted immediately, the contamination process is likely to continue for another century – at the very least. (Image courtesy CDC)

Chapter 7

ARID LANDSCAPES: MEDICINALS AND AROMATICS FROM THE DESERT

An eagle’s eye view of the arid landscape, western New South Wales. The outback can be an inhospitable place. The animals and plants that survive in this environment have made special adaptations to its needs, and it would not be unexpected to find that at least some of the vegetation has pharmaceutical potential. (Image courtesy Peter Woodard)

The arid regions of the Australia not only play host to incredible ancient artworks and mine sites, there is a surprising diversity of vegetation – much of which has been utilised as bush tucker, including numerous forms of ‘bush tomato’ (Solanum spp.) and various ‘native yams’ (genera Ipomoea and Dioscorea).1 The region covers a vast area, where unique floral and faunal adaptations have evolved over the millennia. The Myoporaceae is one of the plant families of the region that gained a level of early repute among collectors and botanists – notably the genera Myoporum and Eremophila, which contain numerous interesting desert species, many of which are endemic.2 A few also have an impressive botanical history that is intimately linked with the early exploration of the continent.

Silky Eremophila (Eremophila nivea), above, is an extremely pretty species from Western Australia with a restricted distribution around Geraldton. Eremophila subteretifolia (below) is a rare species from Western Australia. (Images courtesy Melburnian)

1 The pharmacological properties of these plants are discussed in Chapters 11 and 12 of the current work. See Volume 3 for further details of their use as bush tucker. 2 The Myoporaceae family has recently been reclassified as the tribe Myoporeae and is now considered to be a subsection of the Scrophulariaceae family. To try to minimise confusion the use of the term Myoporaceae is retained in most places in this work becuase it is the original classification that is referred to in all the literature being reviewed and is often present in quotes. For a comprehensive discussion of these

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The Coccid Emu-bush (Eremophila gibbifolia), which was described in 1855 by Baron Ferdinand von Mueller, displays highly unusual wart-like foliage. This species, which is widespread in Victoria, ranges to South Australia – albeit more rarely sighted in this state. Many Eremophila species are known as emu-bushes as the fruit they produce is a favoured food for this native bird. (Image courtesy Melburnian)

William Dampier collected Myoporum insulare from Western Australia in the late 1600s and, almost a century later, Eremophila debilis (under the name Myoporum debile) was an early European import for the nursery trade. Eremophila mitchellii has equally impressive links with Australia’s early explorers. Joseph Maiden (1921b) noted: ‘Eremophila, from two Greek words – eremos, a desert, and philos(a), fond of; Mitchelli [sic], in honour of Colonel Sir Thomas Livingstone Mitchell, who was Surveyor-General of New South Wales from 1827 to his death in 1855. He collected this plant on his expedition to Western Queensland in 1846.’ Mitchell’s diary entry of its discovery reads: ‘We here observed, for the first time, a fine new Eremophila, with white flowers, forming a tree 15 feet high’. The Reverend Tenison-Woods later elaborated: This tree has been found throughout the whole extent of Australia. I have seen it on the edge of the salt-lake region north of Adelaide, and all explorers and collectors have recorded it from central Australia. Forrest in his last exploration traced it to the desert regions of North-west Australia not far from Nichol Bay. Thus we see it is a desert tree found all through the arid regions of tropical and sub-tropical Australia. It well deserves its name (lover of the desert) as it is found in other regions. In many places it goes by the name of Dogwood. It has small dark grey-green linear leaves, and has a bushy appearance by no means inelegant (Tenison-Woods 1882).

Explorer Ludwig Leichhardt’s’ journal described Eremophila debilis (top) as ‘a prostrate Myoporum’, and Eremophila maculata as ‘a small shrubby Stenochilus with very green linear lanceolate leaves and red tubulous flowers’. These species, plus Eremophila bignoniiflora (top), E. latrobei, E. longifolia and E. mitchellii are the only members of the genus that have a tropical distribution. (Upper image courtesy Ruth Palsson, Flickr; above image courtesy Melburnian)

Eremophila oldfieldii is a bird-attracting flower with a lower lip that curls downward with protruding stamens. (Courtesy Melburnian)


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Common Boobialla, Native Juniper or Blueberry Tree (Myoporum insulare) was first described over two centuries ago by Robert Brown in 1810 – as was the Creeping Boobialla (M. parvifolium). Common Boobialla is one of the most widespread of the genus, ranging around the coast of the Australian continent, from northern New South Wales south to Victoria, Tasmania, South Australia and Western Australia. (Image courtesy Melburnian)

Eremophila flowers are designed to attract either birds or insects. White or bluish purple flowers, such as those of Eremophila hygrophana (top), are attractive to insects, and tend to have a protruding lower lip which acts as a landing platform. Bird-attracting flowers are more brightly coloured (orange, reds, yellows or occasionally green), with a lower downward-pointing lobe that allows the bird access while discouraging insects. The flower stamens are also longer to deposit pollen on the bird while it is feeding. (Upper image courtesy Melburnian; lower image courtesy Raffi Kojian, Gardenology.org)

Boobialla Bush Tucker In more recent times the Australian Myoporaceae have become increasingly popular for horticultural and revegetation purposes. Not only do they produce extremely attractive flowers that sustain

Myoporum parvifolium is widespread throughout Victoria, and along the South Australian coast. It is also found in New South Wales. (Image courtesy Stickpen, Wikimedia Commons)

wildlife in difficult arid environments, they are both are drought and salt tolerant – attributes that recommend them for challenging revegetation sites. While a number of species are of interest for their edible ‘bush tucker’ fruits, their flavour appeal can vary considerably. Indeed, those of the Southern Boobialla (Myoporum insulare), while edible, can be a bit of a disappointment: ‘the fruits fail to meet expectations and … are bitterly aromatic and salty-

6a;

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sweet in taste’ (Low 1992b). The salty-sweet fruits of another species known as the Western Boobialla (M. acuminatum, syn. M. montanum) are more palatable – but only when ripe. Those of the Amulla or Winter Apple (Myoporum debile) have a similar reputation (Low 1992; Maiden 1900). Overall, Tim Low (1992a) concludes: ‘as a food of birds, they are perhaps best left to the birds’. Aboriginal people tend to agree (Wightman 1994). While in general the native members of the genus have been of little medicinal importance, Myoporum debile was mentioned as a treatment for venereal disease (Webb 1948) – while an infusion of the Waterbush (M. montanum) was used as a wash for the head to treat general disorders in the Northern Territory (Isaacs 1994). Myoporum acuminatum leaves were also utilised in Central Australia for preparing a medicinal wash, and the smoking branches used as a fumigation remedy for general ailments. The latter two species produce a white gum that oozes from stems, which has been used as glue (Latz 1996; Low 1992a). The Native Myrtle or Waterbush (Myoporum acuminatum) is known to be a stock toxin, although because its leaves are distasteful it is rarely eaten. Myoporum deserti (now Eremophila deserti) has a similar reputation, which earned it the common name Ellangowan Poison Bush. The leaves, which are highly toxic, have a burning and bitter taste – although Mitchell commented that the tree ‘put forth sweet and edible fruit’ (see page 311 and Table 7.2). Records of the medicinal use of Myoporum in other places (the genus extends into the Pacific) appear to be equally sparse. There is, however, an interesting refence to the use of Sandalwood and the Hawaiian Naio (Myoporum sandwicense) as a remedy for ‘nose growths’, which suggests anticancer potential.3 These herbs were infused with Cordyline terminalis to make a liquid in which a pad of tree fern hairs was soaked – this was then held to the nose frequently during the day (5–6 times). Another remedy utilised Naio powder mixed with powdered bamboo to ease stomach-ache. Furthermore, a decoction prepared from a ‘hatful’ of leaves, with the fruit and flowers of 10 plants, was utilised for asthma and allied respiratory problems, as well as gynaecological disorders (womb or vaginal 3 Although an analysis of Myoporum wood oil does not appear to be available, that of Eremophila mitchellii, also known as ‘Bastard Sandalwood’, has shown cytotoxic activity (see page 300).

Top, the Weeping or Slender Myoporum (Myoporum floribundum) and above, M. petiolatum – the latter was formerly listed under M. viscosum, which is now considered to be a rare species. (Images courtesy Melburnian)

The Hawaiian herb Naio or Naieo (Myoporum sandwicense) has been utilised as a substitute for Sandalwood when the local supplies were exhausted – albeit regarded of inferior quality, hence Naio’s reputation as a ‘Bastard Sandalwood’. In the Cook Islands the wood was valued for scenting coconut oils used for massage and, in ancient times, played a part in the mummification process (Riley 1994; Whistler 1992). It would probably have been utilised in a similar manner in Hawaii as a massage oil, as this is a popular element of Island culture in the Pacific. In addition, a traditional Hawaiian anti-dandruff and anti-louse hair wash was prepared from a ‘hatful’ of Sandalwood leaves, crushed and steeped in water with a couple of bark pieces, and Naio ash added (Riley 1994). (Images courtesy Kim & Forest Starr, Hawaii)


complications) (Riley 1994). Little appears to be known with regard to the biochemical potential of this species or the validity of these claims.

The New Zealand Ngaio

Myoporum laetum. (Courtesy Julio Reis, Wikimedia Commons, CC-by-SA3.0 Unported)

Ngaio flower (Images Wikimedia Commons)

courtesy

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The Ngaio of New Zealand (Myoporum laetum) and a few Oceanic Myoporum have had more extensive medicinal uses than the Australian representatives of the genus. Ngaio held a good reputation as an insect repellent for irritating pests such as mosquitoes and sand flies – a characteristic shared with the Hawaiian Myoporum sandwicense, which has a very similar common name, Naio. In New Zealand, Myoporum laetum has had some interesting medicinal uses. The inner bark infusion (outer bark removed) was popularly applied to heal ulcers, old sores, itching skin problems and eruptions. The leaf infusion

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had a comparable reputation, as well as being employed as a preventative for warts, to heal chilblains, and to treat eczema. The leaves (bruised and warmed to release the fragrant oil) were said to have a good effect on septic wounds, with an excellent drawing action for poisoned injuries. Ngaio bark, in combination with Karaka (Corynocarpus laevigatus) leaves or other additives such as brandy, has been utilised for pain relief – although these concoctions were reputed to taste quite vile. It was often combined with Matai (Prumnopitys taxifolia) as an astringent for treating all manner of traumatic injuries (including fractures, dislocations, sprains, bruising). In addition, the twigs and leaves were added to vapour baths for those suffering painful disorders such as rheumatism. Ngaio was even said to be an effective leprosy treatment – the inner bark juice taken or the plant used as a wash – although the remedy was rarely taken internally. The juice of the inner bark had a good reputation for easing toothache – as did the New Caledonian species, Myoporum tenuifolium. The dark sticky leaf buds have also been utilised for diarrhoea or dysentery, as well as being chewed as an antidote for mussel poisoning (Riley 1994; Brooker 1993). The latter use is interesting, as the related species Myoporum bontioides has been used in Taiwan as a poison antidote4 (Perry & Metzger 1981). 4 Epingaione from this species has shown good broad-spectrum antifungal activity, with potential for use as a fungicidal agent (Yecheng 2008).

Native Australian Myoporaceae: A Complex Classification The native Australian Myoporaceae (now in the family Scrophulariaceae) were described and classified early in the botanical history of the colony – Myoporum by Georg Forster in 1786, and Eremophila by Robert Brown in 1810. The genus Eremophila is the largest of the classification, with around 240–250 species

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Myoporum tenuifolium. Although the genus name Myoporum was first published by Georg Forster, he attributed the origin of the name to Daniel Solander – who had collected a species on James Cook’s first voyage. Forster collected samples of Myoporum laetum and M. pubescens from New Zealand, as well as M. crassifolium and M. tenuifolium from New Caledonia. (Image courtesy mantisxxl, flickr)

– although at different times they have been variously classified as Bontia, Disoon, Pholidia or Stenochilus. These shrubs or small trees usually inhabit the more arid regions of the continent, predominating in Western Australia. Today Myoporum contains around ten native Australian species (although there have been substantial changes in the classification over time). Overall there are 30 species in the genus, which extends to New Zealand, New Guinea, the Philippines, the Marianas and Bonin Island groups – as well as the Pacific Islands (Hawaii, New Caledonia, Cook and Austral Island groups). There is one species found in the Indian Ocean (Mauritius and Rodriguez Islands). Robert Brown initiated a major step forward in taxonomic classification of these native plants with the discovery of 13 new native Myoporum species from Western Australia and South Australia in 1810 – as well as introducing the genera Eremophila, Pholidia and Stenochilus. Between 1858 and 1885 Baron von Mueller was to make an even more massive

contribution to these botanical studies with 53 new Myoporaceae species (and three new genera). He eventually settled on Eremophila and Myoporum as the two main Australian genera (with seven component ‘sections’) – although over the following century there was to be plenty of debate about the placement of species in different genera (Chinnock 2007). For botanical purposes, the Eremophila genus remains composed of a number of sections – and the early names Pholidia and Stenochilus refer to two of these. Eremophila maculata is placed in section Stenochilus, while Eremophila scoparia belongs to section Pholidia. Disoon is a section in the genus Myoporum. The vast majority of Eremophila are native to Western Australia (over 200 species) and characterised by a very high rate of endemism, with around 80 per cent of those 200-odd being found only in that state.

The Silver Emu-bush, Eremophila scoparia, is a widespread species, ranging from Western Australia, across the continent to New South Wales, extending to South Australia and Victoria. It was originally named Pholidia scoparia by Robert Brown (1810). (Image courtesy Melburnian)


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Bastard Sandalwood: Fragrance from the Desert

Tar Bush, Eremophila glabra, was formerly classified as Stenochilus glaber by Robert Brown (1810). There are around 10 subspecies of this plant, which is very popular as a garden ornamental – this is the cultivar ‘Murchison Magic’. (Image courtesy Melburnian)

A few closely related species in family Myoporaceae have a restricted distribution in south-western Western Australia: • Calamphoreus inflatus (formerly Eremophila inflata) is classified as rare from the Roe and Eyre botanical districts. Glycocystis beckeri (formerly Eremophila beckeri) has a similar distribution. • Diocirea is a genus of four species (D. acutifolia, D. microphylla, D. ternata, D. violacea) that is found in the Coolgardie Botanic District. These plants share features found in both Eremophila and Myoporum, forming a botanical link between these genera. Overseas links: • Bontia contains a single species (B. daphnoides) that is restricted to the Caribbean Islands and the adjacent coast of Venezuela and Guyana. This species has important historical links because it was the first of the family to be described botanically, listed in Linnaeus’ Species Plantarum in 1753 – although samples had been collected and shipped to England prior to this in the late 1600s and early 1700s. • Pentacoelium contains a single species (P. bontioides) that is found in southern China and Japan.

The Bastard Sandalwood (Eremophila mitchellii) is a highly resilient shrub or small tree that is capable of regenerating from its roots. This enables it to withstand drought, fire, ringbarking or even being cut down. In some parts of Australia it has shown an invasive tendancy that has seen it acquire a weedy status. (Image courtesy Russell Cumming)

On his second expedition Ludwig Leichhardt set out from the Darling Downs seeking the west coast, and covered 800 kilometres before being forced to return due to heavy rain, malarial fevers and severe supply shortages. On this journey he noticed ‘a white Vitex in full blossom’ (11 December 1846). Daniel Bunce, the botanist of the party5, described the same tree from around Chinchilla (5 January 1847): ‘another very handsome pyramidal-growing tree, which we called white Vitex. The leaves were of a lively green, and when rubbed, emitted a strong bitter smell’. Roderick John Fensham (Queensland Herbarium) notes: ‘These descriptions are compatible with Eremophila mitchellii [pictured here]. The flower shape of E. mitchellii is similar to the widely cultivated European species Vitex agnuscastus. Furthermore E. mitchellii has a current distribution matching the geographic spread of Leichhardt’s numerous records of “Vitex”, and it is a common species not otherwise described by Leichhardt.’ (Image courtesy Ian Sutton) 5 Bunce was an accomplished author who published numerous articles and books on gardening and the native flora, as well as an account of his travels with Leichhardt. He also studied and recorded Aboriginal languages intensively. He was the first director of the Geelong Botanic Gardens (appointed 1857, died 1872).

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The highly fragrant timber of Eremophila mitchellii resulted in the tree gaining a reputation as a ‘Bastard Sandalwood’: ‘Mr. R. H. Cambage points out that it is sometimes called Sandalwood from the fragrance of the wood, but that it is not to be confused with the Sandalwood of Western Australia, Santalum cygnorum [S. spicatum]. It is sometimes sent in as Rosewood, a name it shares with other small western trees’ (Maiden 1921b). The aromatic qualities of Eremophila mitchellii inspired the production of an essential oil, which continues to be marketed today. The oil is steamdistilled from the wood and bark of the tree, and contains eremophilone (30–60%) as the predominant compound, with variable amounts of 2-hydroxyeremophilone (6–25%) and 2-hydroxy2-dihydroeremophilone (11–30%). The oil has mild analgesic attributes, which has made it a useful additive to massage oils for the relief of sore muscles and joints. It has good fixative and balsamic attributes and can impart a desirable woody aromatic quality to men’s toiletries (www.aromaticplantproject.com specification sheets for Australian essential oils). Furthermore, studies have indicated antimicrobial properties of interest. Undiluted, the oil showed inhibition against Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, Alcaligenes faecalis and Candida albicans, although it was inactive against Pseudomonas aeruginosa. Diluted (1%) the oil was still active against Salmonella typhimurium (Wilkinson & Cavanagh 2005).

Eremophila mitchellii: cut logs and standing timber. (Images courtesy BioProspect Limited)

Fencing requires extremely durable timbers such as that from the Bastard Sandalwood. (Courtesy BioProspect Ltd)

Eremophila mitchellii yields a useful timber resource and Joseph Maiden specifically mentioned its deployment for fencing purposes:

Red Sandalwood oil, from Eremophila mitchellii. This wood oil primarily contains eremophilone – as well as eremophiladienones and santalcamphor, all of which have active termicidal properties (Beattie 2009). (Image courtesy Jeanne Rose Aromatherapy)

In heavy black soil, it is preferable, in my opinion, even to Ironbark, though it does not make such an attractive and solid appearing fence, for the reason that it is so light. In heavy black clayey soil it is well known that a heavy fence soon gets out of line, its own weight tending to pull it over, one way or the other as the ground gives. At

ARID LANDSCAPES: MEDICINALS AND AROMATICS FROM THE DESERT the same time it may be claimed for it that it will last in the ground, despite its small size, as long as the best of Ironbark. In fact, its sole disadvantages appear to be its small size and its comparative scarcity. It is not a fodder tree. It is easily destroyed by ringbarking, and when dry supplies excellent fuel, which on being burnt gives off a very sweet odour, one that strangely enough seems more powerful at a distance than when close at hand. I have frequently, when walking down the street, smelt buddha burning in someone’s kitchen fire some chains away. This fragrance is always in the wood, green or dry, and is as strong as that of Myall [Acacia pendula], though it differs slightly in perfume. It has a deep brown heartwood and yellow sapwood, polishes readily and should be a good cabinet timber where small sizes only are required. Apart from its utility, it is a handsome little tree, generally well shaped, with graceful light green foliage, and in spring bears a wealth of beautiful and sweet-scented blossom. It grows usually on sand ridges and most frequently in conjunction with round-leaved Box, Eucalyptus populifolia, when it is considered to indicate shallow ground with a clayey subsoil (Maiden 1921b).

Bastard Sandalwood has long been reputed to have insect repellent properties: ‘Mr. Baker gives its hardness as “very hard” … and recommends it for veneers. Owing to a strong aromatic odour, resembling that of sandalwood, furniture made of this timber is said to be free from the attacks of insects, according to the late Mr. Thozet, of Rockhampton, Queensland’ (Maiden 1921b). However, the Reverend TenisonWoods (1882) remained unconvinced: ‘It is said that this wood will keep away the Blatta, or cockroach. I cannot confirm this statement. I had a good-sized billet cut and planed, and the odour from it was so strong as to perfume one of my trunks in which it was placed, but the cockroaches treated it with the utmost disdain. They ran over it and laid their eggs under it, just as if it had been put there for their accommodation.’ It was noted that rabbits were rather fond of the tree for fodder (although it was not considered suitable as a stock feed), which led to the use of the twigs in combination with strychnine baits for pest elimination programs.

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A Matter of Identification The Government Gazette of 9 October 1889 published the following with regard to the preservation of Australian Sandalwood stocks: ‘Notice is hereby given that … the cutting of the Sandalwood tree within 5 miles of the Darling River, and within 5 miles of the Murray, below the junction of the Murrumbidgee River, is prohibited. When in time of drought this tree is required for feed, the lighter branches only should be lopped’ (Henry Parkes, Member of Parliament). However, there was some confusion with regard to the identity of the tree concerned. The matter was taken up by the press, which led to the following ‘sensible letter’ in the Sydney Mail of 14 June 1890: Something has been said recently of Sandalwood as a sheep food. I would state that the tree known as sandalwood on the Darling and in the West generally, one of the Eremophilas called ‘Budtha’ by the natives, is not eaten by sheep, and is only attacked by rabbits when nothing better is to be had. During the droughts of the last nine years our sheep have never touched this shrub. The ‘Quandong’ Santalum acuminatum is good sheep food, but is not plentiful enough to be made much use of, and is not known by the name of Sandalwood. I would suggest that all Government notices referring to this plant should give the botanical names of such as well as the (supposed) popular names, in order that the plant indicated may be identified. There are numbers of plants which in one district carry the same names by which in another quite a different plant is known (author not noted, from Maiden 1921b).

Although this appeared to be a logical suggestion, Maiden pointed out that: ‘The matter is not without difficulty, for ours is still a young country, and the botanists are few, often carrying out their work under great difficulties’. Surprisingly, in some remote regions of the continent these comments could be equally true today.

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Investigations have established that there exists considerable variation in the active components of essential oil samples distilled from different parts of Eremophila mitchellii (Beattie 2011): • Heartwood (yield 2.2%) and root (yield 0.3%): oil samples were much higher in eremophilone (43% and 41% respectively), as well as containing santalcamphor (17.5% and 4.4% respectively). These oils were distinguished by an eremophiladienone (18%) in the heartwood and sesquithuriferone (43%) in the root oils. • Branchlet samples (low yield: 0.04%): low levels of eremophilone (5%), with a higher level of spathulenol (16%). Globulol (6%) and aromadendrene (3%) were also present. • The fragrant leaf oil is chemically distinct from the root or wood oils, and has demonstrated significant cytotoxic activity.6 Leaf oil (yield 1.4%): ɑ-pinene (23%) and spathulenol (10.5%), with small amounts of globulol (4.5%), viridiflorol (3%) and viridiflorene (3.6%). Eremophilone was not present. • An unnamed sesquiterpene was also present in oils from the leaf (10%) and branchlets (12%). Early investigations showed that the wood oil was relatively non-toxic as a fly spray – however, when combined with pyrethrins there was a substantial synergistic effect. This resulted in a marked increase in mortality of the flies in comparison to the use of pyrethrin alone (Kerr 1951). There has been a resurgence of interest in Eremophila wood oil due to its insecticidal and termicidal properties. It has potential for use as a fumigant in chemical soil barriers – as well as for timber treatment and preservation. The main active components of interest are eremophilone and its derivatives – leading to the development of a special oil formulation (Termilone) that was successfully trialled and subsequently entered the marketplace (Beattie 2011; Leach 2004). 6 A number of other species have shown cytotoxic activity: E. dempsteri, E. deserti (syn. Myoporum deserti), E. gibbosa, E. ionantha, E. miniata, E. racemosa, E. scoparia and E. subfloccosa subsp. subfloccosa were among the species considered worthy of further investigation (see Beattie 2009). 7 See also page 329.

Extracts of the Asian shrub Myoporum bontioides have shown activity against the crop pest Diamondback moth (Plutella xylostella), which dines on cruciferous vegetables (broccoli, cabbage, Brussels sprouts, cauliflower etc.). The essential oil contains the repellent compound myoporone (which is present in a number of native Eremophila species) that is active against this moth (Gu 2004; He 2004). (Image courtesy plj.johnny, flickr)

Ligularia macrophylla, native to the Caucasus and the Altai Mountains (Central Asia). Eremophilones are present in other herbs, including some the Daisy family (Asteraceae7). Chinese studies have determined that a number of Ligularia species contain eremophilane components (Nagano 2012). Indeed, an eremophilane from Ligularia macrophylla demonstrated activity against the Formosan subterranean termite (Coptotermes formosanus) (Cantrell 2007). (Image courtesy Station Alpine Joseph Fourier)


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Termite Mounds: Underpinning Ecosystems

The Formosan subterranean termite (Coptotermes formosanus) is a pest species native to Japan, Taiwan and China – although it now has an international distribution, being found from southern Africa to the US mainland and Hawaii. This highly destructive species, which can breed quickly, is often used in testing systems for termicidal agents. Cabrera (2005) noted: ‘Like many other termites, the Formosan termite feeds on wood and other materials that contain cellulose, such as paper and cardboard. Bacteria and other single-celled organisms live in the termite digestive system and digest cellulose providing nutrition and energy for these termites. Although they feed mostly on wood, they will eat other cellulose-containing materials such as cardboard and paper. However, they are known to chew through foam insulation boards, thin lead and copper sheeting, plaster, asphalt, and some plastics’ – although, apparently, the notion that they eat concrete is a myth. The Australian ‘Masto’ (Mastotermes darwiniensis) has an equally destructive reputation. The lower picture shows termites tagged with traceable proteins that allow researchers to track the movements of the insect. (Images courtesy US Department of Agriculture, Agricultural Research Service)

A specimen of Eucalyptus pellita that has been eaten through by termites, and a branch showing old termite activity. Some termite species of the grasslands, such as Coptotermes acinaciformis, build nests against living trees and eat the tree from within. For this reason they are known as ‘pipingtermites’. These hollowed branches from various Eucalypts are harvested for making didgeridoos.

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In some parts of Australia termite mounds can reach gigantic proportions. While most would regard them as a horrifying spectre in residential areas, these small insects have a significant environmental impact. The Magnetic Termites (Amitermes meridionalis and A. laurentis) and the Cathedral Termite (Nasutitermes triodiae) are the species that build gigantic mound nests.

Termites, despite the fact that they are often called ‘white ants’, are ancient insects more closely allied to cockroaches and wasps than to ants. Their origins, around 130–150 million years ago, pre-date those of other social insects such as bees and ants by millions of years. Of the 350 (or so) native species, however,

The arboreal termite (e.g. Nasutitermes graveolus) runs covered highway tracks down the trees for access. (Images courtesy Heather Rabbich)

only around 20 are nuisance wood-eating pests. The Masto (Mastotermes darwiniensis) of the northern tropics has earned a quite infamous reputation as an indiscriminate ravenous pest. Considered by some to be the world’s most primitive living termite – the last of its line – this ancient survivor is a voracious nuisance in urban settlements, an environment in which it thrives. Large colonies can contain over a million insects, with their subterranean lodgings


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covering several hectares of land – a disaster just waiting to happen if new developments disturb their environment. The Masto can eat just about anything, not just limiting itself to houses and crops – car tyres, electric and telephone cables, bitumen, rubber and PVC pipes are all on the menu.

Mastotermes darwiniensis. (Courtesy CSIRO)

It is extremely fortunate that the remaining 95 per cent of the native species are much less offensive. These termites often have a vital environmental role upon which entire ecosystems are based, particularly in the savannah wilderness. According to Andersen and Jacklyn (1993) they can be considered ‘the lifeblood of Top End (northern tropics) ecosystems. Savannah ecologists believe that a combination of exceptionally infertile soils and highly seasonal rainfall means that the Top End is incapable of supporting the vast populations of mammals so characteristic of some African savannahs. Thus insects reign supreme in this part of the world, and are the driving forces in ecosystem dynamics.’ Termite communities are not only a source of food for a diverse range of animals, as they also provide all-important shelter and nesting sites.

Numbat (Myrmecobius fasciatus). Upper illustration from John Gould, FRS, Mammals of Australia, Vol. I, Plate 52, London, 1863. The Numbat is a native Australian species that feeds exclusively on termites, around 20,000 per day. Numbat populations have suffered badly from introduced predatory species, notably the Fox. Indeed, the animal was almost consigned to extinction – with the total population dwindling to less than a thousand in the 1970s. It is still considered to be at risk and is listed as an endangered species. (Image above courtesy Helen Ensikat)

Soils in Australia’s arid and semi-arid lands, which are naturally devoid of earthworms, tend to become compacted and hardened without insect-induced aeration. Mismanagement of land resources due to overgrazing, inappropriate land-clearing practices, and mining operations, has compounded the problem across the country. Despite their overwhelmingly poor press, many species of termite perform essential recycling functions that help degraded lands recover. Their tunnelling and nesting habits permit air and water circulation into the deeper soil layers, thereby limiting water evaporation, particularly in arid situations. They also enrich the soil with woodcomposted droppings (O’Neill 2002; Andersen & Jacklyn 1993).

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Some termites collect up to 60 per cent of the local grasses, woody material and annual leaf fall to construct fungus gardens within their nests – which means around 1.5 tonnes of litter is removed per hectare on a yearly basis. This rather remarkable natural ground-level clean-up and recycling operation has invaluable consequences for soil fertility. It also dramatically reduces the flammable fuel load in the forest and ensures that the nutritional resources are preserved, even after a fire has occurred (Sileshi 2009). Indeed, ‘Termites are the premier decomposer insects – along with microorganisms they unlock the energy and nutrients contained in dead plant material, which can then be circulated throughout the ecosystem’ (Andersen & Jacklyn 1993). Termites thus play an influential role in the availability of nutrients and water for vegetation (including farmed crops) – and, as their nests are gradually eroded by wind and rain, they become virtual fertile ‘hot spots’ in an impoverished landscape (Andersen & Jacklyn 1993). In some regions of Africa, crops are planted around termite mounds to take advantage of these effects, and sometimes the mound itself is utilised as a fertilising agent (Sileshi 2009). Without these industrious little insects much of the landscape would degenerate further, with the spectre of arid wastelands extending across the continent. Many termite control agents are toxic. The use of arsenic in termiticides, although now banned, has left residual amounts of this toxin in many urban areas. The fact that arsenic can leach into the watertable compounds its undesirable environmental effects. Alternative toxins such as organochlorides (which are classed as persistent organic pollutants) have equally detrimental consequences. There is a need to properly evaluate the threat from individual termite species – and find solutions that do not destroy the local environment: ‘Control practices are usually initiated on anecdotal information rather than on sound scientific inquiry into the biology of the local termite species or their true impact on crops or trees in Africa. None of the entomological literature in Africa provides any empirical data on the social, ecological, or economic risks and trade-offs of control practices. The impacts of chemical control on human welfare and the environment have also been largely ignored or perceived as localised problems’ (Sileshi 2009). To date, these words could be equally

Termite nests in the savannah country of Cape York Peninsula. The impressive mounds of magnetic termites are built using a genetic predisposition for a north-facing magnetic basis – with modifications being made to adjust to different sites. This is designed to create a temperaturestable environment. Maximum sun exposure is desirable on the eastern face in the morning, which will keep the mound warm even after this side passes into the afternoon shade. The design of the mound ensures that it will withstand unfavourable weather conditions (extremes of temperature, exposure to torrential rains and wind) and provide a refuge during seasons when the site is water-inundated. (Images courtesy Katrin Holmsten, www.cape-york-australia.com)

In contrast to the large constructions of magnetic termites, low dome-shaped mounds are characteristic of ‘harvester termites’ (genus Drepanotermes).


true in numerous Australian urban areas. There are considerable risks associated with the use of chemicals for termite control – their use by inexperienced individuals without protective equipment not least among them. In some countries the contamination of edible termite mounds and their associated fungi can result in direct poisoning. Children playing in urban or agricultural areas with residual pesticide contamination can be at considerable risk of poisoning long after the use of pesticides or insecticides has been forgotten.

Termite Mushrooms: An Ancient Association

The Termite Mushroom, Termitomyces reticulatus, from Namibia. (Image courtesy Candice Zimny, February 2008, Namibia)

Display of common household pesticides at Herberton Historical Village, north Queensland. (Courtesy Tony Young).

The literature is fairly sparse with regard to pharmacological investigations of the value of termites – although a few extremely interesting reports exist regarding their antimicrobial potential. Antifungal and antibacterial peptides (e.g. spinigerin, termicin) have been isolated from an Indian termite (Pseudocanthotermes spiniger) (Coutinho 2009). Antimicrobial peptides from Australian termites (genus Nasutitermes) have similar potential (Bulmer & Crozier 2006, 2004). Brazilian studies of the synergistic effect of an extract of the termite Nasutitermes corniger with antibiotics (gentamycin, neomycin and kanamycin) against drug-resistant strains of Escherichia coli bacteria showed good activity. This suggests that a combination of a termite extract with various antibiotics could enhance the drugs’ antibacterial efficacy. However, variations in activity could be associated with the source of the termites – with the tree from which they were harvested influencing their antibacterial properties (Coutinho 2009).

Fungi are associated with a wide variety of termite mounds, some of which are deliberately cultivated for food – as well as having an important ecological role, with the fungi helping to extract nutrient elements from the termite nest, making them bioavailable to the surrounding vegetation (Spain 1998). The termites practising this intriguing form of ‘fungiculture’ (farmed fungus gardens) usually propagate species of Termitomyces. The crop, on which they are dependent, is fertilised with their own droppings (faecal pellets). The fungal spores pass through the insects’ intestines intact – thereby automatically supplying a new generation of fungal supplies for the garden. Interestingly, some of these fungi contain a xylanase enzyme that has useful potential as a biobleaching agent in the paper and pulp industry (Faulet 2006). Other suggestions for the use of serine protease enzymes8, primarily sourced from Termitomyces albuminosus, include industrial applications such as detergents, brewing and leather production (Zheng 2011). Medicinally, 8 While we know little regarding the value of these compounds in Termitomyces mushrooms, proteases can play an important role in cellular metabolic processes. They are of interest for medicinal and chemical applications, food processing, animal feed, and for industrial purposes such as silver recovery and waste treatment (Zheng 2011; Kitts & Weiler 2003).

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extracts of this fungal species have demonstrated anti-inflammatory and analgesic properties, which were attributed to saponins and polysaccharides (Lu 2008). Various species of Termitomyces (there are 30 in the genus) have been regularly harvested on a local basis in Africa, Southeast Asia and India. This is of interest because some mushrooms have cholesterol-lowering potential – including Termitomyces microcarpus from Uganda and T. eurirrhizus from Indonesia (Mursito 2010; Nabubuya 2010). Investigations of various mushrooms (particularly a polysaccharide component) have also attracted interest as potential anticancer (antiproliferative) and immunostimulant agents. This includes Termitomyces – for example, T. clypeatus from India (Maiti 2008). Other Indian species such as Termitomyces heimii and T. mummiformis have significant antioxidant potential that is linked to phenolic components such as tannic acid, gallic acid, protocatachuic acid and gentisic acid (Puttaraju 2006).

Precious Resources

The Bastard Sandalwood is not the only fragrant representative of the arid flora with useful environmental attributes. The Desert Whitewood is another tree considered to be a precious resource in this challenging environment. Tenison-Woods observed:

Desert Whitewood, Atalaya hemiglauca. (Upper image courtesy Ethel Aardvark, Wikipedia; lower image courtesy Craig Nieminski)

Atalaya hemiglauca, a member of the Sapindaceae is another widely spread inhabitant of the desert regions and a constant accompaniment of the Brigalow scrubs. I believe it was found abundantly in Central Australia and is included in Baron von Mueller’s list of plants brought by Forrest from North-western Australia. It is an abnormal member of the Sapindaceous tribe, with emaciated looking pinnate leaves, but the pinnae [leaflets] are long and so far apart as scarcely to be recognised as such. I have already remarked ... how beautifully fragrant are the graceful clusters of its small white flowers, and how in the desert it is a tree which may be easily known by the multitude of insects it attracts in flowering time. Afterwards it is equally conspicuous from the abundance of small yellow, winged seeds. These are like the sycamore except that they are not in pairs. The wood is very hard but the trees are always too small to be of much use.

Whitewood is an important drought-resistant and fire-tolerant feature of the desert landscape. It harbours witchetty grubs and an edible white sap (Latz 1996). However, Joseph Maiden noted that: ‘Most of this gum is quite colourless … A very small quantity only was received. It is readily soluble in cold water, from which solution alcohol throws down a white precipitate readily soluble in water but insoluble in alcohol, and resembling arabin [arabic acid] in its properties. It is pure gum, and appears to differ little from the purest gum Arabic … This gum would be a valuable article of commerce if obtainable in quantity’ (Maiden 1904). Under ‘Propagation’, Maiden made an interesting comment regarding conservation issues: ‘This is a


Boomerang 1951, made by Lake Tyers Aborigines and sent to: ‘The Prime Minister of Australia, for delivery by Commonwealth jubilee celebrations cyclist-courier to ... Federal Parliament House, Canberra, Australia’. Desert Whitewood timber was noted as being hard and dense, suitable for making nulla-nullas at Elliott (Kulumindini) and different types of boomerangs at Daguragu in the Northern Territory. It is also a useful firewood (Wightman 1994, 1992a). However, Latz comments that a soft timber from the same species is used for making ceremonial ornaments in Central Australia (Latz 1996).

useful tree, and is one thoroughly acclimatised to the droughty conditions of the West. It is one, therefore, that should be conserved wherever possible, and should be resown wherever the expenditure will admit of it. I feel strongly that in any measure of “reafforestation” (and our efforts in the West must be on a modest scale) preference should be given to such of our native shrubs and trees as are both useful and drought-resisting’ (Maiden 1904). In addition, young roots of the related Atalaya variifolia (a tree also known as Whitewood) have been eaten raw, or roasted in a campfire. The older roots were too fibrous to be of any culinary value (Hiddins 2001). Desert Whitewood has been extensively utilised for fodder, although concerns have been expressed about the toxicity of the young shoots and the seeds. Feeding tests established that the fruit was extremely toxic to horses – although the risk of poisoning, the compounds responsible, and the mechanism of toxicity for other animals (sheep, cattle) has been highly debated. Whitewood belongs to the Sapindaceae family and contains haemolytic saponins that are toxic to fish and snails, but their involvement in animal poisoning would be unlikely (Everist 1981). Investigations by the CSIRO found that plant extracts (leaf and stems) contained alkaloids, with a weak hypotensive effect (Collins 1990). In an arid landscape, the Desert Whitewood as a prolific flowering tree would be greatly sought after

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When the Desert Whitewood flowers it is a sign that the Freshwater Crocodile is laying eggs that could be collected. These were a favoured food resource. When the tree ceases flowering, the baby crocodiles are hatching (Wightman 1992b).

by all types of insects – as Maiden commented: ‘Mr. Froggatt tells me that this profuse flowerer will always be an important plant in the west for any bee-keeper. He informs me that it is specially attractive to the native bees; it is a perfect collecting ground for them’ (Maiden 1920). Aboriginal people harvest ‘sugarbag’ (native honey) from the tree – which is not only a honey resource, but also provides pollen and wax (Marrfurra 1995). Wild hives of the honey bee (Apis mellifera), which are now found across the Australian continent, have become equally prized.

Beehive in tree. (Courtesy Bilby, Wikimedia Commons, CC-by-SA 3.0 Unported)

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Blue Banded Bee, Amegilla cingulata (left) and Cuckoo Bee, Thyreus sp. (right). There are around 1600 species of native Australian bees, many of which are colourful pollinators and all of which are stingless. They include the Blue Banded Bee (one of 25 species in the genus Amegilla) – which visits greenhouse tomato plants (up to 1200 tomato flowers per day) and has potential as a pollinator for various other crops such as eggplants, blueberries and chilli. Stingless bees also appear useful for crops such as macadamia, watermelon, lychee, mango, strawberries, citrus and avocado (see www. aussiebee.com.au/croppollination; Hogendoorn 2010). The Cuckoo Bee is another intriguing native, which lays its eggs in the nests of other bees, including that of the Blue Banded Bee. (Images courtesy Susan McBratney)

Manna from the Desert The Sugarwood has lived up to the reputation of its common name since the early days of the Australian colony. Joseph Maiden commented that Myoporum-manna was ‘a perfect substitute of its European namesake, and when freshly exuded its colour is not objectionable’. Pastoralist and amateur naturalist KL Bennett, ‘whose knowledge of such matters was both extensive and accurate’, provided greater detail: During the hot summer months another and totally different substance exudes from the trunks and branches of some of these trees in large quantities. This substance when freshly exuding from the tree resembles a thick froth, either pure white, and resembling snow, or of a pink or rose colour. These exudations assume various forms, and become solidified by exposure to a certain extent to the air. Sometimes they are in lumps as large as a man’s hand, and sometimes in the form of stalactites over a foot long, as large as an ordinary candle, and gradually tapering to a point.

Sugarwood or Red Sandalwood (Myoporum platycarpum). (Images courtesy Rusell Dahms, flickr) This substance is of a highly saccharine nature, with a peculiar sickly sweetness; it melts in the mouth like ordinary sugar; the natives are very fond of it, and either eat it, or by dissolving it in water make a kind of drink (quoted in Maiden 1892–96).

An analysis of the manna isolated a crystalline substance, which was identified as ‘mannite’ (mannitol).9 However, Maiden also commented: In spite of its sweetness, Fr. Helms informs me, that the natives were not partial to it, preferring the gum of Acacia leiophylla, probably because of its laxative property, and not from any objection to its sweetness, inasmuch as the blacks eat lerp and Eucalyptus mannas, honey stored by bees, and also suck the honey-laden flowers of certain plants. It will be remembered that Sir Thomas Mitchell offered sugar to an aboriginal child who spat it out 9 Similar to the Australian Sugarwood, the leaves of Ngaio (Myoporum laetum) contain mannitol. Manna and mannitol are discussed in detail in Volume 1.


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with every manifestation of disgust, but the blacks usually do so with any edible to which they are unaccustomed (Maiden 1892–96).

Sugarwood was not only utilised as a manna resource, it also yielded a gum-resin – with regard to which a collection note of September 1891 commented: ‘This gum was collected partly off a small tree 20 feet high, and four inches in diameter, and is the one on which I noticed gum oozing out, and partly from under it. The tree had been bleeding profusely, and for a long time, as there was a great deal of decaying gum (manna) round the trunk. I believe the cause of bleeding to be insectborers, but had not sufficient time to examine it closely, as my camel was very restive. The taste is sweet as sugar’ (Maiden 1892–96). Maiden later examined the gum-resin in greater detail: ‘[it] is used by the aboriginals as a substitute for pitch and wax … they use it alone, or mixed with fat, to cement the stone heads of their tomahawks to the fibre which joins them to the stick forming the handle … it forms a natural sealing wax, and is sometimes used by the people of the interior for this purpose’. While he considered that it could be suitable for use as a sealing wax ingredient, it was too soft to be utilised alone. Fresh, it was a hard, brittle substance that broke ‘with a glassy fracture which is at first of a purple or indigo colour, but becomes brown upon keeping … It softens even with the warmth of the hand, and if kept in a bottle, the heat of an average day is sufficient to fuse pieces’ (Maiden 1889b).

A Poisonous Mystery

In 1880 Frederick Manson Bailey drew attention to the toxic potential of ‘a small shrub of Myoporineae, called Eremophila maculata, or Native Fuchsia, which is regarded as a poison bush by some graziers, although others consider it quite harmless and with others of the genus, good fodder bushes. The plant bears a profusion of handsome red and yellow flowers, which should recommend it for garden culture and

Eremophila maculata has three subspecies: brevifolia, filifolia and maculata. The latter is the most widespread, ranging from central western Australia across the continent to the east coast, although it is not common in Victoria. It also has the greatest range of flower colour, spotting, leaf shape and degree of hairiness on branches. Subspecies filifolia has a highly restricted distribution in the Pilbara region of Western Australia – subspecies brevifolia is more widespread in Western Australia, extending into central Australia. (Images courtesy Stan Shebs)

as there seems a doubt of its properties it would be well to have it examined for medicinal purposes.’ The shrub was classified as a stock poison in 1887, but the reason for its effects remained a mystery for quite a long time. Joseph Maiden (1921a) mentioned these reports were ‘made in the days before we knew anything of cyanogenetic glucosides’, the latter being

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identified as the toxic components. The plant showed a puzzling picture of toxicity: ‘It does not appear to be dangerous to stock accustomed to eat it, but to others, travelling stock particularly, Mr. Hutchinson, of Warrego (Q.), considers it to be deadly. The effects of this plant are always worst after rain. It appears to be most dangerous when in fruit (Bailey and Gordon).’

are under conditions of stress, even though, as Turner observed, they are often eaten quite safely by animals grazing quietly in the paddock.’ All the cases of poisoning in sheep or cattle were linked to stressful conditions when the animals were hungry or being driven. A few cases of fatal poisoning

Maiden provided further details: The following reports were published by me in the Agricultural Gazette of New South Wales during the year 1898:– The Stock Inspector from Bourke district reports that a large number of travelling sheep died from eating fuchsia bush in the Bourke district. The sheep were in good condition, and not hungry. After having watered them, of those that ate the plant some 300 died, fifty of them almost immediately, the remainder in three hours afterwards. He opened several of the sheep, and found that the last food they had eaten was this fuchsia bush. In the reply sent to the Inspector it was suggested that the sheep might have died from hoven [bloat], and that I was not aware that a toxic principle had ever been extracted from the natural order of plants to which it belongs. Shortly afterwards the Inspector of Stock, Hungerford, northwest of Bourke, reported that a number of cattle had been poisoned when travelling over the country where the plant grows, which only seems to poison stock in the winter.

However, experimental evidence did not corroborate their suspicions: ‘Mr T. W. Mackie, Inspector of Stock for Hungerford, wrote to the Chief Inspector of Stock stating that he had made a thorough trial of the plant Eremophila maculata on two sheep, which were starved for ninety-six hours before the plant was given them to eat. They ate the plant, and were then held in the pen for thirty-six hours, but the plant did not seem to have any bad effect on them, so they were turned out.’ The first papers on the cyanogenetic potential of this species appeared just over a decade later. In 1910, JC Brünnich and F Smith published an article on the poisonous principle of Native Fuchsia (Eremophila maculata) (cited in Maiden 1921a). In 1914 Smith reported on the cyanogenetic glucoside of Eremophila maculata (cited in Maiden 1921a). Over time, the problem became very familiar, with Selwyn Everist (1981a) commenting, ‘It has since been well established that the shrubs in question, mainly Myoporum spp and Eremophila maculata, are frequent causes of intoxication in sheep and cattle that are unaccustomed to them or

Eremophila maculata ‘Aurea’. Eremophila maculata shrubs, which bloom year round, have a wonderfully variable range of flower colours. In the subspecies brevifolia red, pink, orange, yellow and white flowering shrubs can all be found within a single population. Subspecies maculata tends towards red, orange, yellow and pink flowers.


occurred in sheep that had eaten large amounts of wet Fuchsia Bush after a period of semi-starvation. The symptoms (muscle trembling, accelerated pulse, deep breathing, difficulty breathing, gasping, staggering) sometimes resulted in convulsions, paralysis, prostration, coma and eventual death. This was ‘consistent with the known effects of HCN [hydrocyanide, aka prussic acid] in producing asphyxiation at cellular level. In the field animals usually die very rapidly, and are often found dead without any symptoms being observed’ (Everist 1981b). The following note on Eremophila maculata summarises its contradictory toxicology: ‘[it is one] of the most strongly cyanogenetic plants known and as little as 30g of leaf will kill a sheep; however stock seem to eat it with impunity in normal grazing situations’ (www.florabank.org.au). The discovery of the cyanogenic toxin prunasin provided the solution. This compound is broken down by tissue enzymes when the plant is damaged, permitting the release of HCN. Immature leaves less than eight weeks old (particularly after summer rains) were discovered to be more problematic because they contained fairly high amounts of the toxin. There was, however, a complicating factor. The variation in toxicity was eventually linked to a catalytic enzyme that allowed the toxic reaction to proceed in the plant. Variability in the levels of this enzyme could therefore significantly influence the poisonous effects of the plant (Dowling & McKenzie 1993). Eremophila latrobei was identified as another toxic species, with feeding tests showing poisoning in sheep and goats. This was characterised by movement

disorders (staggering, pronounced drooping of head, swaying side to side, failure to stand erect, collapsing onto knees, finally lying down) – after which there was progressive development of distress (shallow rapid respiration, gasping, irregular leg movements, hypersensitivity), leading to coma and death due to respiratory failure. Sheep and cattle developed liver dysfunction, and haemorrhages occurred throughout the body (gastrointestinal tract, heart, and under the skin). The toxic compounds were identified as furanoid sesquiterpenes, primarily ngaione (Everist 1981b).

Eremophila deserti. (Courtesy Paul Campbell, flickr)

The Ellangowan Poison Bush

Warty Fuchsia Bush, Eremophila latrobei. (Courtesy Peter Matthews, flickr)

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Myoporum deserti (now Eremophila deserti), the Ellangowan Poison Bush, is found throughout inland Australia. Like Eremophila latrobei it has been involved in numerous cases of stock poisoning. The toxic components are similar – the furanoid sesquiterpenes ngaione, myodesmone, myoporone and derivatives. The plant also contains non-toxic terpenes (sesquiterpenes, monoterpenes).

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Poisoning incidents usually involved travelling sheep and cattle that had consumed large s amount of the bush at an overnight camp. After travelling 1–3 days without any outward signs of distress, they would suddenly die a few hours later. However, animals grazing quietly in paddock could eat the plant readily without ill effect. The problem was twofold. Under conditions of stress the activity of MMFOs (microsomal mixed function oxidases) in the liver was increased, leading to liver tissue damage. In addition, there was substantial variability in the toxicology of the plant. The biochemistry involved was extremely complex – with at least nine different chemical races being identified: five were toxic, two were non-toxic, and two contained only small amounts of the toxins in their essential oil (Everist 1981).

Sunlit leaf of Ngaio (Myoporum laetum), showing leaf cells that contain ngaione. (Courtesy Avenue, Wikimedia Commons)

Ngaio seedling. The liver toxin ngaione is present in the leaves of the New Zealand Ngaio (Myoporum laetum), therefore, despite the fact that this plant has been utilised medicinally (see page 295), its internal use should be strictly avoided. The fruits, although they tend to be very bitter, have been eaten when ripe – although one would probably be better off avoiding them altogether (Brooker 1993; Crowe 1993). (Image courtesy Tim Hogan)

Desert Herbals

The Showy Eremophila (Eremophila racemosa). This species, which has a restricted distribution in southwest Western Australia, certainly lives up to its name. It was classified as Stenochilus in 1838 by Stephen Endlicher, but von Mueller transferred it to Eremophila in 1859. Leaf extracts contain six major metabolites: prunasin (a cyanogenetic glycoside), luteolin (a flavonoid), phyllygenin (a lignan), phillyrin (a lignan glycoside) and glucosides of pinoresinol and epipinoresinol (Beattie 2009). (Image courtesy Stickpen, Wikimedia Commons)

It would seem rather odd that plants suspected of having poisonous properties could acquire a fairly widespread medicinal reputation, although Eremophila maculata was not deployed to any great extent. A number of Eremophila species were recommended for external use only – a prohibition that was made very clear regarding the use of E. longifolia (see Table 7.1, page 316). There is, however, the consideration that cyanogenetic glycosides are readily detoxified – once catalysed, they are fairly quickly removed during in the preparation process (see Volume 3 for details on cyanogenetic compounds).


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Table 7.1 Summary of the Medicinal Uses of Eremophila Species Eremophila alternifolia Narrow-leaf Fuchsia Bush

Traditional medicinal and cultural uses Low (1990); Isaacs (1994): • Leaves utilised as a remedy for just about everything; may be stored for later use therefore leaves are dried and carried for supplies. • Leaf decoction/infusion: steam inhaled or used as a wash. Richmond & Ghisalberti (1994): • Applied to septic wounds; used as a body wash for fevers. Latz (1996): • Leaves: infusion used as rubbing medicine or sometimes taken internally for various ailments. • Regarded as being a potent medicine that will ‘encourage deep sleep and pleasant dreams’. Goddard & Kalotas (1988): • Highly valued medicinal plant. • Leaves chopped, made into a paste and used as a ‘rubbing medicine’ or made into a poultice (tied in spinifex grass covering) and applied to head for pain relief. Barr (1993): • ‘Eremophila alternifolia is not a common plant; preparations are considered to be potent but safe medicines, the treatment of choice in many illnesses’. Used for everyone and are considered suitable for use by the elderly and young children. • Leafy branches sun-dried and leaves collected: used to make leaf infusion or boiling water poured through leaves in strainer (infuse mixture 1–2 hours and strain) • Treatment for coughs, colds, headache, fever, internal pain: 100 ml mixture taken every few hours. • Fresh leaves: used to make a tea. • Leaf: dried, powdered and made into a paste: applied to body for internal pain and as part of treatment for any severe illness. • Leaf: wash used all over body for serious sickness, coughs, colds, rubbed over affected parts for aches and pains, bronchitis. Note: Sometimes the bark of young twigs (which have a different fragrance) is used similarly. Eremophila Webb (1948): bignoniiflora • Fruit decoction used by Barcoo Aboriginals as a laxative. Richmond & Ghisalberti (1994): • Fruit taken for a purgative effect; leaf decoction laxative. Barr (1993); Wightman (1992a): • NOT suitable for use in babies. • Young leaves decocted as a remedy for fevers, colds and influenza; used as a body wash. • Leaf and twigs softened in decoction and wrapped around the head to alleviate headache associated with nasal congestion and sinusitis. Eremophila cuneifolia Reid & Betts (1977): • Leaves boiled and decoction drunk for colds.

Investigations, essential oil studies Barr (1993): • Leaf essential oil: oil yield 4%; main components: fenchone (44%), limonene (15%), unidentified monoterpene (27%). Note: Fenchone is found in Fennel oil and Absinthe. It has an aroma resembling camphor and has been utilised in the perfumery industry. Ghisalberti (1994a): • Other components: sesquiterpenes and flavonoids. Pennacchio (1995, 1996): • Extracts have shown cardioactive properties.

Ghisalberti (1994a): • Leaf extract: contains mannitol, verbascoside. • Mannitol has a mild laxative effect. It is found in significant amounts in Myoporum platycarpum manna. Beattie (2009): • Methanol extracts also contain quercetin and nepetin.

Ghisalberti (1994b): • Essential oil: spathulenol, β-eudesmol, elemol,10,11-dehydrongaione; other components: myrcene. • Leaf extract: mannitol, verbascoside, geniposidic acid. • Leaf resin: diterpenoid acids.

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Latz (1996): • Alyawarr people consider this plant to have powerful medicinal properties. • Highly aromatic leaves are ground with fat and the resultant ointment rubbed on the upper body and under the nose for the relief of colds and other chest complaints. • Leaves: decoction used as a body wash to cure scabies. Richmond & Ghisalberti (1994): • Leaves used as body rub for chest pain. Eremophila duttonii Latz (1996): Harlequin Fuchsia • Plant considered to have useful medicinal properties. Bush, Red Poverty Ghisalberti (1994a): Bush • Reputed to have insect-repellent properties. (The term ‘Poverty Barr (1993): Bush’ refers to the • Leaf: decoction used as body wash for colds and flu; fact that these trees antiseptic application to infected cuts, scabies, open are often found sores, painful ears and around inflamed eyes growing on poor soils, • Leaf decoction: liquid taken internally for sore throat unsuitable as grazing associated with respiratory tract infection; mixture lands; Bindon 1996). may be warmed and sugar added to improve taste. Use of this preparation results in mild sensation of numbness in mouth and throat. Note: Preparations are very effective but deteriorate with storage. Medicine is safe for children (use lower dose). • Medicinal preparations are highly valued and regularly used in some communities in preference to proprietary products. • Kangaroos frequently break down the shrub and roll in its leaves, perhaps to remove ticks. Richmond & Ghisalberti (1994): • Leaf decoction: antiseptic wash for sores, cuts, colds, influenza, ENT problems incl. sore throat. Eremophila elderi Latz (1996): • Alyawarr people sometimes use this species medicinally. Ghisalberti (1994a); Richmond & Ghisalberti (1994): • Used for cough; used in bedding, head rest for treating colds. Eremophila fraseri Reid & Betts (1977): Turpentine Bush • Aborigines drank decoction of leaves for colds; the plant also believed to cure toothache and rheumatism. Maiden (1889a): • Leaves have a thick resinous coating that was used as sealant and adhesive for cementing spear heads to spear shafts. Bindon (1996): • Waxy resin from leaves: beaten or melted out to form a flattened paddle-shape on ends of trimmed twigs. This was a useful way of transporting the resin or it could be used for trade. Eremophila dalyana

Ghisalberti (1994a): • Plant with restricted distribution. • Essential oil: elemol, eudesmols and cineole. • Leaf extract: complex mixture of lignans.

Barr (1993): • Leaf essential oil: α-pinene (93–95%), limonene (trace–1.2%); α-pinene in another sample was lower (61%). Ghisalberti (1994a): • Essential oil: α-pinene predominant. • Leaf resin: serrulatane diterpenes, flavones. Smith (2007); Barr (1988): • Steam-distilled essential oils: furanosesquiterpenoids (dehydrongaione and dehydroepingaione derivatives) with toxic potential.

Lassak & McCarthy (1992): • Chemistry: active components unknown; plant reported to give strongly positive test for alkaloids; leafy twigs contain resin rich in diterpenoid acids; leaves also contain a flavone and mannitol. Ghisalberti (1994a): • There are several varieties of this species with different chemotaxonomy that is linked to the production of cembranoids or eremanes (with flavones). • Leaf extract: contains mannitol.

ARID LANDSCAPES: MEDICINALS AND AROMATICS FROM THE DESERT Eremophila freelingii Rock Fuchsia Bush, Native Fuchsia, Crimson Fuchsia Bush, Emu-bush

Eremophila gilesii Turkey Bush, Desert Fuchsia Bush

Eremophila goodwinii Purple Fuchsia Bush

Latz (1996): • Important medicinal plant in Central Australia • Leaf decoction drunk or used as a wash for sores and for relief of headaches and chest pains • Leaves may be placed on nasal septum or used as pillow for people suffering colds and other chest complaints. • Inhalations from bruised leaves considered to have healing properties. • Early European settlers used leaves to make a medicinal tea. • Attractive flowers sometimes placed in headbands for decorative purposes during ceremonies. Goddard & Kalotas (1988): • The dried resinous leaves are mashed, mixed with water and the liquid wash rubbed over the body, especially the head. Strong aromatic scent has been compared to Vicks VapoRub. • Smoke treatment (fumigation) of people with body pain and severe coughing (symptoms suggestive of severe influenza or other feverish disorders). Cleland & Johnston (1933): • Used as pillow by Aborigines for ‘sick head’; sometimes placed in perforation of nasal septum. Richmond & Ghisalberti (1994): • Leaf decoction: headache, chest pain, colds; antiseptic wash. Barr (1993): • Medicinal preparations are highly regarded. • Leaf decoction used as a body wash daily for infected cuts and scabies; its regular application to wounds and open sores promotes proper healing. • Leaf placed in bath of hot water: patient is immersed and inhales vapour. This is done daily to reduce fever and relieve congestion of head and chest. • Leaf decoction: taken internally for severe colds and diarrhoea. Turner (1994): • Emu-bush grubs: edible grubs are found on the Emubush. They are easily harvested and cooked before use. Latz (1996): • Similar medicinal uses to Eremophila freelingii. Ghisalberti (1994a); Richmond & Ghisalberti (1994): • Leaves used to make body wash for sores, headache, chest pain; infusions used for treating colds, to promote rest and general well-being. • Dried fine leaves mashed with fat or soaked in water and used as a body rub or as a tea. Cribb & Cribb (1981); Isaacs (1994): • Central Australia: plant used in form of decoction as a wash for body sores, including scabies.

Latz (1996): • Leaf decoction used as a medicinal wash. • However, a more erect form with hairless or almost hairless leaves that has a wider distribution is apparently not used. Ghisalberti (1994a); Richmond & Ghisalberti (1994): • Leaves have purgative properties.

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Ghisalberti (1994a); Lassak & McCarthy (1992): • A sticky shrub with highly aromatic crushed leaves. • Leaves: oil contains various sesquiterpenoid lactones such as eremolactone and freelingyne • Lassak & McCarthy (1992): ‘but whether any of these is medicinally active is not known’. Barr (1993): • Leaf essential oil: α-pinene (69–82%), β-pinene (4–5%), y-elemene (3–4%). Rogers (2000): • Leaf and flower extracts: anti-migraine potential.

Ghisalberti (1994a): • Highly ornamental species. • Contains bisabolene triterpenes. Grice (2003): • Extracts have shown inhibition of platelet aggregation and serotonin-release. • Glycosides: verbascoside and poliumoside isolated. Rogers (2001): • Anti-migraine potential. Note: Cymbopogon ambiguus and Erythrina vespertilio had substantially stronger activity against migraine in this study (Rogers 2001, 2000).

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Eremophila latrobei Native Fuchsia

Latz (1996): • Leaf decoction used as wash for scabies. • Fumes from smouldering leaves to ‘smoke’ babies. • It is possible that the blue-leafed form is preferred for medicinal usage and was given a separate name by Aboriginal people. Latz (1996); Barr (1993): • Sweet nectar found at base of flower is a favoured delicacy. The flower is pulled off the bush and the base sucked to obtain the small amount of nectar. Barr (1993); Isaacs (1994); Richmond & Ghisalberti (1994): • Infusion of crushed leaves: used as a body wash to alleviate chronic malaise and symptoms of colds and flu; leaves may be simply crushed and rubbed over the body for the same purpose. • Leaf decoction/infusion taken in small amounts for cough, sore throat, bad colds; infusion may be simultaneously used as a body wash.

Eremophila longifolia Weeping Emu-bush, Berrigan, Native Plum-tree, Milkwood (Cape York)

Maiden (1921d): ‘Mr. Max Koch informed me that, in the Mount • Lyndhurst district, South Australia, the branches and leaves are used by the blacks to make a bed for the dead.’ Barr (1993): • Leaf medicinal use fresh or dried; plant had significant spiritual importance. • DO NOT take internally, avoid splashing in eyes. • Leaf decoction (crushed leaves decocted with 800– 900 ml water) used as a body wash for treatment of scabies, sores, bites, stings; and to localise boils, relieve aching muscles and joints; applied for headache and chest pains associated with severe flu. • Liniment: crushed leaves mixed with animal fat to make ointment that is massaged into tender, swollen joints or applied over scabies. • Leaves mashed with a little water applied directly to scabies; leaf used similarly as a dressing on boils and carbuncles to encourage discharge of pus. Webb (1969): NSW Bogan tribe: decoction drunk for colds or • applied to sores to promote healing. Latz (1996): • Important medicinal properties. Arandic people use acrid fumes from smouldering leaves to ‘smoke’ mothers and their newborn babies; this is considered to strengthen the baby and stop the mother bleeding. It is also said to increase or initiate mother’s milk supply. • Decoction from crushed leaves: widespread use as eye wash, for treating skin ailments and headaches; used as a general body wash for diverse ailments. • Treatment is said to induce restful and restorative sleep. Isaacs (1994): • Important women’s medicine: smoking medicine – woman lies down with stomach and breasts over pit with smouldering leaves and branches. • Cape York: Milkwood leaves are placed directly on the breast to facilitate milk flow. Note: This herb should be differentiated from the Milkwood tree, Alstonia actinophylla, which contains a milky sap and has been similarly used to promote breast milk production. The sap also has an excellent woundhealing reputation (Webb 1969).

Barr (1993): • Leaf essential oil: α-pinene (16%), guaiol (15%), limonene (8%), terpinenylacetate (6%), β-pinene (4%). • Toxic to goats and sheep in animal feeding experiments. Ghisalberti (1994a): • Leaf essential oil: sesquiterpene furanoids (ngaione, myoporone) and furans. • Leaf resin: contains biflorin, a napthoquinone with antimicrobial activity. Semple (1998): • Stem extracts of E. latrobei subsp. glabra have shown antiviral activity against Ross River virus. Leaf extracts were inactive. Note: Other species of Eremophila were examined in this study and exhibited no antiviral activity – E. duttonii, E. freelingii and E. sturtii. Very weak activity was exhibited by E. longifolia (leaves) and E. alternifolia (stem) extracts. Lassak & McCarthy (1992); Della & Jeffries (1961): • Leaves and bark contain tannins. • Leaves also contain essential oil rich in safrole and methyleugenol. Barr (1993): • Leaf essential oil (low oil yield): α-pinene (50–55%), limonene (17%), β-pinene (4–11%), y-terpinene (1–4%), α-phellandrene (2–4%), sabinene (1–3%). Smith (2010): • NSW arid region samples: three essential oil chemotypes have been established (isomenthone, karahanaenone and borneol). Pennacchio (1996): • Extracts have shown cardioactive properties. Rogers (2000): • Leaf and flower extracts: anti-migraine potential.


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Latz (1996): • The plant has considerable ritual significance for Aboriginal people: ‘it could be said to be the most sacred, mystical or magical of all Central Australian plants’. • Leaves and branches: used extensively in ceremonies, notably for elaborate circumcision rites; foliage used for decoration and to produce an acrid smoke for ritual purposes. • Smoke from leaves used ritually, to blacken artefacts. • Branches: used to line graves and cover bodies. • In the past twigs from Eremophila were placed in headbands, armbands and through nasal septum of returning Arrernte war parties to signify success in killing one or more of the enemy. • A caterpillar with exquisite markings feeds on the leaves of this plant; it is a totemic animal of Arandic peoples as well as being an important food resource • Branches are often used around emu flesh during cooking. • Fruit: favoured food of emus but not considered suitable for human consumption. Eremophila maculata Maiden (1921a): Native Fuchsia, • ‘The aborigines in the Hungerford district, New South Spotted Fuchsia Bush Wales, use the leaves as a blister when suffering from a cold. As it may therefore contain an acrid principle, it might be worth while subjecting it and other species to chemical examination for that substance alone.’ Kielczynski (1997): • Clinical use of E. maculata tincture for the treatment of arthritis; leaf tincture taken internally (1.5–2 ml three times daily), plus E. longifolia: rubbed into joint locally.

Eremophila mitchellii Low (1990): Budda, Budtha, • Timber yields unique smelling aromatic oil, once Bastard Sandalwood used to flavour soap. (although the latter • Aboriginal people of Barwon River used it name is more medicinally. KL Parker mentioned: ‘For rheumatic appropriate for pains a fire is made, Budtha twigs laid on it, a little species of Santalum) water thrown on them; the ashes raked out, a little more water thrown on, then the patient lies on top, his opossum rug spread over him, and thus his body is steamed’. Richmond & Ghisalberti (1994): • Twigs used as general purpose medicine; wood for carvings.

Syah & Ghisalberti (1996); Lassak & McCarthy (1992): • Resin-secreting glands in leaves: whole plant (including fruit and flowers) contains cyanogenic glycoside (prunasin). Ghisalberti (1994a): • Myoporone and an analogue have been isolated from extracts. E. maculata var. brevifolia: Syah & Ghisalberti (1996): • Fruit contains germination inhibitory compound; catalpol and cyanogenic glycoside identified. Beattie (2009): • Leaf extract: piceine and a lignan glucoside (epipinoresinol-4-O-β-D-glucoside); the latter is also found in E. racemosa. Sweeney (2001): • Extracts have shown xanthine oxidase inhibitory activity, which may indicate usefulness in conditions such as gout. Everist (1981): • Contains small amounts of furanosesquiterpenes, apparently similar to those in Myoporum, detected in Queensland sample; no direct evidence of toxicity and not usually eaten in quantity by stock. Ghisalberti (1994a): • Sesquiterpene ketone (eremophilone) and analogues isolated. Barnes (2011): • Novel sesquiterpene lactones (mitchellenes A, B, C) and sesquiterpene acids (michellenes D and E) isolated.

318 Eremophila neglecta

Eremophila paisleyi

Eremophila sturtii (Turpentine Bush, Kerosene Bush)

MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary Ghisalberti (1994a); Richmond & Ghisalberti (1994): Ndi (2007b): Contains antimicrobial serrulatanes and the • Used in smoke treatment; leaf infusion to promote • naphthoquinone biflorin. general well-being. Anakok (2012): • Serrulatanes have shown anti-mycobacterial activity against Mycobacterium fortuitum and M. chelonae; also activity against gram-positive bacteria, but little activity against gram-negative bacteria. Latz (1996); Richmond & Ghisalberti (1994): Ghisalberti (1994a): • Leaves and twigs prepared as a decoction and used as • Sticky ornamental species. a wash for scabies. • Leaf resin contains sesquiterpene (spathulenol) and diterpenes. Maiden (1921c): Latz (1996): • Leaves: faint pleasant aroma when crushed • ‘Viscid exudation pervades all parts of • Fumes from smouldering branches used to relieve this plant: it often goes under the name of Turpentine Bush’. backache. • Shrub is reputed to have fly-repellent properties and Ghisalberti (1994b): branches were often used by early European settlers • Weed of pastoral areas. to thatch meat-houses. • Triterpene-based oil. Richmond & Ghisalberti (1994): Barr (1993): • Leaf infusion: sores, cuts, head colds, sore eyes; • Leaf essential oil: y-elemene (16%), antidiarrhoeal remedy. β-eudesmol (12%), aromadendrene (6%). • Branches (infusion) or twigs (burnt to ash): for Ndi (2007c): treating backache. • Contains antimicrobial serrulatanes, as well as Latz (1996): a naphthoquinone similar to biflorin. • Arrernte people believe that smoke produced from burning green branches dispels the clouds after excessive rains and floods. Johnston & Cleland (1943): • ‘Mr. Rheese informed us that the ash of “turpentine bush” was sometimes used for mixing with pituri’. Barr (1993): • Do NOT take internally • Leaf decoction as a wash on cuts, open sores (use as required). • Leaves: handful infused in bath daily for flu and colds. • Leaf decoction: boil leaves (handful boiled in a litre of water) and the face is held over vapour to relieve eye soreness. • Used in smoke to treat backache, bad cough, general sickness.

Many of the traditional medicinal uses of the Eremophila genus are suggestive of antibacterial activity, which has been supported by recent research. Early investigations determined that the leaf resin of Eremophila latrobei contained biflorin, a napthoquinone with antimicrobial activity (Ghisalberti 1994b). The fact that it is also present in Eremophila neglecta suggests that other species may contain this compound – which has recently been the subject of considerable research interest. Biflorin has shown antioxidant, immunostimulant and cytotoxic properties that suggest anti-tumour potential. In particular, it has demonstrated a strong inhibitory effect against various cancer cell lines (skin, breast and colon) – as well as anti-melanoma activity with

good cancer inhibitory effects and increased survival rates in animal studies (Vasconcellos 2011, 2007, 2005). Biflorin’s antioxidant and cellular protective properties were significant, demonstrating antigenotoxic and anti-mutagenic activity at low dose levels – interestingly, these effects were reversed at higher concentrations (Vasconcellos 2010, 2007).

Eremophila latrobei. (Courtesy Craig Nieminski, flickr)


Biflorin has been found in extracts of Clove (Syzygium aromaticum) (Oya 1997; Cai & Wu 1996) – and the fern Dryopteris crassirhizoma (Chang 2006). (Image courtesy Hafiz Issadeen, flick)

Sweetweed: A Traditional Herb with Potent Pharmacological Properties

Capraria biflora. (Courtesy Scott Zona CC-by-SA 2.0)

The genus Capraria is closely allied to Eremophila10 within the Scrophulariaceae family. The tropical American medicinal herb known as Sweetweed, Goatweed or Jamaican Tea – Capraria biflora (syn. C. lanceolata) – is of interest because it contains the antibiotic naphthoquinone biflorin, which is found in a 10 Australian species once classified as Capraria include Eremophila debilis (Capraria calycina) and Lindernia crustacea (syn. Capraria crustacea). The Lindernia genus contains around 45 native Australian species.

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number of Eremophila species. Recent studies have confirmed that Capraria biflora leaf extracts have analgesic, antimicrobial and antiinflammatory properties – while root extracts have antibacterial activity (Vasconcellos 2007; Acosta 2003). Sweetweed is traditionally used as a tonic in Belize, which has been a popular remedy for fatigue. The tea (a small handful of fresh leaves infused in 3 cups of water) was taken as an analgesic, anti-inflammatory and urinary tract tonic. It was also used to allay menstrual cramps in young girls, for rheumatic aches and pains, urinary tract (kidney and bladder) disorders, to ease cough, and as an anti-diabetic remedy. Investigations of a water extract of the dried leaves have shown hypoglycaemic properties in animals (Arvigo & Balick 1993). Other sources likewise mention the use of the leaves for pain relief, primarily in menstrual pain, postpartum (following childbirth), and for teething – as well as providing a remedy for otitis (ear infection), fevers (including influenza), and haemorrhoids (Lans 2007; Acosta 2003). In the Caribbean the herb has also been valued as a cleansing remedy and taken as a digestive aid – as well as for gastrointestinal tract dysfunction (diarrhoea, bowel inflammation). The bud tea was regarded as being useful for allaying biliousness. Occasionally the herb was recommended as a purge (taken with oil for an additional cleansing effect) and could be employed to regulate (start or stop) purge sessions when taken for 3 days with salt (Honychurch 1991). The use of the herb as an anti-inflammatory for skin disorders to relieve itching, particularly for scabies, has been mentioned. This could be linked to its essential oil component, which is sesquiterpene-based – with a high level of β-caryophyllene (29.6%) and y-muurolene (32.6%) (Fonseca 2006). The herb also contains sesquiterpenes (caprariolides) with insecticidal properties against a sweet potato crop pest (Cylas formicarius elegantulus) (Collins 2000). Furthermore, Sweetweed’s use as an eyewash may be linked to its antibacterial and anti-

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inflammatory activities. Indeed, there is an interesting patent for the use of Capraria biflora for treating senile cataract. Leaf extracts were shown to reduce or eliminate the characteristic lens opacity. Prolonged treatment had a rather dramatic preventive effect, even stopping a recurrence of the condition in those who had been previously affected – making it suitable for concurrent use in the surgical removal of cataracts (www.faqs.org/patents/ app/20090280204).

Berrigan (Eremophila longifolia) is widespread throughout continental Australia, although it does not favour wetter regions along the eastern coastline. It can produce flowers of variable colour (red, pink, orange or yellow) and is a good honey resource. This resilient shrub is tolerant of a wide range of soils and environments, surviving drought, unpredictable weather changes, variable rainfall and fire. The plant’s root system is excellent for preventing soil erosion, it provides a very good windbreak, and is an important refuge and food resource for wildlife. Berrigan is considered the best Eremophila for use as a fodder resource and is an important ritual and medicinal plant for Aboriginal people throughout its range. (Image courtesy Melburnian)

Eremophila longifolia: A Variable Essential Oil Eremophila longifolia essential oil illustrates the significant chemical variability that is possible within a single species. Originally, an essential oil rich in safrole and methyleugenol was distilled (Della & Jefferies 1961) that raised concerns regarding the medicinal use of the plant: ‘Since safrole has been

shown to be quite toxic, the drinking of a tea made from the plant may be hazardous and ought to be discouraged’ (Lassak & McCarthy 1992). However, later studies found that a lot of variation could occur. One collection from the Northern Territory even yielded a negligible amount of essential oil, which contained ɑ-pinene (Ghisalberti 1994a; Barr 1993). Recent essential oil analysis of samples from the arid regions of New South Wales noted: ‘it was also observed that none of the species encountered in the field during collection were found to produce the characteristic aniseed or nutmeg like odours which may be associated with the presence of safrole or other phenylpropanoids’ (Smith 2010). Three oil chemotypes have been established (Smith 2010): Isomenthone-based oil (61–87%): fairly high • yield (3–6%) and a pleasant ethereal peppermint fragrance that was enhanced by menthone (1– 22%) and other p-menthane terpenoids in the oil. Other components of interest include ɑ-terpineol (8–11%) and piperitone (0.5–4%). Isomenthone and menthone have antimicrobial potential, as well as acaricidal activity. These compounds are also present in a number of medicinal herbs that have been utilised as a vermifuge. Karahanaenone-rich oil (81–82%): lower yield • (0.5–2%) and contained similar minor constituents to the isomenthone-based oil – e.g. ɑ-terpineol (4–11%), limonene (1–2%). Karahanaenone is a relatively uncommon compound that has been found in oil of Hops (Humulus lupulus), Tanacetum ligulatum, Nigella sativa (seed) and species of Cupressus (leaves). Derivatives of this compound are utilised in the flavour and fragrance industry. Borneol-based oil: low yield (0.4%). Main • components were borneol (32%), fenchol (20%) and bornyl acetate (7%). Limonene levels could be quite high (10%). Other terpenes of interest included sabinene (5%), terpinolene (5%) and 4-terpineol (4%). This oil form showed some chemical similarities with a previous sample from the Northern Territory, albeit the latter was characterised by ɑ-pinene (55%) as the major component. Borneol, which is in found in numerous medicinal herbs, has anti-inflammatory, analgesic and sedative potential (Dai 2009).


It is worth noting that essential oil constituents such as monoterpenes have shown skin-penetrating properties. This can enhance the bioavailability of other chemicals and promote their ability to permeate the skin. This quality may well have played a role in the efficacy of Aboriginal medicinal preparations such as ointments, smoking or inhalation therapies. Some chemical forms of the plant would probably have been considered more useful therapeutically, which could have influenced the selection of traditional harvesting sites. Chemical variation may not be uncommon in the Eremophila genus. Certainly it occurs in different varieties of the Turpentine Bush (Eremophila fraseri), and chemovarieties significantly influence the toxicity of Myoporum deserti (Smith 2010; Ghisalberti 1994a). This would suggest that there is a lot more to be discovered before the chemical puzzles of the genus Eremophila are unravelled with any certainty.

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2007c), E. gibbosa (Ndi 2007a) and E. neglecta (Anakok 2012; Ndi 2007b). • Eremophila duttonii demonstrated the highest potency of all the species studied. Extracts were particularly active against gram-positive organisms, notably Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae – as well as Enterococcus faecalis. Importantly, extracts exhibited activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) (Smith 2007; Tomlinson & Palombo 2005; Palombo & Semple 2002, 2001). Alcoholic extracts were also active against the food-borne pathogens Listeria monocytogenes and Clostridium perfringens (Shah 2004).

A Focus on Antimicrobials

The Harlequin Fuchsia Bush or Budda (Eremophila duttonii) is a fairly widespread species of inland Australia that was first described by Ferdinand von Mueller in 1859. (Image courtesy Arthur Chapman, flickr)

In the last decade numerous reports have surfaced regarding strong antimicrobial potential for the Eremophila genus, although these plants do not appear to be particularly active against gram-negative bacteria (e.g. Pseudomonas aeruginosa, Escherichia coli): • Antibacterial studies: Eremophila linearis and E. granitica (Croft 1981), E. duttonii (Tippett & Massey-Westropp 1993), E. sturtii (Liu 2006, Ndi

Antibiotic-resistant bacteria such as MRSA (pictured here) and VRE developed within a decade of the relevant antibiotics coming into general medical practice. Resistance developed because some bacteria are able to produce the enzyme penicillinase (β-lactamase), which can break down penicillin, thereby rendering the drug useless. Destroying all the antibiotic-sensitive bacteria during treatment may well leave only a few resistant cells alive – yet these strains are perfectly able to reproduce in the hundreds of thousands. This can allow the highly resilient strain to propagate with very little other microbial competition. β-lactamase inhibitors (e.g. clavulanic acid from species of Streptomyces) have been appended to various antibiotics to increase their efficacy, although there are many bacteria that are not sensitive to these drugs (Sternbach & Varon 1992). (Image courtesy Jeff Hageman, CDC)

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Scabies Infections

Typical pattern of scabies mite burrowing in the skin. The parasite’s entry point is found at the scaly-skin site, which shows tissue damage due to scratching. The mite is a dark spot at the end of the burrow on the top right. In the tropics scabies infections can be particularly difficult to diagnose. Despite intense itching, there may be no sign of the mite under the skin – and the symptoms can mimic a range of other skin diseases such as eczema, impetigo, dermatitis herpetiformis, furunculosis, papular urticaria, diverse allergic reactions, eczema herpeticum and other viral exanthemas. It can also resemble syphilis infection – or irritation due to parasitic mites and insects (chiggers, lice, fleas, bedbugs) (Walton 2004). (Image courtesy Michael Geary, Wikimedia Commons, Public Domain)

Australian Aboriginal communities suffer from an extremely high incidence of scabies infection and its distressing complications – perhaps the highest in the world (Walton 2004). Scabies is one of the three most common skin disorders – tinea (fungal infections such as ringworm) and pyoderma (a general term for infected skin problems) are the other two. Importantly, scabies can become complicated by serious secondary infections due to Staphylococcus aureus and grampositive streptococci11 that can result in bloodborne infections and rheumatic fever. 11 Staphylococcus aureus and S. epidermis are commonly implicated in dermal (skin) infections, while Streptococcus pyogenes can be associated with the development of impetigo. Staphylococcus aureus, Streptococcus pneumoniae and S. pyogenes are involved in ENT (ear, nose and throat) infections such as tonsillitis, pharyngitis and otitis. Conjunctivitis has been associated with Staphylococcus aureus, S. epidermis and species of Propionibacterium, as well as streptococci and corynebacteria (Smith 2007; Palombo & Semple 2001).

In Aboriginal communities a remarkably high level (50–70%) of Streptococcus (group A) skin infections are probably associated with underlying scabies infection. This is extremely important because this is a risk factor that has been linked to the subsequent development of renal disease. The incidence of end-stage renal failure, which is 21 times higher than that of the general population, is reflected in a high rate of childhood glomerulonephritis (a serious form of kidney disease) following streptococcal infections. The incidence of rheumatic fever resulting in rheumatic heart disease is equally high (Walton 2004). Immune system function is of pivotal importance in susceptibility to scabies. Initially, there is an increase in mite numbers that triggers the immune system, which acts to limit the level of infection. While the allergic reaction proceeds more quickly (within 24 hours) if reinfection occurs, in around 60 per cent of cases the infection is unsuccessful due to an effective immune response. However, severe infections occur when the normal inflammatory reaction in the initial skin lesion is compromised, and there is subsequent failure of host immunity. The situation can be compounded by the fact that the parasite itself appears to secrete antigens that inhibit the natural inflammatory and immune responses. If this results in uncontrolled parasite infiltration and systemic reactions, the immune system becomes even further compromised. In severe instances a disfiguring non-healing ‘crusting’ skin reaction can develop (albeit uncommon) that is associated with an extremely high parasite burden (over a million have been detected in very severe cases) (Walton 2010). It is unsurprising, therefore, to find that individuals with immune system dysfunction are more likely to suffer serious infection – notably the elderly, and those with chronic fatigue, AIDS, cancer or drug exposure. The latter includes conventional drugs that act as immunosuppressants, notably steroids and chemotherapy. Situations where there is overcrowding, inadequate hygiene, poor


nutritional habits and other dietary indiscretions will only compound the problem (Walton 2010). In addition, even when treatment is successful, the rash and itching can continue for several weeks – probably due to dead mites or mite products causing an allergic response. In immune-suppressed individuals, a nodular type of lesion can develop that persists for several months after treatment – which, once again, complicates the clinical picture and evaluation of treatment efficacy. Historically, crusted scabies has been

Numerous species of Eremophila have been utilised for the treatment of scabies (Sarcoptes scabiei) infections. Unfortunately, there does not appear to have been serious investigation into the efficacy of the remedy. The species utilised include the Emu-bush or Rock Fuchsia (Eremophila freelingii) – an important resin-containing medicinal plant of Central Australia. This shrub is found over a wide area of the Northern Territory and South Australia, extending to western Victoria and New South Wales. It is also found in Western Australia. The herb, which is highly aromatic, has also been a popular remedy for influenza and chest colds. (Images courtesy Roger Fryer and Jill Newland)

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associated with leprosy patients. There appears to be an intriguing link between these conditions. The immune defects that predispose some people to develop leprosy may also be present in those who suffer severe scabies infections – although currently there is no way of establishing susceptibility and treatment options are limited. The clinical picture of psoriasis is also somewhat similar to that of crusted scabies (Walton 2010). Other Eremophila species may have interesting antibacterial potential and reviews of the genus continue to be undertaken. The main antibacterial components are diterpenoids12 (Smith 2007; Liu 2006). Resinous exudates contain a great diversity of diterpenes, with the main resin-yielding species being: Eremophila abietina, E. fraseri, E. flaccida, E. ramiflora and E. viscida. The amount of resin present in these shrubs, as well as its consistency, and distribution in the plant, can vary significantly. The average yield is around 5–10 per cent – although levels as high as 20 per cent have been noted in some dried plant specimens. Sometimes the resin, which dries into a transparent varnish, is so abundant that it can be simply chipped off the plant (Richmond & Ghisalberti 1994).

The Spotted Poverty Bush (Eremophila abietina) is an extremely pretty Western Australian species that was first described in 1925. It has a limited inland distribution northeast of Kalgoorlie. The species name abietina refers to the fir-like foliage of the plant. (Image courtesy Melburnian) 12 A furanosesquiterpene with mild antibacterial activity has also been identified.

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The unique character of Eremophila-derived diterpenes and sesquiterpenes inspired a review of 72 native resin-yielding species, of which 33 demonstrated antimicrobial properties. Eremophila virens was of particular interest, with an inhibitory action on MRSA. Other species with antibacterial properties worthy of further investigation include E. drummondii, E. linearis, E. serrulata and E. acrida – as well as an undescribed species that was botanically affiliated to E. prolata (Ndi 2007a, 2007b). In the process, a number of other native plants with equally interesting antimicrobial potential were identified. Extracts from Acacia kempeana (leaves) and Lepidosperma viscidum (stem base) were active against VRE (vancomycin-resistant enterococci). Eremophila

Eremophila drummondii (Drummond’s Poverty Bush). This species is widely distributed inland in southern Western Australia. Chemically it contains two aromatic sesquiterpenes (that are related to phytoalexins found in some Ulmus species) with potential to act as precursors for the male anti-fertility agent gossypol (Richmond & Ghisalberti 1994). Gossypol, which is naturally found in cottonseed oil, was linked to a low level of male fertility rates in China. Investigations of its practical value in drug development were, however, later discontinued due to toxic side-effects. (Image courtesy Peter Matthews, flickr)

alternifolia (leaf ) was active against MRSA, as was the mistletoe Amyema quandang (leaf extracts) (Palombo & Semple 2002, 2001). Investigations have also determined that methanol extracts of Eremophila maculata (leaves), Acacia auriculiformis and Acacia bivenosa (phyllodes) possess antibiotic effects (Pennacchio 2005). Antimycobacterial studies of other native species indicated that extracts of Eremophila alternifolia (leaf and stem) and E. longifolia (leaf ) were active against Mycobacterium fortuitum and M. smegmatis. Activity against the latter was also demonstrated by Acacia ligulata (bark, leaves) and Pterocaulon sphacelatum (aerial parts). These herbs have been traditionally utilised similarly to Eremophila for treating colds, respiratory disorders and skin sores. Pterocaulon has also been recommended for eye complaints (Meilak & Palombo 2008). In addition, serrulatane compounds have been isolated as active antimycobacterial components of Eremophila neglecta (see Table 7.2; Anakok 2012).

Eremophila alternifolia is found throughout much of the southern half of the continent: Western Australia, South Australia and central Australia, ranging to western New South Wales, parts of Victoria and Tasmania. (Image courtesy Melburnian)


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Verbascoside: A Versatile Pharmacological Agent

Somewhat more unexpected is the potential of the Native Fuchsia as a cardioactive agent. Eremophila alternifolia (leaf extract) has shown cardiotonic activity in animal studies, with a lowering effect on systolic (but not diastolic) blood pressure13 (Pennacchio 2005). Another species with cardioactive properties is Eremophila longifolia. The active components were identified as verbascoside and geniposidic acid (an iridoid glucoside) – with the latter compound being uncommon in the genus (Pennachio 1996, 1995). Interestingly, this species also contains pinoresinol (a lignan that is characteristic of Pine resins), derivatives of which have recognised cardiotonic properties14 (Syah & Ghisalbert 1996).

Eremophila bignoniiflora is a widespread species throughout much of Queensland, New South Wales and central Australia, ranging to northern Western Australia. (Courtesy Ethel Aardvark, Wikipedia)

13 Blood pressure is measured as a maximum (systolic) and minimum (diastolic), expressed as a measurement (mmHg) systolic/diastolic. The most desirable range is 90–119/60–79 – although in adults it can average 140/90, albeit this is considered to be a little high. Cardiovascular disease risk increases with higher measurements, which indicate compromised vascular function. 14 Epipinoresinol is an important component of the medicinal herb Eucommia ulmoides, which has a substantial reputation as an effective antihypertensive remedy (Greenway 2011; Luo 2010; Sih 1976). In addition, pinoresinol from Sambucus williamsii has demonstrated antifungal properties of clinical interest (Hwang 2010).

Fruit of Eremophila bignoniiflora. (Courtesy Olga Blokhman, TopTropical.com)

Verbascoside appears to be fairly widespread in the Eremophila genus. Its presence has also been confirmed in extracts of Eremophila bignoniiflora and E. cuneifolia. This compound has extremely interesting pharmacological potential: antihypertensive, anti-thrombotic, wound-healing, antitumour and analgesic properties, as well as having an anti-tremor effect (via potentiation of the activity of L-dopa15) (Funes 2010; Herbert 1991; Dell 1989). In addition, verbascoside has antibacterial and antiinflammatory activity which has suggested potential for use in intestinal inflammatory conditions such as colitis and periodontal inflammation (periodontitis) (Paola 2011; Esposito 2010a; Speranza 2010, 2009; Mazzon 2009; Sheng 2002; Avila 1999; Pardo 1993). Verbascoside has also been proposed as a useful antioxidant, anti-inflammatory, photo-protective and skin-healing ingredient for cosmetic purposes – leading to investigations of its stability and solubility for commercial use (Vertuani 2011; Sinico 2008). Interestingly, a patent has been filed with regard to a combination of verbascoside and luteolin for treating pigmentation disorders, notably as a skin-whitening cosmetic16 (Sene nd).

15 L-dopa, which is formed from an amino acid (L-tyrosine), is an important precursor for a number of extremely important catecholamine neurotransmitters (dopamine, noradrenaline, adrenaline). L-dopa is utilised for treating a number of disorders characterised by tremors, such as Parkinson’s disease. 16 There is also a Japanese patent for the use of the eremophilane cacalol, or plant extracts from the Asteraceae genus Cacalia, as a skin-beautifying and skin-whitening agent (Kitagawa & Kitagawa 2010, Japanese Patent JP201004304).

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Furthermore, experimentally, verbascoside has shown a remarkable diversity of treatment potential: • healing traumatic spinal cord injury (Genovese 2010) • for treating nerve pain (Isacchi 2011) • as an antioxidant antitumour agent (Zhang 2002) • for the prevention of muscular fatigue during exercise (Zhu 2010; Liu 2003; Li 1999; Liao 1999) • anti-Herpes virus activity (Martins 2009) • as a gastroprotective agent (Singh 2010) • and, possibly, a protective effect on neurodegenerative disorders, including drug-induced brain damage (Esposito 2010b; Qiusheng 2005; Sheng 2002).

Olive grove near Toowoomba, Queensland. Olives are a rich phenolic resource. During processing for olive oil a large proportion of the phenolic components are lost in the wastewater, including verbascoside. The recovery of this compound and related phenolics (isoverbascoside etc.) from olive oil processing waste is therefore an interesting proposition with good commercial prospects. This resource could well provide antioxidants useful for food-processing purposes (Cardinali 2012, 2011). Studies have established excellent antibacterial properties of an olive-waste phenolic extract (Tafesh 2011; Lee & Lee 2010). Australian investigations of olive mill waste have also established antioxidant, antimicrobial and molluscicidal for these phenolic-based extracts (Obied 2007). (Image courtesy Karsten Wendland, Wendland Olives)

(Right) Buddleja globosa has been utilised in Chile as a wound-healing herb. Methanol extracts of the plant, which showed substantial anti-inflammatory and analgesic properties, contained luteolin-7-O-glucoside and verbascoside as the primary active components – with the latter showing significant antinociceptive activity (Backhouse 2008a, 2008b).

Butterfly Bush (Buddleja davidii), which is naturalised in Australia, is a verbascoside-rich shrub, with cell cultures containing around 80 per cent of this compound. Extracts also contain isoverbascoside, leucosceptoside A and martynoside (Vertuani 2011). The plant, which is of Chinese origins, has been utilised as a diuretic and antiseptic agent, and is particularly suited for the treatment of urogenital problems. Butterfly Bushes have been valued as vulnerary, sedative, analgesic and anti-inflammatory agents – and were popularly utilised for wound healing and respiratory tract disorders (coughs, colds and catarrh) (Houghton 1984). In many countries Buddleja davidii has escaped from cultivation to become an undesirable weed due to its invasive habit and ability to readily colonise wastelands.


Australian Myoporaceae: Intriguing Chemical Complexity An enormous amount of work has been done on the chemistry of the Australian Myoporaceae (genera: Eremophila and Myoporum) which has resulted in numerous discoveries, and a rather detailed analysis of some species. Myoporum species tend to be characterised by furanoid sesquiterpenes in their essential oil. Associate Professor Emilio Ghisalberti commented: ‘The furanosesquiterpene compounds from the Myoporaceae and other

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geographically widespread genera (Athanasia, Eumorphia, Gymnopentzia) have been studied extensively because of their toxicity to stock through liver damage and also because they are probably precursors of a group of … furans with potent lung toxicity. It seems reasonable to assume that any species of the Myoporaceae that is known to contain one or more of these compounds must be regarded as potentially toxic to higher animals.’ Eremophila species differ in that they can contain novel diterpenes, some of which are unique. Table 7.2 outlines these chemical discoveries.

Table 7.2 Brief Summary of the Major Chemical Components in the Myoporaceae This table is based on The Phytochemistry of the Myoporaceae (1994b) by Professor Emilio Ghisalberti, Department of Chemistry, University of Western Australia. Later additional references are cited in the table individually. Chemical classification Alkaloids

Monoterpenes These essential oil compounds are usually volatile in nature. Therefore their presence in essential oils can be difficult to quantify and they can be easily overlooked in chemical investigations that focus on isolating major chemical components from extracts. Sesquiterpenes (2 different groups) Furanosesquiterpenes have rated particular interest due to their potential toxicity. Carbocyclic sesquiterpenes have been of interest as a source of aromatic compounds

Main compounds of chemical interest (species) Alkaloids: most have not been characterised, although some species can contain reasonable amounts.

Details and notes The following have shown positive tests for alkaloids: • Eremophila fraseri (strong positive). • Species with a moderately positive reaction include: E. alternifolia, E. cuneifolia, E. drummondii, E. duttonii var. parvifolia, E. foliosissima, E. latrobei, E. leucophylla, E. longifolia, E. maculata, E. margarethae, E. oldfieldii, Myoporum acuminatum, M. insulare. Iridoid monoterpenes: • Geranyl acetate (Eremophila abietina). • Myoporum deserti has a number of • 1,8-cineole (E. scoparia, E. dalyana). chemical varieties that influence its • Verbenone (E. dempsteri). toxicity. • Fenchone (E. caerulea, E. alternifolia). • M. deserti is considered toxic to stock, • Limonene (E. alternifolia). although some chemovarieties are not. • Camphorene (E. cuneifolia) . • One variety is also immune to attack • Pinene (small amounts in essential oils: E. from grasshoppers. duttonii, E. freelingii, E. longifolia). Note: Ants (Iridomyrmex) also contain • Iridoid monoterpenes (Myoporum deserti). iridoids in their defence secretions. • Iridoid glycosides (M. insulare) Camphorene: also found in the essential oil • Geniposidic acid (monoterpene glycoside: E. of Hops. cuneifolia). Furanosesquiterpenes: oxygenated farnesols Furanosesquiterpenes: in essential oils – i.e. ngaione and derivatives These toxic sesquiterpenes have attracted (Myoporum laetum, M. acuminatum, M. deserti, a lot of interest, notably ngaione. This was Eremophila latrobei). first isolated in 1925 from New Zealand • Freelingyne and analogues (E. freelingii). species M. laetum, and later found in the • Dendrolasin (M. rotundifolia). Australian species M. deserti – although not all chemical variations (chemovarieties) of Carbocyclic sesquiterpenes (classes: bisabolene, the latter species contain it. eudesmane, eremophilane, aromadendrene, • Ngaione and related furanosesquiterpenes cadinane, zizaene). are stock toxins, with a notable • Anymol (M. crassifolium essential oil). hepatotoxic effect. • Eremophilone (E. mitchellii wood oil). • Ngaione is chemically similar to • Eudesmol and derivatives (E. scoparia). ipomearone, a toxic phytoalexin • Calamenene and hydroxycalamenene (aromatic produced as a defensive chemical by components of essential oil of E. drummondii Sweet Potatoes (Ipomoea batatas) that and E. virens). undergo insect or fungal damage.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary • Oplopanone (E. miniata; related compounds found in the Japanese shrub Oplopanax japonicus). • Spathulenol (E. cuneifolia). • Elemol (E. dalyana, E. flaccida, E. leucophylla). • Cadinene sesquiterpenes (resin from E. virgata and E. interstans). • Zizaene type sesquiterpenes (E. georgei, E. metallicorum, E. subteretifolia; also found in species of Vetiver grass).

• N gaione is related to furfural, a compound with fungicidal and bactericidal properties that has been used to treat fungal infections such as athlete’s foot and swimmer’s itch (Brooker 1993). • The toxicity of other sesquiterpenes in various species (e.g. in M. acuminatum, M. deserti) can vary. These compounds include myodesmone, isomyodesmone (and other derivatives) and the precursor myoporone, as well as dehydromyoporone. • Epingaione (and analogues: dehydrongaione etc.) is the toxic compound in M. deserti • Dendrolasin is of interest because it has been found in the ant Dendrolasius fuliginosus; the wood oil of Torreya nucifera; and in a marine sponge (Oligoceros haemorrhages). • Ketones present in M. deserti have also been found in Athanasia crithmifolia (a herb of the Daisy family, Asteraceae).

Diterpenes Desert-adapted Eremophila species can have a substantial resin coating on their leaves and terminal branches (up to 20% dry weight) which is largely composed of diterpenes. Research has shown diterpenes may have substantial medicinal potential.

Resins of Eremophila spp. are generally composed of mixtures of diterpenes and flavones (although in a few species resin may be sesquiterpene-based). There are a number of distinct classes of diterpenes: • Acyclic diterpenes (e.g. E. glutinosa and E. linearis). • Cembranes, e.g. epoxycembranediol (resin of E. georgei, E. abietina, E. clarkei, E. dempsteri, E. granitica, E. fraseri, E. platycalyx, E. metallicorum). Eremolactone (E. fraseri and E. freelingii) was the first isolated. • Bisabolene isoprenologues (E. foliosissima and E. gilesii). • Cycyloserrulatanes (E. serrulata) and geranylgeraniol derivatives (E. exilifolia, E. glutinosa, E. petrophila). • Viscidanes (E. viscida). • Serrulatanes have been found in a large number of species, e.g. dehydroxyserrulatic acid (E. serrulata), biflorin (E. latrobei). • Decipianes are closely related chemically to serrulatanes (E. decipiens, E. clarkei, E. georgei). • Cedrane isoprenologues (E. georgei and E. gilesii). • Eremanes (varieties of E. cuneifolia, E. fraseri, E. freelingii, E. georgei, E. gilesii etc.).

Other compounds Sterols, triterpenes Fatty acids Flavonoids Lignans Alkaloids

Sterols and triterpenes have not been found in any significant amounts in the Myoporaceae. • Sterols or triterpenes are present in E. mitchellii (leaf extracts), E. longifolia and Myoporum deserti. Fatty acids: • no systemic study has been undertaken of the family, although resins tend to contain significant amounts of fatty materials (palmitic, steric, oleic, linoleic acids). • Palmitoleic acid (E. abietina). • Palmitic acid (M. deserti). Flavonoids: • occur widely in Eremophila and Myoporum: flavanone, dihydroflavonol, dihydroflavanol acetate (the latter may possess intense sweetening properties) • Flavonoids are found in a significant portion of Eremophila resins. • Flavones (Myoporum tenuifolium).

Geranylgeraniol derivatives are rare as significant components of plants, they are more commonly found in algal species. Cembranes are found in oleoresins (e.g. conifers), tobacco leaf, Anisomeles genus (Lamiaceae family); termites produce cembranes, as do some marine invertebrates (the Coelenterate phylum ) Serrulatanes: • Cycloserrulatane (E. serrulata) is the original source of the serrulatanes. • Biflorin has antimicrobial properties • Serrulatanes are of interest as they have been found in Marine Sea Whips (Pseudopterogorgia spp.) that have shown potent analgesic and antiinflammatory potential. • Seco-pseudopterosins (marine-derived isoprenologues) that are structurally related to serrulatanes have shown potent anti-mycobacterial activity (Smith 2007). Cedrane isoprenologues: the sesquiterpene counterpart is α-cedrene, which has been found in the genus Cedrus, as well as in lac resin. Eremanes: eremolactone (E. fraseri resin and E. freelingii essential oil). A number of other components have been discussed in the text: • Aromatics: safrole and methyl eugenol. It should be noted that these compounds have anaesthetic and bactericidal properties, with methyl eugenol also possessing sedative and fungistatic activity. • Mannitol (principal component of resin of Myoporum ‘manna trees’). • Verbascoside (a caffeoyl ester disaccharide) • Cyanogenetic compound: prunasin.


Eremophila decipiens is one of the resin-yielding species that contains diterpenes (decipianes). (Courtesy Melburnian)

Eremophilanes from the Asteraceae

Cacalia delphinifolia. The genus Cacalia is composed of around 80 species (a number have now been reclassified in the genera Arnoglossum or Adenostyles) – of which 50 are found in China, with the remainder in America. It has been suggested that around half of the Chinese species have been utilised as remedies for cough and phlegm, and were valued for ‘invigorating the blood’ (improving the circulation) (Wang 2003). (Image courtesy Allison Carson, flickr)

A couple of genera in the Asteraceae family contain medicinal plants that are of chemical interest due to their links with eremophilane sesquiterpenes17 – notably the closely related genera Cacalia and Psacalium. Sesquiterpenes of 17 See Zhang 2010 for a chemical review of these compounds.

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this type are present in root extracts of Cacalia ainsliaeflora and C. pilgeriana (Mao 2003) – as well as the medicinal herb C. delphinifolia. Eremophilanes have shown interesting pharmacological properties that suggest links with the medicinal use of these herbs. Indeed, the Asian edible wild herb Cacalia delphinifolia (also C. delphiniifolia), which contains the eremophilane cacalol, has been utilised as an anti-cancer remedy. This compound has experimental chemopreventive activity (apoptosis-inducing) and a synergistic effect with the anticancer drug Taxol – which suggests therapeutic potential for the treatment of breast cancer. Other components with anti-tumour activity are also present in the herb (Liu 2011; Nishikawa 2008). Interestingly, cacalol has shown significant antioxidant properties, as well as potent neuroprotective activity (Shindo 2004). A few traditional Mexican medicinal Psacalium species also contain eremophilanes, including cacalol and its derivatives. This genus ranges from the southern United States to Guatemala. Six species in a classification that are known as ‘Matarique’ herbs have been utilised for treating diabetes, renal and liver disorders (Arciniegas 2009; Campos 2009). The antihyperglycaemic and antimicrobial properties of cacalol tend to support the traditional use of Cacalia decomposita (syn. Psacalium decompositum) as an antidiabetic remedy (Shin 2004; Hernandez-Galicia 2002; Inman 1998a). Indeed, hypoglycaemic furanoeremophilane and eremophilanolide sesquiterpenes (epicacalone, cacalone, cacalol, dimaturin) are the subject of a patent for their use in the treatment of diabetes (Inman 1998b). However, it would appear that other active compounds are present. Psacalium compositum, which had hypoglycaemic effects in animal studies, contains hypoglycaemic fructooligosaccharides (Jimenez-Estrada 2011). In addition, good anti-inflammatory activity has been demonstrated for P. sinuatum root extracts that contained eremophilane derivatives18 (Arciniegas 2009). As well, cacalol has been identified as a major antimicrobial component of

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Psacalium radulifolium (root extract) (GarduñoRamírez 2001). Investigations of an essential oil of the flowers and leaves of Seneci aegyptius var. discoideus demonstrated substantial antifungal activity against Candida albicans and moderate antibacterial activity (grampositive bacteria). The primary component of the oil was identified as an eremophilane, while samples of root-extracted oil contained furanoeremophilanes. One major oil component (1,10-epoxyfuranoeremophilane) demonstrated significant activity against gram-negative bacteria (El-Shazly 2002). Later studies have confirmed antifungal properties of extracts (aerial parts) as well as antibacterial activity against Klebsiella pneumoniae, antiinflammatory activity and anticancer potential – with the latter being strongly associated with the flavonoid rutin (Hassan 2012).

Senecio nemorensis. In the last decade, researchers from across the world have isolated eremophilanes from various Senecio species – S. aegyptius var. discoideus (Egypt), S. asirensis (Saudi Arabia), S. mairetianus (Mexico), S. miser (Spain), S. nemorensis (China), S. santelisis (Argentina), S. sinuatus (Mexico), S. toluccanus (Mexico) and S. tsoongianus (China). (Image courtesy Cwmhiraeth, Wikimedia Commons, CCby-SA 3.0 Unported)

18 While they include cacalol, more active candidates were identified – i.e. calcalone and epi-cacalone. A number of other, less active, anti-inflammatory components are also present in the genus (e.g. cacalohastin and radulifolin) (Arciniegas 2009).

Creeping Bentgrass, Agrostis stolonifera. Some eremophilanes have been of interest as phytotoxic agents. One study has shown that they could substantially inhibit the growth of Bentgrass (Agrostis stolonifera) (Cantrell 2007). This resilient grass is valued for regeneration works as it will colonise wetlands, woodlands, coastal and disturbed habitats – and has some fame as a turf plant, particularly for golf courses. In addition, the grass remains green during dry spells and can be used as a fodder for livestock. (Image courtesy Alfred, Wikipedia, CC-by-SA 3.0 Unported)

Dodonaea: A Rather Remarkable Continental Pioneer

Dodonaea viscosa, purple fruiting form. (Courtesy Kim & Forest Starr, Hawaii)


Dodonaea boroniifolia (above) is widespread throughout the eastern states from Victoria to Cape York, while D. falcata (below) has a more restricted distribution in New South Wales. (Images courtesy Brian Walters)

The purple fruiting form of the Hop-bush, Dodonaea viscosa, is often favoured as a garden ornamental. Hopbush fruits have been utilised for beer-brewing purposes. (Image courtesy Kim & Forest Starr, Hawaii)

Dodonaea in Australia

The Thread-leaf Hop-bush (Dodonaea filifolia) is a Queensland and New South Wales species. (Courtesy John Elliott, SGAP Townsville)

In Australia there are 70 Dodonaea species –with nine subspecies and seven varieties. Because the older literature did not have this degree of differentiation there can be a fair amount of confusion with regard to subspecies and/or varieties. Dodonaea viscosa is the most prolific and is found throughout the continent. Ultimately seven subspecies were established: angustifolia, angustissima, burmanniana, cuneata, mucronata, spatulata and viscosa – a few of which were once thought to be individual species. In addition, a couple of species were formerly considered to be varieties: Dodonaea polyandra (D. viscosa var. vulgaris or var. laurina) and D. megazyga (D. viscosa var. megazyga).

Dodonaea viscosa subsp. burmanniana. (Courtesy John Elliott, SGAP Townsville)

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Common Hop-bush o r Large-leaf Hopbush (Dodonaea triquetra) is primarily found along the east coast of Australia, ranging from Victoria to northern Queensland. (Image on left courtesy Peter Woodard)

to the true hops, but are not botanically related to them. The resemblance was sufficient for beer-thirsty pioneers to use them as a substitute in brewing and, as it turned out, they were an adequate replacement, imparting a satisfactorily bitter flavour to the brew’. Dodonaea angustissima (D. viscosa subsp. angustissima), the Slender Hop-bush, was among the more favoured species utilised for this purpose. Interestingly, these shrubs belong to the Sapindaceae family, which is well known for containing saponins with foaming soap-like qualities. Indeed, the Foambark Tree (Jagera pseudorhus) is a native rainforest Sapindaceous species that was once used as a foaming agent for beer.19

(Left) Hops on the vine.

(Below) Aboriginal group working in a hop-bush garden, 1882. (Part of collection ‘Album of views of Tasmania, Victoria and South Australia, from the private library of Harry GrattanGuinness’. Published in: Fine Art Photographs of Victoria by Fred Kruger). (nla.picvn3082703-v)

Brilliant Hop-bush (Dodonaea microzyga) is widespread in central Australia, mainly in South Australia and Western Australia (southern half of the state), and ranging to outback New South Wales. (Images above courtesy Melburnian)

The Hop-bush (Dodonaea viscosa) is a native shrub that gained its name from the fruits being utilised by early settlers as a beer-brewing alternative to Hops (Humulus lupulus), as noted by Alan and Joan Cribb (1981): ‘These fruits show a superficial resemblance 19 See Volume 3 for further details on the Sapindaceae.

Hops (female flower clusters) have provided a bittering agent for brewing enterprises over many centuries, with their recorded use dating back to the eleventh century. Hops benefit the brewing process by adding flavour and aromatic qualities, and counterbalancing the sweetness of the malt. They also make an antimicrobial contribution to the brew, favouring the activity of brewer’s yeast over less desirable


microorganisms such as Lactobacillus. Certainly, long ago, beers made with Hops were noticed to be less prone to spoilage, which encouraged their use over other natural bitters such as Dandelion, Burdock, Heather, Mugwort etc. This is possibly linked to Hops components such as transhumulone and colupulone (Priest & Campbell 2003).

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The Hop-bush, notably Dodonaea viscosa, has an international reputation as a febrifuge, antiinflammatory and analgesic remedy. It also has soothing anti-pruritic properties, antibacterial, antifungal and wound-healing activities. This herb has been utilised in healing systems across the world (see Table 7.3), with numerous traditional uses attesting to its efficacy.

Hop-bush seeds have demonstrated experimental effects on the central nervous system that suggest good anticonvulsant and analgesic potential (Krupanidhi 2007). The fact that Dodonaea viscosa leaves were chewed in Peru as a stimulant tends to suggest that the shrub itself may likewise possess valid effects on the nervous system (Cribb & Crib 1981). (Image courtesy Kim & Forest Starr)

Hop-bush: split dried fruit, with seed within the winged capsule.

Dodonaea viscosa showing red and green fruiting patterns and male flowers. Most species of Dodonaea have male and female flowers on different plants (although there are bisexual flowers) and a short flowering period. The flowers are quite inconspicuous, which allows for easy winddistribution of the pollen. The most distinctive aspect of the genus is the colourful winged fruits. (Images courtesy Kim & Forest Starr, Hawaii)

Dodonaea viscosa subsp. angustifolia (D. angustifolia) and D. viscosa have interchangeable uses as medicinal plants. Both species are known by the name ‘Sand Olive’ in the tropical and subtropical regions of Africa – where they can have a reputation as problematic weedy trees. (Image courtesy JMK, Wikimedia Commons, CC-by-SA 3.0 Unported)

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Table 7.3 Medicinal Use of the Dodonaea Genus: Antimicrobial and Healing Properties Traditional uses and investigations (details) Traditional use D. viscosa: Skin problems: widely used for treating wounds, skin irritation, rashes, itching conditions, ulcers etc (India, Pakistan, Philippines, Hawaii, New Caledonia, Burma, Africa, Australia, Mexico) (Riley 1994; Ghisalberti 1986). • Numerous authors mention use of the infusion or decoction of leaves for treating skin disorders. Bark also used for preparing washes and in baths (Chopra 1956) • Eyes leaf juice to treat trachoma (eye infection) (Anilreddy 2009). South Africa: leaf used in baths or wash for heatstroke, sunburn, heat rashes, said to be wonderfully soothing and very popular remedy (Roberts 1990). Papua New Guinea: heated leaves poulticed on boils, sores and tropical ulcers; occasionally used externally by a patient with sore anus after prolonged dysentery (sit on soft leaves for several hours) (Woodley 1991; Holdsworth & Giheno 1975) Ethiopia: commonly used for skin diseases (Teshome 2010) Philippines: humid eczema, simple ulcers (Quisumbing 1951) India: used in baths and fomentations; powdered leaves applied over wounds which are then said to heal without leaving a white scar; leaves also applied to burns and scalds (Quisumbing 1951). Pakistan: used for wound healing, treating burns and scalds, eczema and skin ulcers (Ghisalberti 1986); skin infections, particularly Tinea infections (Rajeswari 2011). Mexico: leaves for treating skin infections (Rojas 1996); gum used in decoction for treating venereal disease and leaves applied to fractures (Martinez 1959). Bolivia: Leaves poulticed on fractures, sprains, contusions; also used as a haemostatic; powdered leaves sprinkled on wounds; resin applied to wounds (Lopez-Palacios 1984). South Africa: useful for respiratory disorders: flowering plant top or leaf infusion used for treating pulmonary disorders such as croup, pneumonia, bronchitis, tuberculosis, diphtheria (Watt & Breyer-Brandwijk 1962); Bolivia: leaf and resin infusion for treating bronchitis; leaf decoction to remove phlegm (Lopez-Palacios 1984). Reunion: stem infusion used for treating lung infections, syphilis (Lavergne 1980). Other species: Ethiopia: D. angustifolia used as a wound dressing; sinusitis, rhinitis; dressing for skin diseases of the head and face; haemorrhoids (Asres 2001; Abate 1989; Lemordant 1971; Jansen 1981). Africa: D. angustifolia used to treat oral candidiasis and is reported to be more effective than commercially available mouth rinses (Mohlakoana 2010). Australia: D. polyandra: decoction of root applied daily to cuts and open wounds until healed (Isaacs 1994; Webb 1969). Investigations D. viscosa: Antibacterial studies: Mohana (2010) • leaf extracts: strong activity against Micrococcus flavus, good activity against S. aureus; also active against Bacillus subtilis, Streptococcus haemolyticus, Staphylococcus epidermis; no activity shown against Candida maltosa: extracts showed good antioxidant activity Khurram (2009) • plant extracts: antibacterial activity stronger against gram-positive (Pseudomonas aeruginosa, Bacillus subtilis) than gramnegative bacteria (E. coli, Salmonella typhi, Micrococcus luteus) Pengelly (2008); Joshi (2003) • leaf extracts: wound-healing activity; flavonoid level in leaf extracts were high enough to support this use of the herb Getie (2003) • leaf extract: antibacterial against Streptococcus pyogenes and Staphylococcus aureus Asres (2001b) • extracts did not show activity against Mycobacterium tuberculosis Ahmad (1994) • essential oil: weak level of activity against S. aureus, Bordetella bronchiseptica and Saccharyomyces cerevisiae Other species/subsp.: Teffo (2009): • D. viscosa var. angustifolia: kaempferol-related flavonoids with antioxidant and antibacterial properties isolated and evaluated. Kaempferol was, overall, the most active antibacterial component. Heymann (2009); Mothana (2008): • D. viscosa var. angustifolia extracts showed activity against S. aureus and MRSA. Asres (2001b): • D. angustifolia: dried leaf extracts did not show antimicrobial (P. aeruginosa, S. aureus); no anti-Candida or anti-mycobacterial activity Thring (2007); Mothana (2008): • D. viscosa var angustifolia: extracts showed activity against S. aureus and Candida albicans; good activity against Mycobacterium smegmatis


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Antifungal studies D. viscosa: Pirzada (2010): • leaf and shoot extracts: antifungal activity against skin fungi: Aspergillus niger, Aspergillus flavus, Paecilomyces varioti, Microsporum gypseum and Trichophyton rubrum; efficient inhibition of adherence of Candida albicans to oral epithelial cells, preventing the initial step of colonization in the process of infection; plant extracts have very high therapeutic potential at subinhibitory concentration Teshome (2010): • plant extract safety confirmed for dermal application Patel & Coogan (2008); Patel (2009); • anti-Candida activity useful for incorporation into mouth-rinses; has shown better activity than commercially available products. Rahber•Bhatti (1988) • antifungal: plant leaf decoction active against leaf rust infections in wheat Aslam (2010): • significant suppressive activity against mycelial growth of Alternaria solani and Rhizoctonia solani, suitable for development for use in agricultural crops as a fungicide. Other species: Heymann (2009): • D. angustifolia: antifungal activity Mohlakoana (2010): • D. angustifolia: extracts were negative for antifungal activity; antibacterial activity only shown against gram-positive bacteria (notably Bacillus cereus); inactive against gram•negative bacteria. Daman (2005): • D. angustifolia: antifungal activity, extracts inhibited all the strains of Candida albicans isolated from HIV positive and HIV negative patients.

Table 7.4 Additional Medicinal Uses of the Dodonaea Genus Anti-inflammatory and analgesic Traditional use D. viscosa: Leaf preparations widely utilised as an antirheumatic remedy (Samoa, Reunion, Pakistan, India, Southeast Asia, Africa) (Riley 1994; Ghisalbert 1986). South Africa: • leaves widely used for pain relief: poulticed on sore muscles, strains and other painful areas including fro the treatment of lower backache; poulticed on the back to help relieve pain of chest colds (Roberts 1990). India & Pakistan: • plant preparations widely used as anti-rheumatic remedy; leaf poultice for gout, rheumatism, snake-bite (Khurram 2009; Ghisalberti 1986; Chopra 1956); headache, backache, stomach pain, fracture pain, snake-bite pain; toothache, gum pain (Rajeswari 2011) Madagascar: leaves used for rheumatism and haemorrhoids; (Ghisalberti 1986). Peru: leaves are sour and bitter and are chewed as stimulant, like coca leaves (Quisumbing 1951); leaves also claimed to have mild anaesthetic properties (Ghisalberti 1986). Mexico: leaves used against several kinds of aches, rheumatism, swellings and for general pain relief (Rojas 1996; Ghisalberti 1986); gum used in decoction for gout, also to treat fractures (Martinez 1959). Bolivia: Leaves poulticed on injuries; resin applied to stiff joints; leaf decoction used in baths, for headaches (Lopez-Palacios 1984). Australia: leaf chewed (juice not swallowed) to alleviate toothache; chewed leaves and juice bound to wounds from stonefish or stingray (Lassak & McCarthy 1992). Other species/subsp. (or var.): Australia: D. viscosa subsp. mucronata (syn. D. petiolaris): used as a smoking medicine for internal pain; branches are laid in the warm ash pit and the patient lies over the area, in the smoke, for pain relief (Latz 1996). D. viscosa var spatulata: dried leaves burnt in a shallow pit and Dodonaea leaves put on top to produce smoke; patient sits over the smoke, lying on one side or the the other for relief of pain (Goddard 1988). D. lanceolata used as a local analgesic for pain and snake bites: leaves boiled, mashed and applied locally or taken diluted; leaves tied under the belt to reinforce the remedy’s efficacy. Also used as a warm body wash (Reid & Betts 1979; Webb 1969). D. polyandra: chewed leaf juice applied to wound from stonefish and stingray stings and bound up for 4-5 days (Isaacs 1994); used for wounds and stings; also boiled root or root juice used for toothache (listed under D. viscosa var. laurina, Webb 1969). Investigations: D. viscosa: • leaf extract: anti•inflammatory, anti•oedema activity, mild analgesic (Khalil 2006). • anti•inflammatory activity (Mahadevan 1998). • leaf extract: mild anaesthetic activity (Rojas 1996) • extracts have shown good anti•oedema, anti•inflammatory activity (Alagarsamy 2007; Vedavathy & Narayana Rao 1995). • seed extract showed significant CNS depressant activity when compared with morphine sulphate, diazepam and phenytoin as standard drugs. Significant analgesic and anticonvulsant activities demonstrated (Krupanidhi 2007). Other species: • D. angustifolia: extracts showed analgesic activity (Amabeoku 2001). • D. polyandra: investigations have shown significant anti-inflammatory potential; diterpenes with anti-inflammatory activity isolated from leaf and stem extracts (Simpson 2010, 2011).

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Antipyretic and antiviral Traditional use D. viscosa: Numerous authors mention the use of leaves as a febrifuge; wood decoction also febrifugal; India, Pakistan, South Africa, Samoa, Guam, Mexico, Taiwan, Palau (PNG), Philippines (Riley 1994; Ghisalberti 1986, Quisumbing 1951). • leaves and stems used to treat fevers and sore throat; seeds with honey used to treat malaria; root infusion for colds (Anilreddy 2009). South Africa: feverish conditions, chest colds, influenza, measles, bronchitis, pneumonia, tuberculosis; gargle for sore throat (Mohlakoana 2010; Roberts 1990). Madagascar: leaves used for fevers, sore throat and haemorrhoids (Ghisalberti 1986). Mexico: gum in decoction for fevers; timber also febrifugal (Martinez 1959). Other species/subsp.: D. angustifolia: Ethiopia – used for treating fevers including malaria, ague, sore throat, colds, influenza (Asres 2001a; Jansen 1981; Lemordant 1971). Australia: D. viscosa subsp angustissima (syn D. attenuata): cooled leaf infusion used as a wash on forehead and body to relieve fever (Lassak & McCarthy 1992). D. physocarpa and D. polyzyga: leaf and twig decoction used as body wash for relieving symptoms of colds and flu; treatment of urinary tract infection (Barr 1993) D. polyzyga: wash used for colds, flu and skin sores; odorous sticky leaves sniffed for nasal and head congestion (Wightman 1994; Smith 1993). Investigations D. viscosa: • leaf extract: antiviral activity (Coxsackie virus; influenza A virus) (Getie 2003). Other species: • D. angustifolia: leaf extracts antiviral (anti•HIV) (Asres 2001a). • D. angustifolia: extracts showed antipyretic activity (Amabeoku 2001). Gastrointestinal, antispasmodic and muscle relaxant Traditional use D. viscosa: Leaf and root preparations widely used to treat digestive system disorders: indigestion, ulcers, diarrhoea, constipation, haemorrhoids (Anilreddy 2009). Malaysia and Philippines: leaf decoction used for flatulent colic; and as a purgative (Quisumbing 1951) South Africa: astringent properties; often used as a remedy for stomach disorders; young twigs regarded as being tonic and purgative (Watt & Breyer-Brandwijk 1962); tea sipped for colic, gripe, nausea, diarrhoea (Roberts 1990). Mexico: GIT disorders incl. diarrhoea (Rojas 1996); gum in decoction also used for colic (Martinez 1959). Papua New Guinea: bark decoction taken internally as anti-dysentery remedy (Woodley 1991; Holdsworth & Giheno 1975). Investigations D. viscosa: • root extracts: significant anti-diarrhoeal properties (Rajamanickam 2010). • leaf extract: gastroprotective activity; inhibition of acid secretion (Arun & Asha 2008; Veerapur 2004). • spasmolytic, smooth muscle relaxant activity of extracts (isolation of four spasmolytic components; Rojas 1996). Anticancer and chemoprotective activity Investigations D. viscosa: • root extracts: antiproliferative triterpenoid saponins isolated; activity against ovarian cancer cells (Cao 2009). • Leaf extracts: demonstrated protection against lead toxicity; kidney and liver protective potential (Sivanesan 2009). • various plant extracts demonstrated substantial antioxidant and radical scavenging activity; flavonoids are among the active antioxidant components (Rajeswari 2011; Mohlakoana 2010; Anilreddy 2009; Mothana 2008; Pengelly 2008). • Kaempferol and methoxyflavone derivatives possess good antioxidant properties (Teffo 2009). Antidiabetic Traditional use D. viscosa: Ayurvedic medicine: root juice used for treatment of diabetes (Rajeswari 2011). Investigations D. viscosa: • leaf extracts: significant antidiabetic activity (Muthukumran 2011). • aerial parts extract: antidiabetic activity (Veerapur 2010a, 2010b). Cardiac activity Traditional use D. viscosa: India: utilised as a hypotensive remedy (Sukkawala & Desai 1962). Other species: Ethiopia: D. angustifolia used for treating angina (Lemordant 1971). Madagascar: D. madagascariensis used in popular medicine as an antispasmodic and hypotensive agent (Ghisalberti 1986).

Female disorders, pregnancy and fertility


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Investigations D. viscosa: • leaf extract: hypotensive and cardiac depressant activity; vasoconstrictor action (Sukkawala & Desai 1962). • spasmolytic, smooth muscle relaxant activity (Rojas 1996). Female disorders, pregnancy and fertility Traditional use D. viscosa: Mexico (Oaxaca): Leaves used for infertility, menorrhagia, menstrual haemorrhage, postpartum recovery and to prevent miscarriage (Browner 1985) Africa, Ghana: decoction or infusion of root bark taken to promote lactation (Abbiw 1990); root decoction also used to treat period pain (dysmenorrhoea), irregular menstruation (Anilreddy 2009). Papua New Guinea: warm solution squeezed from heated leaves applied to mother’s nipples to increase lactation (Holdsworth & Mahana 1983). Investigations D. viscosa: - leaf extract: uterine relaxant properties (Sukkawala & Desai 1962). Herbicidal and pesticidal Traditional use D. viscosa: Pulverised roots used in anthelmintic preparations; powdered leaves as a vermifuge to expel roundworms (Anilreddy 2009). Other species: Ethiopia: D. angustifolia decoction of dried fruit applied locally to treat skin parasites (ectoparasites); powder of dry fruits taken orally for lymphatic swelling (Mesfin 2009) Investigations D. viscosa: • moderate–good insect deterrent activity against a number of pests; inactive against others (Castillo 2009) • leaf extracts: potent allelopathic activity (i.e. the ability to influence the growth of other plants and organisms); flower and bark extracts had less activity (Barkatullah 2010). • leaf extract: anthelmintic, anti-ascariasis activity (Sukkawala & Desai 1962). Other species: Dodonaea angustifolia leaf extracts: pesticidal activity against American boll worm (Heicoverpa armigera); oleandrin, a cardioactive compound which has insecticidal properties was isolated (Subashini 2004).

The Stink Bug Encosternum delegorguei is a traditional delicacy in Limpopo Province, South Africa. Dodonaea viscosa var. angustifolia is a host plant for this insect, which sequesters certain chemicals. Interestingly, children in Papua New Guinea also eat the stink bugs that are found on the leaves of this shrub (Heider 1970). The leaf powder of this hop-bush has demonstrated good antibacterial properties, with various components showing activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa (Eloff 2009; Teffo 2009). (Image courtesy Cathy Dzerefos)

The red-fruited Dodonaea physocarpa is a tropical species that has been prepared as a wash in the Northern Territory for treating colds and flu (Barr 1988).

The complex chemistry of Dodonaea means that there are diverse components that could be responsible for many of their properties – and it is unlikely that any one chemical acts in isolation. The following brief summary, which outlines the most pertinent chemical

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary Thus, the triterpene saponins and the coumarin fraxetin have analgesic properties. Anti-inflammatory activity could be associated with some of the diterpenes, lupeol, oleanolic acid, saponins and flavonoids. Spasmolytic activity could arise from the presence of some diterpenes, sakuranetin, quercetin and rutin. This activity could also explain the use of Dodonaea preparations to alleviate gastrointestinal disorders. The 3-methoxyflavones could contribute to antiviral activity. The flavones hyperoside, quercetin and rutin have been shown to exert a hypotensive effect.

In addition, flavones (quercetin, oleanene glycosides) are likely to contribute to the herb’s wound-healing activity.

Dodonaea uncinata is a relatively rare species with a restricted distribution in northern Queensland.

Hop-bush in the wild, Emu Creek, northern Queensland.

compounds of pharmacological interest, is from a phytochemical review by EL Ghisalberti in 1998: The reported medicinal uses of Dodonaea species by indigenous people in different parts of the world show considerable similarities. In a broad sense, preparations were employed largely as analgesic, anti-inflammatory, spasmolytic, antiviral and hypotensive agents. Various gastrointestinal disorders, skin conditions and healing of wounds were also managed with these preparations … In considering these activities, it is possible to find a correlation with constituents, or groups of constituents.

Hop-bush for Environmental Remediation The Hop-bush is a rather important part of the native vegetation in many outback regions. It is a particularly resilient plant that readily adapts to sites that range from seaside locations to the central Australian desert. It has some remarkable environmental survival skills with a natural pioneering ability that finds the shrub springing up on mountainous sites, old lava


flows, and exposed coastal cliffs. The shrub has been widely utilised for land reclamation works: sandy sites to stop coastal erosion, and to help stabilise wet and boggy sites, or it can be planted

Hop-bush roots are extremely effective for soil conservation projects – as these wind-sheared plants illustrate, the shrub can withstand extremely difficult environmental conditions. The shrub has been widely used for binding sand, particularly for limiting beach erosion and as a fixative for sand dunes. It is also suitable for reclamation works for water-inundated sites. (Image courtesy Kim & Forest Starr, Hawaii)

 The study of the flora of many Australian arid landscapes, notably Emu-bushes and Hop-bushes, illustrates the great diversity and ingenuity of floral adaptations to an impoverished landscape. Perhaps,

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for hedges that prevent water run-off or wind erosion. It can also yield a termiteresistant hard timber that is extremely useful for fence posts.

Dodonaea viscosa under propagation for revegetation works. (Courtesy Kim & Forest Starr, Hawaii).

then, it should not be unexpected to find that many other plants from this environment have equally intriguing biochemical potential. The most interesting and surprising discoveries would certainly have been associated with a small tree of the desert which was used by Aboriginal people as both a narcotic – and a poison. This conundrum took Australian scientists the better part of a century to resolve.

Uluru or Ayer’s Rock lies at the heart of Australia’s desert landscape – an impressive landmark symbolic, in many ways, of this continent. Uluru and its immediate surrounds form a valuable ecosystem in these arid regions, hosting springs, waterholes – and unique vegetation that provides a refuge for a diversity of unique wildlife, as well as interesting bush tucker resources. Uluru is also a place of sacred sandstone caves and ancient rock art. (Image courtesy Wikipedia, Public Domain)

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Chapter 8

ANCIENT DRUGS IN A MODERN WORLD

Doctor and pharmacist, from Marsilius Ficinus, Das Buch des Lebens, Florence, 1508.

Local chemist’s building, on display at Herberton Historical Village, Atherton Tablelands, northern Queensland. Originally the ‘Apothecary’s Hall’ (established 1883) of EJ Martin at Herberton, this shop was relocated and restored, showing how an Australian pharmacy of the day would have been organised. Surprisingly, it has many characteristics that are comparable with the illustration of the pharmacy from 1508.

To some, the past uses of many medicinal plants appear to have only a vague and nebulous link with modern medicine, with our current chemical discoveries eclipsing anything that the ancients could have known. The Solanaceae family, however, provides a classic illustration of just how great a fallacy is this attitude – providing herbal drugs in antiquity that are still in use today. Many have been the mainstay of innumerable medical discoveries that continue to influence the practice of medicine. These drugs have been of practical and religious importance, probably since the very earliest experiments with the flora. Their toxicity would have been unmistakable, and their medicinal value would have been equally obvious. The story of the Solanaceae family is rife with intrigue, not only in a therapeutic sense, but also

on a chemical, toxicological and pharmacological level. The tale begins with their ancient use as drug plants and hallucinogens – potent and powerful herbs with remarkably poisonous attributes. This is as true for some Australian representatives as it was for the traditional European drugs. The cultivation of imported plants for medicinal purposes in colonial days allowed a few escapees to quickly establish themselves on the continent, among them Stramonium, a respected drug plant. For centuries members of the Solanaceae provided vital analgesics and narcotics with a profound impact on healing practices. They were among the most influential classes of drugs ever discovered. The family is an exceptionally rich source of tropane alkaloids, compounds with a potent effect on the central nervous system. The main alkaloids of medicinal interest 340


are atropine (dl-hyoscyamine) and scopolamine (hyoscine) – which are present in a number of highly effective therapeutic herbs traditionally employed in India, Asia, China, Europe and the Middle East. Some of these herbs, notably Datura and Henbane, continue to be in use.

They were originally named after their source.

Alkaloid Discoveries

Alkaloids, which are present throughout the Plant Kingdom, rate among the most influential and prolific chemical components found in the natural world. Many have potent pharmaceutical properties. Famous examples include the anticancer drug vincristine, the stimulant cocaine, the narcotic analgesics morphine and codeine, the anti-malarial agent quinine, the antihypertensive reserpine, and the anti-asthmatic ephedrine. Others are present in fungi, including the ergot alkaloids from Claviceps purpurea and the psychedelic agent psilocin from Psilocybe mexicana – while bufotenin is the toxic alkaloid from the Cane Toad (Bufo marinus). Many have poisonous side effects and herbs containing these compounds were among the most potent known in the ancient world, particularly those from the Solanaceae family. These plants have been inspirational in modern medical practice, with a flurry of alkaloidal compounds being isolated in the early 1800s.

Hyoscyamus niger, from John Lindley, Medical and Economical Botany, Bradbury & Evans, London, 1849.

Hyoscyamus niger, from Edward Hamilton, Flora Homoeopathica: Medicinal Plants used as Homoeopathic Remedies, Vol. I, Leath & Ross, London. 1852.

Hence, solanine was first isolated from Solanum nigrum in 1820. Atropine was likewise named after Atropa belladonna when it was isolated in 1831, and hyoscyamine was extracted soon afterwards from the Black Henbane (Hyoscyamus niger). Therefore it was logical that duboisine would be the name for a new alkaloid from the Australian Duboisia genus – at least until a full chemical analysis established its greater complexity. It was later found to contain a number of components, notably scopolamine.1 1 Hyoscine, a secondary metabolite of many plants in Solanaceae, was first extracted in 1880, and eight years later scopolamine was extracted from species of Scopolia. Although ‘hyoscine’ and ‘scopolamine’ are the same chemical, until the early 1920s the term used in the literature differed according to author, depending on nationality. Scopolamine ultimately took precedence in European papers – but not in England. The majority of Australian papers also stuck to the term hyoscine (Foley 2006).

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Sorcerous Solanaceae

Hag or seductress? These two images portray the great extremes of perception that have surrounded the lore and rituals associated with female ‘witch’ traditions. Left: Hexensabbat (Witches’ Sabbath, 1508), woodcut by Hans Baldung Grien; right: The Magic Circle (1886), painting by John William Waterhouse.

Commonly known as the Nightshade family, the Solanaceae contains a number of notorious herbs that earned a well-deserved reputation for ill use. These traditions were often steeped in magical lore and many tales portray their sorcerous reputation. The practice of witchcraft and wizardry by individuals wishing to influence the more nebulous planes of existence doubtless found the use of the more potent species an ‘enlightening’ experience. Esoteric experimentation has usually focused on plants with hallucinogenic attributes: Datura (Datura spp.), Black Henbane (Hyoscyamus niger), Deadly Nightshade (Atropa belladonna), Mandrake (Mandragora officinarum), and the Tree Datura (Brugmansia spp.).2

2 Even the humble Potato (Solanum tuberosum) has the potential to induce psychosis – albeit usually a result of unintentional poisoning, rather than intentional experimentation.

This fascination continues. Unfortunately, the participants usually have little knowledge of the true consequences of experimentation and reports of poisoning still occur. Recent incidents have involved a homemade stew in the US state of Maryland (CDC 2008), contaminated vegetables in Athens, Greece (Papoutsis 2010), the unwise use of some herbal medicines by the elderly in Korea (Suk & Kwak 2009), and accidental seed ingestion by children in Saudi Arabia (Al-Shaikh & Sablay 2005). Deliberate experimentation with hallucinogenic drugs has resulted in hospital admissions in Hungary (Osvath 2000), Toulouse, France (Birmes 2002), West Virginia and Iowa in the United States3 (Dewitt 1997; De Frates 2005), and Vancouver, Canada (Spina & Taddei 2007). 3 The Texas Poison Control Center reported 188 incidents of exposure between 1998 and 2004 (Suk & Kwak 2009).


Some rather bizarre accounts exist with regard to the deployment of potent Solanaceous herbs in ancient witchcraft brews and potions. Among them are records from the Spanish Inquisition. This institution was particularly fond of hunting out offenders against Church ethics – and, supposedly, extracting the ‘truth’ from its victims. The practice of witchcraft was seen as an abomination, to be rooted out of society at all costs. One telling account provides graphic details regarding the wife of an Inquisition official. She was accused ‘of being a witch and a sorceress. Her husband was exceedingly troubled at this, since he had thought her a holy woman. Then through the will of the Lord, early on Good Friday, since he could not find his wife, he went to the pigsty. There he found her naked, displaying her genitals, completely unconscious and smeared with the excrement of the pigs.’ Understandably the husband got a bit upset: ‘[he] drew his sword in sudden wrath, wishing to kill her. Returning to himself, however, he stood waiting for a little while that he might see the outcome of all this. And lo, after a little while she returned to her senses. When she saw that her husband was threatening to kill her, she prostrated herself before him and, seeking pardon, promised that she would reveal the whole truth to him.’ Unfortunately her confession did little good, as her husband promptly went and denounced her to the authorities. When they returned she was ‘nowhere to be found. They think that she drowned herself in the lake above whose shore that area is situated’ (Harner 1973). Incidentally, the old tales about witches flying were, in a sense, true. Some of their concoctions were utilised in a manner that would have been well absorbed through the skin – particularly in sensitive places such as the armpits or genitals, which allowed a rapid onset of the drug’s effects. Some herbs have highly vivid hallucinogenic properties that include the sensation of flying. Hence, the association with witches becomes obvious. Recipes generally contained at least a few of the hallucinogenic herbs already mentioned, as well as the obligatory bats’ wings (if they could catch them), and probably a poor frog too. One potion even mentioned using the fat of a dead baby to make an ointment (see Schultes & Hofman 1979). Mixtures such as this were rumoured to have been applied to the genitals – in what would appear to

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be a most unorthodox fashion. In 1324, records of a witchcraft investigation noted that ‘in rifleing the closet of the ladie, they found a Pipe of oyntment, wherewith she greased a staffe, upon which she ambled and galloped through thick and thin’. It sounds like an exceptionally wild ride. Writings from the fifteenth century recounted similar practices: ‘But the vulgar believe and the witches confess, that on certain days and nights they anoint a staff and ride on it to the appointed place or anoint themselves under the arms and in other hairy places’. So powerful were the visions from these drugs that ‘on some moonlit nights they think that they are carried off to banquets, music, dances and coupling with young men, which they desire most of all. So great is the force of the imagination and the appearance of the images, that the part of the brain called memory is almost full of this sort of thing’ (Schultes & Hofmann 1979).

Mandrake: Toxic Herb of Legend and Lore

Mandrake (Mandragora officinarum) from Tacuinum Sanitatis, a 15th century handbook of health and well-being. In the Middle Ages, when rumours of Mandrake’s deadly nature abounded, it was well known that the only safe way to pull the root out of the ground was to use a black dog tied to the plant – otherwise the scream of the root as it emerged from the earth would be lethal to those within hearing range. Of course starving the dog first, then putting food out of its reach, provided great encouragement for the animal’s efforts.

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Flowering Mandrake herb. (Courtesy Wikipedia CC-by-SA 2.5) Mandrake leaves. Accidents with misidentification and substitution of toxic plants still occur, as do incidents of psychotic poisoning associated with the contamination of vegetable greens. The isolation of atropine and hyoscyamine in samples of chard (Beta vulgaris) and spinach (Spinacia oleracea) led to the identification of Mandrake (Mandragora autumnalis) as the toxic culprit (Jimenez-Mejias 1990).

Mandrake fruit (Mandragora officinarum).

Mandrake (Mandragora officinarum), which has become naturalised throughout Europe) is a familiar herb of many ancient texts, in keeping with its widespread distribution across Europe and Asia. This plant is found from Northern Africa (Algeria, Morocco, Tunisia) and Southwest Europe (Yugoslavia, Greece, Italy, Portugal, Spain), to Western Asia (Israel, Jordan, Lebanon, Syria, Turkey). There are only two other species in the genus: the Himalayan Mandrake or Qie Shen (M. caulescens) is an Asian species (China, India, Bhutan, Myanmar,

Nepal), while the Turkmenian Mandrake (M. turcomanica) is from Turkmenistan.4 Mandrake’s legendary associations are linked to a consummate reputation as a magical and mystical agent. It has been influential in folklore and medicine since ancient Egyptian times, with the root providing a valued pain-killer, narcotic and aphrodisiac. Indeed, in ancient Greece Hippocrates (400 BC) recommended that ‘a small dose in wine, less than would occasion delirium, will relieve the deepest depression and anxiety’. In around 250 BC Theophrastus noted Mandrake was a sovereign remedy for 4 Mandragora autumnalis and M. vernalis are synonyms for M. officinarum. Mandragora chinghaiensis is a synonym for the Asian M. caulescens.


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gout, erysipelas, sleeplessness – and even for use as a ‘love potion’ (Lee 2006). In Roman times, Dioscorides described an infusion prepared from Mandrake bark strips in sweet wine for a number of months to make morion, or ‘death wine’. Mandrake was also incorporated into the narcotic mixture used for a famous anaesthetic sponge (spongia somnifera) employed by surgeons in the sixteenth and seventeenth centuries. Mandrake contains atropine and scopoletin, as well as a number of other solanaceous alkaloids.

Medicinal Solanaceae

Datura metel, white form, from Francisco Manuel Blanco, Flora de Filipinas, Gran edicion, Manila, 1880–83.

Datura metel.

Datura (Datura metel), which has long been used as a hallucinogenic and tranquillising agent, acquired a rather dubious reputation in India. Indeed the name Datura attests to the plant’s nefarious use, as it is derived from the Indian word dhat, a deadly poison used by the Thuggees (assassins). The herb was also used to drug young virgin girls and lure them into prostitution. Apparently, after their unfortunate experience, at least some of these women learned the use of the sedative properties of the herb – using it as a ‘knockout’ potion to take advantage (or not) of their clients (Duke 1985). It seems almost unimaginable that drugs destined to achieve an indispensable role in surgery would come from such an unlikely source. So exactly what were these plants and why were they so influential? Obviously their

Datura inoxia. Overall, Datura inoxia and D. metel have a very similar appearance, although the leaves of D. metel are glabrous (smooth, not hairy), while D. inoxia has a pilose character (a soft downy covering of greyish hairs). (Image on right courtesy JM Garg)

mind-altering effects led to a great deal of experimentation. It would not be surprising, then, to find that these powerful drugs had other uses, predominantly involving analgesic and antispasmodic effects.

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Perhaps the best known of the Solanaceae genera is Datura. This genus is found throughout tropical and temperate regions – with D. stramonium, D. ferox, D. inoxia and D. metel being the most widespread (often naturalised) species. The pain-relieving properties of Datura flowers in Indian and Chinese traditions are legendary. Over 1700 years ago Datura was used as an anaesthetic by the famous Chinese doctor Hua Tao. Two species predominated in medical circles: Datura metel in southern China, while D. inoxia had a more northerly distribution. These remedies were effective for cough relief, asthma, and as analgesics for treating gastric pain and rheumatism. Mixed with tobacco and Chinese Liquorice (Glycyrrhiza uralensis), the flowers provided a highly effective remedy that was smoked to treat asthma (Xiao & He 1983). Interestingly, the use of the drug plants Henbane, Datura and Mandrake as Chinese folk remedies is not only of historical interest. While modern medicine generally developed an emphasis on extracted or synthesised drugs such as scopolamine, hyoscyamine or atropine, it is important to appreciate that plantsourced remedies containing these alkaloids have continued to play a role in Chinese medicine. Their pharmacology, however, is complex.

Datura metel, purple form, from Francisco Manuel Blanco, Flora de Filipinas, Gran edicion, Manila, 1880–83. The Purple Datura (Datura metel var. fastuosa, D. fastuosa), which originates from India, has become so popular in cultivation that it is now found throughout the tropics. It is comparable to White Datura as a source of tropane alkaloids. The herb has a particularly striking appearance with its unusual double-layered trumpet flower and ebonyblack stem. There are other varieties that sport a range of coloured flowers – including blue, red and yellow blossoms.

Datura metel.

Datura metel ‘Black Currant Swirl’, unopened flower. (Courtesy Wikimedia Commons Project).


Black Datura (Datura metel var. fastuosa). (Courtesy David Dickerson, CC-by-SA 3.0 Unported)

A Potent Anti-asthmatic and Anaesthetic

Datura metel, from Hans-Simon Holtzbecker, Gottorfer Codex, 1649–59.

Flowers, while often neglected as medicinal agents, can have a potent pharmacological effect. Datura metel is illustrative. Interestingly, this ancient anaesthetic herb has continued in practical modern use. The plant is highly effective in its herbal form, which has been preferred by some practitioners over the extracted alkaloids. The leaf and seeds have substantial antispasmodic and bronchodilatory activity, while the dried flower can be smoked with tobacco for the relief of asthma. Datura flowers are highly effective analgesics, useful for the relief of myalgia (muscular pain), numbness and rheumatism – while the juice was squeezed into the ear to ease an earache. Extracts of the flowers, injected or taken orally, have been used for surgical operations in China. The dose of 3–5 g within 5 minutes induced anaesthesia which lasted 5-6 hours (Duke & Ayensu 1985). The Reverend GA Stuart outlined the traditional preparation of this herb in his Chinese Materia Medica of 1911: ‘If equal quantities of this [herb] and of Cannabis sativa are gathered in the seventh and eighth moons, dried in the shade, pulverized, and digested in wine, the preparation when ingested, will produce a narcotic anaesthesia that will enable small operations and cauterizations to be done without pain’.5 The herb also had antibacterial and antifungal properties. Decoctions of the root, leaves and flowers were regarded as being useful for treating boils, ringworm (a fungal skin problem) and other skin infections (dermatophytosis), and as a remedy for rabies. The Reverend Stuart commented: ‘The flowers and seeds of the Man-t’o-lo [Datura alba] are used in medicine as a wash for eruptions on the face, oedema of the feet, and prolapsus of the rectum. They are prescribed also for colds, chorea, nervous disorders, and their use as an anaesthetic is also mentioned. Their deliriant action is also spoken of, being said to produce laughter or dancing movements.’ Doubtless it was extremely effective for many of the conditions mentioned. 5 Reverend Stuart’s work was a revision and extension of an earlier publication on the subject by Dr F Porter Smith.

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The Black Henbane (Hyoscyamus niger)

Henbane: flowers and fruiting shrub. Hyoscyamus tincture for pharmaceutical use. Harvesting Henbane for medicinal use requires collection of the best quality undamaged leaves, which are gathered when the plant is in full flower and dried immediately to retain their chemical integrity. (Image from Herberton Historical Village, Atherton Tablelands, north Queensland) Apothecary vessels for the storage of Hyoscyamus from the 19th century, displayed at Deutsches Apothekenmuseum Heidelberg, Germany. (Courtesy Andreas Franzkowiak, Halstenbek Germany: Wiki-pedia user Bullen-wächter)

The Henbanes, notably Black Henbane (Hyoscyamus niger) and White Henbane (H. albus), have long been utilised as magic, medicinal and hallucinogenic herbs in Europe and the Far East. Certainly, Henbane was one of the herbs used by witches to spike their potions. Official acknowledgment of the potent effects of these herbs can be found in documents that date from antiquity. The famous Greek physician Dioscorides (AD 40–90), a military surgeon under Nero, mentioned Hyoscyamus albus, the use of which

was attended with great caution. His masterful work on herbal medicine (AD 70–80) formed the basis of European medical pharmacopoeias for the next 1500 years. Henbane was mentioned in Anglo-Saxon medicinal works and in the tales of the Arabian Nights. One of the oldest of the Chinese herbals, Sheng Nung Pents’ao Jing (22–250 AD), outlined the use of Hyoscyamus niger. Henbane’s medicinal use is based on its analgesic, antispasmodic and narcotic effects – and it was traditionally utilised in the treatment of asthma, gastralgia, neuralgia, pertussis (whooping cough) and epilepsy. The seed, which had a similar reputation, was also applied as an analgesic for toothache. The herbalist John Gerarde (1597) mentioned its sedative and analgesic effects: ‘Henbane causeth drowsinesse, and mitigateth all kinde of paine: it is good against hot and sharp distillations of the eye and other parts. The leaves stamped with the ointment Populeon, made of Poplar buds, assuageth the pain of gout. To wash the feet in the decoction of Henbane causeth sleepe … The leaves, seed, and juice taken inwardly cause an unquiet sleep like unto the sleepe of drunkenesse, which continueth long, and is deadly to the party.’

Juice of Hyoscyamus, from additions of 1874 to the British Pharmacopoeia, 1867.

Henbane had rather spectacular anaesthetic effects – although Gerard mentions another use that is decidedly puzzling: ‘[to] cause worms to come forth of the teeth, by burning it in a chafing dish of coles, the party holding his mouth over the fume thereof: but some crafty companions to gain money convey small lute-strings into the water, persuading the patient, that those small creepers came out of his mouth or other parts which he intended


to ease’. Such descriptions titillate the imagination! Atropine, hyoscyamine and scopolamine are classed as anticholinergic drugs. Their importance lies in their antispasmodic activity, which is excellent for the treatment of spasmodic pain of the gastrointestinal and genitourinary tracts – as well as an antisecretory effect that reduces nasopharyngeal and bronchial secretions, salivation, or excessive perspiration. Anticholinergic agents are particularly applicable for surgical procedures. During general anaesthesia they prevent muscle spasm and reduce secretions. In addition, they can decrease vagal nerve stimulation and acid secretion, thereby having an antiulcer effect. Various other conditions that have been successfully treated by this class of drugs include the relief of arterial spasm, fainting due to heart block, gangrene, enuresis (bed wetting), and some eye disorders (inflammation of the

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cornea or iris). Atropine has valuable properties useful for treating heart rhythm problems (bradyarrhythmia, sinus bradycardia) and hypotension accompanied by a slow heart rate – as well as effective antiviral, antiemetic, and antidiarrhoeic properties (Duke & Ayensu 1985).

Stramonium in Australia

Datura stramonium, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1897. Also known as Jimson Weed or Stramonium, this Solanaceae herb contains atropine, hyoscyamine and scopolamine.

Weedy Datura

Belladonna, from Edward Hamilton, Flora Homoeopathica: Medicinal Plants used as Homoeopathic Remedies, Vol. I, Leath & Ross, London, 1852. The principal alkaloids of the herb (leaf and flowering tops) are hyoscyamine and hyoscine (scopolamine), from which drug supplies were sourced preWorld War II.

The European genus Datura is a major source of tropane alkaloids (atropine, hyoscyamine, hyoscine). There are fourteen species, six of which are found in Australia.6 All are introduced and are considered to be weeds. Even the herb known as ‘Native Thornapple’ (Datura leichhardtii) was an early immigrant that settled in the inland regions of Queensland and South Australia. 6 The additional species are: D. ceratocaula, D. discolor (Desert Thornapple), D. kymatocarpa, D. lanosa, D. pruinosa, D. quercifolia (Oak-leaf Thornapple), D. reburra, D. velutinosa. Brugmansia is a South American genus that was formerly classified as Datura (Luna-Cavazos & Bye 2011).

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Datura wrightii is a North American species that has been utilised as a sacred hallucinogen. (Courtesy Dane Larsen, Wikimedia Commons Project)

Datura ferox has distinctive large prickly seed capsules. As a weed, it can form unpleasant thorny thickets with nasty elongated spines that are extremely sharp and penetrating. This nuisance weed is widespread throughout eastern Australia (Queensland, NSW, Victoria, Tasmania), ranging to central Australia (Northern Territory, South Australia). It is also found to a limited extent in Western Australia. The other immigrants are the Fierce Thornapple (Datura ferox), the Angel’s (or Devil’s) Trumpet (D. metel), the Downy Thornapple (D. inoxia syn. D. meteloides), the Common Thornapple (D. stramonium), and the Hairy Thornapple (D. wrightii): • Datura ferox is widespread along the eastern coastline, ranging from Tasmania to northern Queensland. • Datura metel and D. wrightii are fairly uncommon. • Datura stramonium is predominantly found

Native Thornapple (Datura leichhardtii) is present throughout much of continental Australia, although it does not extend to southwest Western Australia, coastal New South Wales, Victoria or Tasmania. Datura leichhardtii is an odd case of an American species being described from Australia, where it is introduced. Although subsequently described from its native range under another name, the earlier name of leichhardtii has priority. (Image courtesy J Miller ©Centre for Australian National Biodiversity Research)

Unripe and ripe fruit of Datura metel. (Image on left courtesy Thamizhpparithi Maari, Wikimedia Commons, CC-by-SA 3.0 Unported; image on right courtesy Pancrat, Wikimedia Commons)


The sharply spiked fruits of Datura inoxia differ from the knobby fruits of D. metel. Officially, Datura seeds are sourced from the hyoscine-containing Datura metel. In contrast, Datura ferox seeds contain hyoscine and meteloidine as the major alkaloids. (Images of seeds courtesy Philippe Marin, Wikimedia Commons)

in Victoria and New South Wales, although it has occasionally spread into other states. • Datura inoxia is primarily a weed of New South Wales and Western Australia (southwest, northern regions) – although it does range into the other mainland states, except Victoria. More than a century ago Stramonium became naturalised in Australia. Its prolific spread into the countryside quickly ensured its reputation as an invasive weed. In 1880 the botanist FM Bailey noted: ‘Among the Solanaceae we have a goodly number of naturalized plants. The common thorn apple (Datura stramonium Linn.) has become a great nuisance in all the colonies ... more in Queensland than elsewhere. It has been thought to have caused the death of stock now and again; but I imagine such instances must be rare, as it is seldom eaten by stock. The harm it does is the room which it takes up, which would in most cases be otherwise occupied by good grass.’ However, Mr Fred Turner, Department of Agriculture botanist, New South Wales, regarded its toxic properties as a far more serious matter: ‘When growing in pastures it is really a dangerous weed, for I have known it to poison milch cows that have partaken of it, and no pains should be spared on the part of any one who keeps cattle to exterminate it from grazing lands. When it is allowed to grow undisturbed for a time it produces a phenomenal quantity of seed, which will, when ripe, germinate readily any time during the summer months whilst there is moisture in the soil, so that the area of its occupation gradually widens from year to year.’ It continues to be considered a noxious

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pest – with its medicinal reputation largely forgotten. Stramonium has been valued as an anti-asthmatic remedy since ancient times. Turner noted: ‘I have very often given the leaves of the “thorn-apple plant” to persons suffering from asthma, and recommended them to smoke it – but with caution, and not too often – as they would tobacco, and when they have done so it has given them great relief. When used for this purpose the leaves should be partially dried in some place away from the influence of the sun’s rays’ (Turner 1891). He related some early clinical experiences with the herb: [its use] has received somewhat striking confirmation from Mr. John Price, of Penrith, who, according to a letter addressed to the Department, experiences immediate relief from smoking the dried leaves made into cigarettes. His son, a lad, sometimes suffers most violent attacks of asthma, and on such occasions a powder prepared from the midrib of the leaves, and dried seeds from the pods mixed with nitre, is at once brought into use. A little of the powder is ignited, and the fumes gently inhaled through a funnel, with astonishing results. The fame of these remedies appears to have spread over a great portion of the Colony, as he has been applied to for the latter preparations by persons at Mudgee, Bathurst, Goulburn, and Kiama. He is constantly giving some of the powder to neighbours, and it seldom fails to afford relief. This confirmation is satisfactory, but at the same time the caution given [previously] … should not be overlooked (Turner 1891).

At a time when little else was available for the treatment of asthma this testimony would have been a great boon to sufferers of the disease. Dr. Nelson’s Improved Inhaler was invented by its namesake in the early 1860s. It was widely stocked by pharmacists during the late 1800s and early 1900s as a method of drug administration as per instructions printed on the apparatus. (Image from The Apothecary, Cairns, courtesy Tony Young) (Right) Stramonium tincture, manufactured by Drug Houses Australia.

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Advertisement for Dr. Batty’s Asthma Cigarettes. Although the exact ingredients are not stated, and remain a bit of a mystery, they may well have included Stramonium as a bronchodilator. (Image from Herberton Historical Village, Atherton Tablelands, north Queensland) Stramonium, from Rembert Dodoens, A Nievve Herbal, or Historie of Plantes, Gerard Dewes, 1578.

There was ever-present concern about the serious side-effects of tropane alkaloids. Plants containing scopolamine and hyoscyamine are decidedly toxic, with numerous incidents of inadvertent poisoning being recorded over the centuries. In 1676 the toxic reputation of Jimson Weed or Stramonium (Datura stramonium) became well publicised after an incident in America. At a place called Jamestown, soldiers mistakenly ate the leaves as a vegetable, with many suffering psychosis. This scandalous incident hit the headlines, as the following graphic description by Robert Beverley (1705) shows: The James-Town Weed (which resembles the Thorny Apple of Peru, and I take to be the Plant so call’d) is

supposed to be one of the greatest Coolers in the World. This being an early Plant, was gather’d very young for a boil’d Salad, by some of the Soldiers sent thither, to pacific the Troubles of Bacon; and some of them eat plentifully of it, the Effect of which was a very pleasant Comedy; for they turn’d natural Fools upon it for several Days: One would blow up a Feather in the Air; another wou’d dart Straws at it with much Fury; and another stark naked was sitting up in a Corner, like a Monkey, grinning and making Mows at them; a Fourth would fondly kiss, and paw his Companions, and snear in their Faces, with a Countenance more antick, than any in a Dutch Droll [sic]. In this frantick Condition they were confined, lest they should in their Folly destroy themselves; though it was observed, that all their Actions were full of Innocence and good Nature. Indeed, they were not very cleanly; for they would have wallow’d in their own Excrements, if they had not been prevented. A Thousand such simple Tricks they play’d, and after Eleven Days, return’d to themselves again, not remembring any thing that had pass’d.


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convulsive coughs, pertussis (coughing) associated with bronchitis or influenza, and as an expectorant for stubborn phlegmatic conditions. However, although the activity of Stramonium8 is almost identical to that of the Deadly Nightshade (Atropa belladonna), the former had a better reputation as an antispasmodic drug. Therefore its efficacy in the treatment of asthma would not be unexpected. The fact that it was widely distributed throughout Australia, whereas Belladonna was not, also ensured a ready availability of the drug.

Datura stramonium and Mandrake fruit, from John Lindley, Medical and Economical Botany, Bradbury & Evans, London, 1849.

Sounds like there was a bit of a mess to clean up afterwards! No wonder the herb quickly gained a widespread infamous reputation – acquiring the name ‘Devil’s Apple’. The toxic effects can be distressing: dry throat, giddiness, delirium, hallucinations and mania, staggering gait, dilated pupils, vision and speech disturbances. Incautious experiments can result in a comatose state and numerous fatalities have been recorded. Understandably, Stramonium is no longer recommended for general therapeutic use, although it was listed in the British Herbal Compendium of 1992 as an antispasmodic and anti-asthmatic agent7 (Bradley 1992). Official recommendations have included its use for the treatment of asthma, 7 Hyoscyamus leaf (Hyoscyamus niger) and Belladonna (Atropa belladonna) are also listed in the BHC (1992) with full details of herb constituents and dosage requirements.

Atropa belladonna. A single fruit of Belladonna, or Deadly Nightshade, can contain around 1 mg atropine. As the safe dose is around 1.5 mg, two fruits would be considered a toxic risk, especially for a child – and, even at the accepted dose, many individuals would experience anticholinergic side-effects of varying intensity: pupil dilation, flushing, dry mouth, fast heart beat (tachycardia), confusion, agitation and hallucinations. Children have died from doses as low as 0.2 mg/kg atropine (Ulbricht 2004).

8 The antispasmodic agent scopolamine butylbromide is a later derivative that could be safely used without risking the side-effects associated with these drugs – disorientation, hallucinations and memory loss (Grynkiewicz & Gadzikowska 2008).

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Datura stramonium var. tatula. The leaf and flower of this herb have been utilised as a cataplasm, decoction or poultice (in some places with grease or coconut oil) for treating cancer, inflammatory tumours and tumours of the feet (Hartwell 1971). (Image courtesy Skapperod, Wikimedia Commons, CC-by-SA3.0 Unported)

Given its psychotic reputation, it may be somewhat unexpected to find that the sedative effects of Datura stramonium were once widely used in the treatment of mental disorders and as an anticonvulsant in epilepsy. The basis of this was linked to its scopolamine content9, which has a central nervous system depressant activity, whereas atropine had a stimulant effect. Scopolamine could therefore be used for calming delirium, for sedation prior to anaesthesia, and to induce obstetric amnesia in combination with other painkillers, thereby inducing a useful form of ‘twilight sleep’.10 Scopolamine’s relaxant properties were instrumental in the development of some infamous ‘truth drugs’ used in Inquisition-style investigations. It relaxed a person virtually into a mood of insensibility and in large doses could markedly influence suggestibility. Interrogators took advantage of this confused state of mind to gain the victim’s cooperation. However, these drugs can have disastrous consequences, particularly for those affected by psychosis, with subsequent 9 The chemical scopolamine is also relatively abundant in Datura fastuosa var. alba and D. metel (see Table 8.1). 10 Scopolamine has been used in experimental investigative studies as it can induce temporary memory loss. It has thus been found useful to model the dysfunction associated with ageing and dementia, and is thereby employed in testing protocols for new drugs that affect the central nervous system (Grynkiewicz & Gadzikowska 2008).

amnesia. A particularly harrowing tale illustrative of the extreme hazards of these drugs involves a young man who experienced a bout of delirium leading to self-amputation of the tongue and penis after taking Angel’s Trumpet (Brugmansia sanguinea): ‘He was immediately transported to the University Surgery Hospital, but a re-implantation of the amputated parts was impossible. Approximately 24 h after the self-amputation, the young man was examined by a psychiatrist from our team. The patient reported a complete amnesia for the time between going to bed and waking up from the surgical operation in the hospital. No other psychopathological symptoms were registered during the psychiatric investigation 24 h after the event’ (Marneros 2006).

The Toxic Angel’s Trumpet

Ornamental Angel’s Trumpet cultivar.

Angel’s Trumpet or Tree Datura is a tropical garden ornamental from the genus Brugmansia with a hallucinogenic reputation that has led to experimentation – albeit inadvisable. Tree Datura has a similar chemical makeup to that of the Datura herbs (containing a wide range of


tropane alkaloids), with equally toxic potential. Intoxication can result in violent convulsions and a deep comatoselike torpor, with extreme discomfort for those who wake. So effective was the stupor that the drug was once given to the wives and slaves of dead chieftains of the Colombian Chibcha tribe, Brugmansia sanguinea. before they were buried alive. In the Andes and in the western Amazon it has been used in the preparation of ritual hallucinogens designed to facilitate communication with the ancestors. Brugmansia sanguinea has been well respected throughout the region as a potent medicinal plant.

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Brugmansia sanguinea (B. bicolor), from PJA Drapiez, Dictionnaire Classique des Sciences naturelles, 1853 (hosted by Villanova University Digital Library).

Old Herbs for New Drugs

Table 8.1 Solanaceae Herbs Utilised as Medicinal Plants or for Drug Production Species (distribution) Atropa belladonna Belladonna, Deadly Nightshade Central and Southern Europe, Asia Minor Widely cultivated: England, Germany, India, USA

Chemical components (Evans 2002) Official ‘Prepared Belladonna herb’ refers to the finely powdered drug, which is standardised to contain 0.28– 0.32% alkaloids. Dried leaf and flowering tops: 0.3–0.6% total alkaloids. Main alkaloid: hyoscyamine. Belladonna root: alkaloids 0.4–0.6%. Hyoscyamine (main alkaloid), plus atropine and scopolamine.

Substitutes (similar constituents): Atropa acuminata Indian Belladonna, Himalayas of northern India Other tropane alkaloids are Atropa baetica Southern present: Spain and northern Morocco apoatropine, belladonnine and derivatives, which also have influential pharmacological attributes.

Medicinal uses and notes • A tropine has stimulant effects on the nervous system, although it can depress the nerve endings to secretory glands and muscle (Evans 2002) • Plant extracts: component alkaloids have a synergistic effect. Secondary components may have antagonistic or synergistic activity. High doses have depressant action on the CNS, while low doses tend to stimulate (Izaddoost & Robinson 1987). • Improves speech and gait in Parkinson’s disease while reducing tremor and rigidity (Bradley 1992). Clinical use: • Atropine has been utilised to treat gastrointestinal spasm (gastritis, enteritis, hyperacidity), asthma (as an antispasmodic), and arrhythmia due to bradycardia (slow heartbeat), influenza (anti-viral action) (Duke & Ayensu 1985). • Apoatropine has shown greater activity than atropine as an antispasmodic agent (Izaddoost & Robinson 1987). • Additional constituents:

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary • F lavonoids (quercetin, kaempferol etc.) with antispasmodic and diuretic activities; chlorogenic acid, which has central nervous system stimulant actions, as well as antihistaminic and antibacterial properties (Izaddoost & Robinson 1987). • Coumarins: scopoletin and scopolin (Bradley 1992). • Dosage: British Herbal Pharmacopoeia (up to three times daily): dried herb 50 mg infusion; 1:10 tincture 0.5 ml (Bradley 1992). • Belladonna (plant/leaf, root, flowers, fruit) has been utilised since ancient times as a folk remedy for numerous forms of cancerous skin growths, ulcers and wounds; particularly breast and uterine cancer (Hartwell 1971).

Brugmansia sanguinea and other species; Tree Datura South America (Andes: Colombia to Chile) Datura fastuosa (formerly classified as D. metel) Double-flowered Purple Datura

Hyoscine-rich: 0.8%. • Hyoscine does not have the central stimulant effects of atropine, Wide range of tropane alkaloids possessing a more sedative effect (Evans 2002). • B . sanguinea has been cultivated in Ecuador as a commercial source of scopolamine (Schmelzer & Gurib-Fakim 2008). Main alkaloid: hyoscine. Traces: hyoscyamine and atropine.

Note: Over 20 different species of Datura have hallucinogenic properties. The related genera Brugmansia, Brunfelsia and Solandra contain similar tropane alkaloids (see Griffin & Lin 2000). Datura ferox Main seed alkaloids: hyoscine and meteloidine. Datura metel Total leaf alkaloids: 0.5%. Hindu Datura Main alkaloid: hyoscine. Traces: hyoscyamine and atropine.

Datura inoxia

Datura stramonium Stramonium Europe: Origin: Caspian Sea Naturalised: Europe, North America Cultivated: central Europe, South America Widespread weed

• C linically scopolamine (as hyoscine hydrobromide) has been valuable for preventing the nausea and vomiting associated with motion sickness (Evans 1998). • Hyoscine hydrobromide: has been used as pre-operative medication, with papaveretum, prior to anaesthesia. • Anticancer remedy: leaf and fruit poulticed on cancerous/ malignant or inflammatory tumours (Hartwell 1971).

Alternative source of hyoscine.

• Commercial source of ‘datura leaf’. • Traditional use: hallucinogenic, analgesic and tranquillising agent. The flowers of Datura metel are officially recognised in the Chinese Pharmacopoeia. • Flowers, leaf and seeds: primarily employed as a bronchodilatory ‘Datura seeds’: agent, spasmolytic (spasm-relieving) and analgesic (Duke & Total alkaloids: 0.2%. Ayensu 1985; Xiao & Hu 1983). Primarily hyoscine, with traces • Leaf: bronchodilatory action in asthma; antispasmodic for of hyoscyamine and atropine. spastic cough. • Flower: applied externally for pain relief (myalgia, numbness); dried and smoked for asthma. • Flower, root and leaves: treatments for skin disorders (skin infections, boils, ringworm), rectal prolapse, rheumatic pain, anti-asthmatic, rabies. • Flower extracts: used as an anaesthetic in Chinese hospitals, taken orally or injected; it has also been combined with chlorpromazine as an anaesthetic (Duke & Ayensu 1985). • Anticancer agent: use of fruit or leaf poultice malignant tumours; also seed decoction in vinegar (Hartwell 1971). Total alkaloids: 0.5% (leaf). • Commercial source of ‘datura leaf’. • Anticancer remedy: plant or leaf cataplasms (sometimes with coconut oil, grease or butter) applied to tumours (Hartwell 1971). Total alkaloids: 0.2–0.45%. • Ancient use as a toxic hallucinogen. Main component: hyoscyamine • Hyoscyamine-based activity almost identical to that of the (0.25%). Deadly Nightshade (Atropa belladonna) – although it was Hyoscine, possibly small considered less constipating, more sedative to the central amounts of atropine. nervous system, and had a stronger action on the respiratory tract. • The sedative effects of Stramonium were formerly regarded as useful for the treatment of conditions such as epilepsy, mania and even insanity – although the results were not reliable, possibly due to chemical variations of the herb.


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• • • •

British Herbal Pharmacopoeia (Bradley 1992): Dried leaf, 50–100 mg, taken direct or as an infusion. Prepared Stramonium BP (0.25% total alkaloids) 50–200 mg. Stramonium Tincture BP (1:10, 45% alcohol) at a dose of 0.5–2.0 ml. Note: Recommended doses must be strictly adhered to as poisoning can easily result from the use of this herb. • Anticancer uses: plant/leaf employed as ointments, plasters, cataplasms and poultices for cancerous conditions: ulcers, breast tumours, inflamed tumours (Hartwell 1971). Duboisia myoporoides, and D. leichhardtii Duboisia leaf

Main leaf alkaloids: hyoscyamine and hyoscine.

Australia Hyoscyamus niger Henbane Prepared Hyoscyamus BP: 0.05–0.07% alkaloids: England, Europe, eastern (hyoscyamine and hyoscine). Asia, northern Africa Leaves: hyoscyamine (0.045– 0.14%). Cultivated: former Soviet Substitutes: almost identical Union, Balkans, Belgium, alkaloid content. England, Germany, USA Substitutes: Hyoscyamus alba Continental Europe (particularly France), India

Other species such as H. aureus and H. pusillus produce hyoscine as their principal alkaloid.

Hyoscyamus reticulatus Indian Henbane India, Pakistan

Hyoscyamus muticus Egyptian Henbane India, Upper Egypt (native) Algeria (introduced) Mandragora caulescens Mandrake

Total alkaloids: Leaves – 1.7%. Flowers – 2.0%. Stems – 0.5%. Smaller amounts: hyoscine and apoatropine. Hyoscyamine and scopolamine as major alkaloids (Xiao & He 1983).

• Numerous minor alkaloids present. • Different chemical races occur (see Chapter 10 for details).

• Ritual toxic hallucinogen. • Activity: Hyoscyamine-based drug that resembles Belladonna and Stramonium, albeit weaker. Contains higher proportion of hyoscine, resulting in less cerebral excitement than Belladonna (Evans 2002). • Toxicity: Side-effects of the drug were rarely encountered although high doses can have hallucinogenic effects. • Medicinal use: anti-hidrotic and antispasmodic. Primarily used for relief of cramping and spasm of urinary and gastrointestinal tracts, including the prevention of intestinal griping due to purgatives. Traditional use as a sedative in nervous disorders and for mentally disturbed patients (Evans 2002; Duke & Ayensu 1985; Grieve 1931). • Chinese medicine (Duke & Ayensu 1985): • Leaf and flowering top of herb: analgesic, antispasmodic, and sedative agent for treating gastralgia, neuralgia, coughing, sciatica, rheumatism and asthma. • Seed: asthma cough, epilepsy, myalgia (muscle pain), toothache. • Anticancer agent: Henbane has had an extensive history of use in the treatment of cancer. The leaf was poulticed onto skin growths, tumours, indurations, cancerous wounds and breast lumps, and numerous other types of tumours – e.g. face (mouth, gums), parotid gland, tumours of extremities (knees, legs, feet), bladder, scrotum, inguinal region; sclerosis of the liver or spleen; condylomata of the anus (Hartwell 1971). Note: Grieve (1931) has an extensive section on the medicinal uses of Hyoscamus niger. • Source of hyoscyamine, used for production of atropine (Evans 2002). • Important medicinal plant in Egypt (Grieve 1931). • Formerly used for drug production by the British during World War I. • H ighly toxic reputation: ‘It is exceedingly poisonous, and is used to destroy birds and beasts, especially rats and other vermin’ (Stuart 1911). • Medicinal use: sedative in coughs, angina and colic; parasiticide in parasitic skin disorders (Stuart 1911). • Recommended in Yunnan and Tibet as a tonic as the roots are similar to Ginseng. The herb has antispasmodic properties that were valued for treating gastrointestinal disorders (Xiao & He 1983).

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Mandragora officinarum syn. M. autumnalis True Mandrake Europe, Mediterranean

Scopolia japonica Japanese Belladonna Japan and Korea Scopolia lurida (syn. Anisodus luridus) China Scopolia tangutica (syns Anisodus tanguticus, Prezwalskia tangutica) Nepal, Tibet, China Substitutes: Scopolia caucasica, Scopolia carniolica Europe, Russian Federation

Atropine, scopoletin (a fluorescent compound) and various other alkaloids (Evans 2002). Hyoscyamine, scopolamine and mandragorine (Tyler 1988)

Steroidal glycosides (scopoloside).

Main alkaloid: hyoscyamineyielding species (very similar to Belladonna). S. tangutica: total alkaloids 1.7–3.8%, high content of hyoscyamine, varied amounts of other alkaloids: anisodamine, scopolamine, anisodine (daturamine), cuscohygrine.

A Modern Market

The market in tropane alkaloids continues to be substantial. Old and new products employ tonnes of atropine and scopolamine, which are extracted from genetically modified plant cultivars – and demand for these drugs is growing. Chemical and biotechnological advances continue to increase the drug yield. Production levels for the international market are given below (2005 figures, from Grynkiewicz & Gadzikowska 2008): • Scopolamine: around 600 kg (sales around US$77 million). • Atropine: 1,000 kg (sales: US$131 million).

• Ritual hallucinogen and toxin. • Formerly leaves and roots official in the pharmacopoeias of Spain and France (Evans 2002). • Root (chewed): ancient physicians used root as simple painkiller and anaesthetic prior to surgery. • Root (juice extracted from bark, given in wine or water): used as a sedative for insomnia, painful conditions, mania, melancholia, convulsions. • Leaves (infused and ointments): local application to ulcers, ugly scars, inflammation, rectal suppository (Le Strange 1977). • Anticancer: the herb (the leaf and root) utilised as an anticancer fomentation or cataplasm for numerous form of tumours (scirrhous, inflammatory or indolent tumours; indurations, hardness, knots, kernels) (Hartwell 1971). • M. autumnalis poisoning: classic symptoms of flushing, mydriasis, tachycardia, blurred vision, difficult micturition, dizziness and headache. Less common symptoms included vomiting, difficulty swallowing, abdominal pain, skin and mucosal dryness (e.g. mouth dryness), as well as nervous system problems or mental distress (hyperactivity, hallucinations, psychosis, agitation or delirium) (Jimenez-Mejias 1990). Treatment: Prostigmine or physostigmine. The latter gave a better response with regard to psychoneurological problems (JimenezMejias 1990). Dried rhizomes official in Japanese Pharmacopoeia 1961 (Duke & Ayensu 1985). • Chinese medicine (Duke & Ayensu 1985; Xiao & Hu 1983): • Various species utilised for treating injuries, rheumatic pain, and gastrointestinal spasm • Roots: used as an analgesic, anaesthetic, antispasmodic, and anti-oedemic remedies. • Effective for pain relief: biliary ascariasis, cholelithiasis and gastroenteritis (chronic or acute). Externally, used to treat ulcers and to reduce ‘swelling’. Intoxication: symptoms similar to those of Belladonna (Atropa belladonna) poisoning: dilation of pupils, initial dryness of the mouth (later frothing occurs), mental disturbances. It is, however, less toxic than atropine. As with scopolamine, anisodine and anisodamine have been used experimentally to induce amnesia.

• Hyoscyamine: production is less, 140 kg (sales: US$67 million). Other tropane alkaloid-derived drugs continue to be of importance in the marketplace11 (Grynkiewicz & Gadzikowska 2008): • Tropisetron: an important synthetic anti-emetic useful in cancer chemotherapy and radiotherapy; also has an anti-inflammatory action with potential for immunomodulation in inflammatory disorders. • Benztropine: antiparkinson agent. • Deptropine: antihistamine.

11 Anisodamine (see page 359) is an Asian drug that is not currently on the international market.


• Ipratropium bromide: synthetic bronchodilator (production: 2,000 kg per annum, with a value of US$1.7 billion). • Tiotropium bromide: synthetic bronchodilator used as a maintenance treatment in chronic obstructive pulmonary disease (production 12 kg per annum; value US$1.2 billion).

Chinese Drugs from Scopolia

Japanese Scopolia (Scopolia carniolica).

Scopolia lurida.

Scopolia podolica.

Chinese medicine traditionally utilised species of Scopolia12 which are closely related to their Solanaceous European counterparts. This genus illustrates the potential value of clinical drug developments that can be derived from 12 Closely related genera such as Prezwalskia and Atropanthe contain similar alkaloidal constituents.

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modern research into age-old remedies. The alkaloids anisodamine and anisodine (and related compounds) have antispasmodic properties comparable to atropine, although their anticholinergic effects are weaker. Studies have investigated the use of these compounds in thrombosis, stress ulcers, cerebral ischaemia (reduced blood flow), nerve injury pain, endotoxaemia, pulmonary damage, and to support cardiovascular (myocardial) function following burns and ischaemia. The alkaloids have the benefit of being fairly non-toxic due to their quick metabolism in the body – they are readily absorbed from the gastrointestinal tract without being destroyed and are rapidly excreted in the urine, therefore the incidence of toxic side-effects is minimised (Chai 2000; Sheng 1997; Su 1992; Duke & Ayensu 1985; Xiao & Lu 1983). (6-hydroxy-hyoscyamine) • Anisodamine has an excellent effect on improving microcirculation in the body, particularly following shock. It has been effectively used for treating explosive deafness, gangrenous complications in diabetic patients, and is extremely valuable for severe burns patients. It is highly effective for restoring the intestinal circulation during shock and the prevention of gastrointestinal complications in conditions such as bacillary dysentery, meningitis, haemorrhagic enteritis, or following sepsis in burns cases. Its antispasmodic activity is better than atropine, with an equivalent spasmolytic activity, although the drug is less active on nervous system function (Liu 1996; Li 1994; Duke & Ayensu 1985; Xiao & Lu 1983). • Anisodine (daturamine, hydroxy-hyoscine) is an effective detoxicant for organic phosphorus compounds (pesticides), with less side-effects than atropine. Clinically it has been used for treating migraine, a form of vascular spasm of the eye (involving the fundus oculi), eye trauma, some forms of paralysis due to neurological disorders, and as an anaesthetic (Zhu 1996; Xiao & Hu 1983). • Anisodamine hydrobromide has given good

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experimental results in acute ischaemic renal failure, and has been found clinically valuable for the treatment of snakebite in combination with an antivenin. The drug reduced the incidence of renal failure, bleeding, and microcirculatory collapse (Li 1999; Liu & Zhang 1998).

Physostigmine: From Potent Poison to Invaluable Medicine

Physostigma venenosum is a woody climber of swampy riverbanks that was formerly utilised as a highly toxic ordeal poison. The ‘Ordeal Bean’ was the dried ripe seed – physostigma is a Greek term referring to its bladder-like appearance, and venenosum means ‘full of poison’.

Another important aspect of these ancient drugs should be addressed at this point. The development of medicinal plants as anticholinergic agents was linked to the story of another infamous plant, Physostigma venenosum. This poisonous vine of the Fabaceae family was the origin of physostigmine – a drug that was to play a vital role in surgical procedures, and opened the way for the discovery of effective treatments for glaucoma and neurological disorders such as myasthenia gravis (a rare form of progressive muscular paralysis). Abdominal operations became safer with its use because it could prevent the intestinal gas accumulation that was an extremely hazardous side-effect of surgery. Later, physostigmine and its derivatives were to prove valuable as neuromuscular blocking agents, which were an essential adjunct to the use of anaesthetics. Their antagonistic effects stimulated recovery from the latter, acting to prevent (as well as remedy) post-operative intestinal atony and urinary retention. Acetylcholine is a major chemical messenger at nerve endings and its effects on the nervous system are highly influential throughout the body. Without a working knowledge of the role of cholinesterase, the task of unravelling the seemingly mysterious mechanisms of the nervous system would have been far more difficult. The Martindale Extra Pharmacopoeia (1952) noted the following important details regarding the pharmacology of these discoveries: Physostigmine acts by inhibiting cholinesterase, thus preventing the rapid destruction of acetylcholine produced in the body as a result of cholinergic nerve impulses. Thus it allows acetylcholine to exert all its characteristic effects in an intensified manner, including its muscarinelike [muscarinic] effects on smooth muscles, glands and heart and its nicotine-like [nicotinic] effects on skeletal muscles and autonomic ganglia. The main physiological actions of physostigmine are its miotic [pupillary contraction] action, its action on the gastro-intestinal tract of increasing tone and motility, and its action in causing fibrillary twitching of skeletal muscle.

It can also reduce blood pressure (via arterial dilation) and reduce the heartburn associated with pregnancy. Unsurprisingly, physostigmine (and its


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derivatives) were not devoid of toxic sideeffects – which were almost the opposite of those experienced with the use of the tropane alkaloids. The Martindale Extra Pharmacopoeia of 1952 explained: The symptoms of poisoning by physostigmine are restlessness, weakness, nausea, vomiting, sometimes purging, epigastric pain, rarely miosis [constriction of the pupil]; salivation, sweating and lachrymation [watering of the eyes], palpitation with slowed pulse, dyspnoea, muscular twitching all over the body,

convulsions and collapse. The skin becomes ashen-grey in colour. Consciousness is not affected except for faintness and a feeling of impending disaster. Death may occur within half to two hours from the time symptoms are first noted, and is usually due to either pulmonary oedema or central respiratory paralysis. Atropine quickly counteracts the serious effects on lungs and circulation but it does not influence the muscular twitchings, which are not serious and which subside as the drug is eliminated from the body.

The Infamous ‘Ordeal Bean of Old Calabar’

Calabar Bean. (Courtesy Tracey Slotta @ USDA-NRCS PLANTS Database)

Calabar Bean and Physostigmine Sulphate from the British Pharmacopoeia of 1867.

The origins of the drug physostigmine and its development as an anticholinesterase agent lie with the notorious reputation of the toxic Calabar Bean on the Nigerian Calabar coast – a vine that was grown

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exclusively for use in trials seeking ‘truth and justice’. Possession of the poison was restricted to chiefs, who sat as judges during public hearings. Naturally, its use was traditionally associated with great power. Most of the complaints involved accusations of witchcraft – a very pervasive cultural belief. Those charged with such misdemeanours had to undergo an ordeal trial utilising the poison. In 1846, a report by the British Army surgeon William Daniell triggered interest in the effects of the Calabar Bean. He wrote of a court system where: ‘every prisoner suspected of capital offences is brought, to undergo examination and judgement. If found guilty, they are usually forced to swallow a deadly potion, made from the poisonous seeds of an aquatic leguminous plant, which rapidly destroys life.’ It appears that the chances of survival were regretfully slim. While many died, some had a lucky (if somewhat messy) escape if they vomited up the brew. This reflex reaction could sometimes expel enough of the toxic potion to forestall their demise. If they survived the terrifying experience they were declared innocent of any misdemeanour. Understandably, while fear and superstition were powerful forces in this society, charges of witchcraft were not made lightly. Equally damaging counter-charges were always possible and the accuser, as well as the accused, could easily end up undertaking the ordeal. A few years after William Daniell’s report, the Professor of Materia Medica and Therapeutics at Edinburgh University, Robert Christison, undertook some personal experiments with the bean – and almost killed himself in the process. His experiments were recorded in detail and clearly outlined its great potency. Even a minor dose resulted in ‘a certain pleasant feeling of slight numbness in the limbs, like that which precedes the sleep caused by opium or morphia’. The next morning, just to make sure he had the right plant, he took a calculated risk and doubled the dose. He initially experienced a slight giddiness which he ‘ascribed to the force of the imagination’. However, the reaction proceeded to intensify: ‘The giddiness was then very decided, and was attended with the peculiar indescribable torpidity over the whole frame which attends the action of opium and Indian hemp in medicinal doses. Being now quite satisfied that I had got hold of a very energetic poison, I took immediate means for getting quit of it, by swallowing the shaving

water I had just been using, by which the stomach was effectually emptied. Nevertheless I presently became so giddy, weak and faint, that I was glad to lie down supine in bed’ (Christison 1855). Unfortunately, he absorbed enough of the poison to cause further discomfort. His symptoms continued to worsen and within forty minutes he became: ‘very prostrate and pale, the heart and pulse extremely feeble and tumultuously irregular; my condition altogether very like that induced by profuse flooding after delivery; but my mental faculties quite entire’. Unable to move, he was fully alert despite his indisposition: ‘the mental faculties unimpaired, unless perhaps it might be that I felt no alarm where my friends saw some reason for it. I had, in fact, no uneasy feeling of any kind, no pain, no numbness, no prickling, not even any sense of suffering from the great faintness of the heart’s action; and as for alarm, though conscious I had got more than I had counted on, I could also calculate, that, if six grains had no effect, twelve could not be deadly, when the stomach had been so well cleared out.’ While he found himself decidedly weak the following day, after a night’s sleep awoke and felt ‘quite well’. The dose used in the ordeal trials was far greater – acting to paralyse the respiratory muscles, with the victim dying of asphyxiation. Not a pleasant death.

Discovery of a Miracle Drug

Close to two decades later a potent active principle was isolated and named physostigmine. Experiments on eye function eventually discovered that the drug had excellent potential for preventing blindness due to glaucoma. The discovery of its value in surgery quickly followed. However, almost another century was to pass before the Ordeal Bean contributed another remarkable therapeutic breakthrough in the medical world. In 1934, a London doctor, Mary Walker, noticed a resemblance between myasthenia gravis and curare poisoning. The antidotal property of physostigmine on curare13 (another notorious plant-based poison) inspired Dr Walker to try physostigmine on her myasthenia gravis patients. 13 Curare is a South American arrow poison, sourced from Strychnos toxifera and the vine Chondrodendron tomentosum it kills by inducing respiratory paralysis. The isolation of a potent muscle relaxant, d-tubocurarine, from these sources was to later inspire numerous drugs utilised for surgical procedures that could minimise the amount of anaesthetic required. Physostigmine is antidotal to its effects.


Physostigmine Salicylate, from the British Pharmacopoeia, 1932.

She achieved some remarkable results – much to the chagrin of some of her colleagues. Unfortunately, her work was largely ignored by the profession, although her outstanding successes could not be disregarded indefinitely. Experiments eventually extended the use of the drug to conditions with nervous involvement such as tetanus, chorea, colic, tic (nervous twitches) and epilepsy. The 1941 Martindale Extra Pharmacopoeia further explains the use of physostigmine for treating myasthenia gravis: ‘Physostigmine, being a partial

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antagonist to curare, was tried in the hope that it would counteract the effect of the unknown substance which might be exerting the curare-like effect on the myoneural junctions [nerve endings in muscles]. Hypodermic injections of physostigmine salicylate were found to have a striking though temporary effect. Injections of 1/60 gr. [grain] once daily were of value, but effect wore off in 2 to 4 hours. Greater improvement with 1/50 gr., lasting 4 to 5 hours. M. B. Walker, Lancet, i/1934.’ Later, physostigmine salicylate was successfully employed for the treatment of the painful muscle spasm associated with fibrositis, bursitis and rheumatoid arthritis: ‘It causes relaxation of muscle spasm which may even have persisted for many years. The effect of a subcutaneous injection is rapid, occurring 3 to 15 minutes after administration, and may persist for several days. It does not produce any severe toxic reactions’ (Martindale 1952). Mary Walker’s work was a great achievement that offered myasthenia gravis sufferers their first hope of relief from the disease. Importantly, she initiated a new field of research with promise for many neurological diseases that continues to influence treatment protocols to this day (Keesey 1998). The early investigation of physostigmine derivatives spurred on chemical efforts in drug development that were extraordinarily influential. The discovery of prostigmin was one of these: ‘A synthetic peristaltic stimulant allied to physostigmine, but stable in solution and safer in use. It is given by subcutaneous, intramuscular or intravenous injection in postoperative intestinal paresis [partial paralysis], severe constipation, retention of urine, myasthenia gravis etc.’ Given orally it could result in severe poisoning, hence injectable forms were recommended as they allowed greater control over the dose. The benefits ‘surpassed anything experienced with other methods of treatment’. This was an important improvement: ‘From the practical point of view it is now possible to abolish the more serious symptoms and to keep the patients in a tolerable state of health by means of ephedrine and eserine or Prostigmin [neostigmine]’ (Cooke & Passmore 1936). Although these drugs did not work for every patient, they provided a great deal of relief in a majority of cases. The discovery of acetylcholinesterase inhibitors revolutionised many areas of medicine, particularly

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the treatment of neurological disorders, due to their dramatic effects on the nervous system. Physostigmine derivatives were proposed for use in Huntington’s chorea (a progressive degenerative neurological disease characterised by muscle twitching and nervous tics). Other drug developments followed. Neostigmine, which was derived from physostigmine, was less likely to cause gastrointestinal upset. Unfortunately, when neostigmine was trialled for treating myasthenia gravis, side-effects limited its use, even though it gave better results. Further research led to more effective analogues of the drug. Of these pyridostigmine, which was developed in the 1950s, proved to be an extremely valuable drug that is still used today. Furthermore, these discoveries were linked to the development of antidotal chemical warfare agents. Pyridostigmine has successfully been deployed as a prophylactic agent against nerve gas attack and was employed during the Persian Gulf War. It continues to play a role an essential emergency clinic drug for treating organophosphorus poisoning – as well as being used to treat other forms of curariform drug toxicity and muscle weakness in myasthenia gravis patients. Acetylcholinesterase inhibitors also have memory enhancement attributes and have been utilised for the treatment of Alzheimer’s disease.14

nerves, in relation to the heart, ganglionic transmission, neuromuscular transmission, vasodilator fibres and sweat fibres. It also contributed much to the understanding of the function of the blood brain barrier [which prevents many chemicals entering the brain]. Physostigmine has also been the subject of classical experiments with atropine and curare on pharmacological antagonism.

Anticholinesterase Agents for Memory

Enhancement

Drugs for Memory and Warfare

In an extensive review of the Ordeal Bean, Bo Holmstedt (1972) provides a good overview of the medical and chemical importance of cholinesterase: Again, one is struck by the screening abilities of so-called primitive people. If attention had not been focused early on the ghastly poison ordeal of the Efik people of Old Calabar, it seems very likely that our present knowledge of many basic mechanisms in physiology and biochemistry would have been considerably retarded. Physostigmine was the first alkaloid proven to act through inhibition of an enzyme. Knowledge of its action made possible the development of a successful bioassay for the neurohumoral transmitter [nervous system chemical] acetylcholine. Indeed, the alkaloid has contributed most to the understanding of neurohumoral chemical transmission and mapping out of cholinergic 14 An example is the drug cymserine (and derivatives) with similar effects to physostigmine (via increasing brain acetylcholine levels) as well as reducing levels of the biomarkers of Alzheimer’s disease in the brain.

Galanthus woronowii. (Courtesy Alexander Klink, Wikimedia Commons, CC-by-SA 3.0 Unported)

Alkaloids with anticholinesterase activity are a relatively rare resource in the plant kingdom. After the discovery of physostigmine another century was to pass before a herb was found that contained these compounds. A Russian screening program discovered that the Caucasian Snowdrop (Galanthus woronowii), in the family Amaryllidaceae, yielded a chemical called galanthamine, which had excellent potential for treating neurological problems. Other sources of galanthamine (or galantamine) included similar small herbs known as ‘snowdrops’: Leucojum aestivum


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havhave reduced quantities of the specific Clinical trials of galanthamine found it could significantly assist memory retention, as well as help to prevent the rapid degeneration of recall functions – at least in the short term. The drug was well tolerated with only a few side-effects, primarily of a gastrointestinal nature. Fortunately, their incidence decreased with long-term use. The drug also has analgesic properties similar to those of pyridostigmine (Zarotsky 2003; Maelicke 2000; Maelicke & Alburquerque 2000; Raskind 2000; Tariot 2000; Bachus 1999; Iliev 1999; Nordberg & Svensson 1998; Sharma 1997; Fulton & Benfield 1996; Harvey 1995; Cozanitis 1983).

Leucojum aestivum, from Johann Georg Sturm, Deutschlands Flora in Abbildungen (Painter: Jacob Sturm), 1796.

from the Black Sea and Ungernia victoris from southern Central Asia. The alkaloid was found to be more widespread than first suspected in the Amaryllidaceae (genera Crinum, Galanthus, Hymenocallis, Hippeastrum, Leucojum, Lycoris, Narcissus, Pancratium and Ungernia). The anticholinergic and anticholinesterase properties of galanthamine prompted its use in treatments for myasthenia gravis, myopathy and a range of nervous complaints. In particular, interest focused on its potential for the treatment of dementia and memory impairment. In Alzheimer’s disease, patients have reduced quantities of the specific chemical receptors for nicotinic acetylcholine in the brain. Cholinesterase inhibitors help to correct the balance. However, because these drugs have a generalised action on the entire nervous system there can be undesirable side-effects, and the search for improvements in therapy continues.

The development of physostigmine analogues had profound consequences for the progress of warfare. Sadly, the chemical discoveries that resulted from the investigation of physostigmine were to lead to some highly undesirable, and very influential, developments. This involved the production of organophosphorus compounds that inspired chemical warfare agents – as well as a diverse range of potent and potentially dangerous insecticides. Of particular concern was the development of compounds with the ability to temporarily block the action of the cholinesterasebased enzyme system. This prevented the degradation of acetylcholine in the body with consequent adverse effects on the entire nervous system. Walter Sneader (1985) writes in detail of the chemical developments surrounding anticholinesterase agents. Once the chemistry of this process was determined it was only a matter of time before fluorine-containing organophosphorus compounds were found that formed a permanent bond: Under these circumstances, acetylcholine cannot be broken down and nervous transmission is disrupted. This inevitably results in death. The lethal action of such organophosphorous compounds has been ruthlessly exploited in the development of war gases with the terrifying potential to kill entire populations. The initial discovery of these loathsome agents was purely accidental. At the University of Berlin, in 1932, Willy Lange and his student Gerda von Kreuger took advantage of the recent availability of fluorine to prepare the first phosphorusfluorine compounds. In the course of their work they experienced marked pressure in the larynx, followed by

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breathlessness, clouding of consciousness, and blurring of vision.

At the time, this work was briefly mentioned in a chemical paper. The potential value of these compounds as insecticides was quickly appreciated. They were deemed to be of particular interest in Germany where alternatives to nicotine, an imported drug, were being sought. Nicotine’s insecticidal properties were based on imitating the activities of acetylcholine and a consequent disruption of the insect nervous system. Anticholinesterase compounds were subsequently manufactured, and in large quantities: As the war clouds gathered, their potential as chemical warfare agents was fully appreciated by the German authorities, who stockpiled them for military use. The first agent to be so Representation of the acetylcholinesterase (ACh) enzyme. Inhibitors of employed was tabun … Described as a ‘war this enzyme have profound effects on neurological function. They are gas’, it was actually a liquid that could be used in the development of drugs for treating memory and neurological deployed in a fine dispersion. A plant disguised disorders, insecticides and neurotoxins. Some naturally occurring as a soap-making factory was opened near the venoms and poisons also have ACh-inhibitory effects. (Image courtesy Polish border in 1942 for production of tabun. jag123, Wikimedia Commons, Public Domain). By the end of the war, twelve thousand tons During the Second World War extensive research had been manufactured, and field forces were equipped with tabun-filled shells. The far more toxic was directed toward analysing the biochemistry of sarin was developed in 1938; a mere one milligram of atropine and hyoscyamine, ostensibly for their use this was capable of killing an adult within minutes after as mydriatics and surgical drugs. Atropine was not being absorbed through the skin. In the early fifties, the only employed in ophthalmology at that time, it also United States supplied its chemical warfare units around played an essential role in surgical procedures. The drug the world with sarin, under the code name of GB. Later was indispensable in operating theatres treating the in the decade, production began of the even more toxic casualties of war because it counteracted the effects of VX agent (Sneader 1985).

In Britain dyflos (diisopropyl-fluorophosphate: DFP) was found to be the most toxic of the anticholinesterase compounds discovered by Lange and Krueger. Despite this, after the war dyflos was occasionally used for the treatment of glaucoma. The treatment of the traumatic effects of chemical warfare was likewise inspired by chemical discoveries relating to the neurological effects of tropane alkaloids. Atropine and scopolamine demonstrated significant protective actions against chemical warfare agents, notably those with anticholinesterase activity. This antidotal effect reduced the toxic impact of fluorophosphonate-based chemicals and reduced the recovery time following exposure.

neostigmine and physostigmine. However, secret experiments were undertaken with far more sinister intent. The toxicological potential of atropine was under investigation – both as an antidote to, and as a weapon of, chemical warfare. Fortunately, physostigmine was found to be an effective antidote for chemicals with atropine-like activities. It inhibited acetylcholine breakdown and was therefore able to prolong and enhance the effects of this chemical in the body. Even so, it was a drug to be used with extreme care. Side-effects from high doses included tremors, ataxia and hallucinations, central nervous system depression, sleep, and possibly death due to respiratory failure. It use is now recommended only in emergencies.


Mushroom Toxin Antidotes

Pesticide being prepared for large-scale spraying. There are serious concerns about the toxicology of many pesticidal compounds, hence the full protective suit and gloves. (Image courtesy USDA)

Pesticides that were developed from the study of anticholinesterase agents later revolutionised farming practices throughout the world. They have also been widely used in manufacturing processes – e.g. as solvents or plasticisers. However, even low doses can be toxic, with particular effects on neurological function. They have been widely responsible for both deliberate and unwitting toxicity and environmental disruption since their discovery. Indeed, studies have indicated links between organophosphate pesticide exposure, chronic fatigue and carcinogenic potential. There are very real concerns regarding an increased risk of Alzheimer’s disease and childhood developmental problems such as ADHD (attention deficit disorders) from dietary exposure due to residual toxins, even at very low levels, in crops sprayed with these pesticides.

Amanita muscaria, from Edward Hamilton, Flora Homoeopathica: Medicinal Plants used as Homoeopathic Remedies, Vol. I, Leath & Ross, London, 1852.

Fly Agaric (Amanita muscaria).

The Fly Agaric mushroom (Amanita muscaria) is a decorative toadstool with a long history of causing poisoning – as well as being a potent hallucinogen that can have unpleasant sideeffects in store for the participant.

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The primary toxins in the Amanita genus are amatoxins and phallotoxins, with the latter being poorly absorbed and thus rather less toxic. Other chemical classes of interest include tryptamines and alkaloids (e.g. ibotenic acid). In particular, the alkaloid muscarine is chemically similar to acetylcholine (Dewick 2002; Evans 2002). While Fly Agaric poisoning is not generally fatal, it can be highly discomforting. Unfortunately, the symptoms of poisoning, which include muscular twitches, slow pulse rate, breathing difficulties, delirium and coma, are often considerably delayed, by which time the condition is difficult to treat. Poisoning can be antidoted by the use of atropine (Evans 2002). However, poisoning due the closely related Amanita phalloides, the Death Cap mushroom can be lethal due to its high amatoxin content, the fatal dose being 5–7 mg. A single Death Cap mushroom contains 7 mg and the fatality rate is high, at 30–60 per cent (Dewick 2002). Irreversible liver and kidney failure

Death Cap Mushroom (Amanita phalloides). This mushroom is a common find in Victoria (particularly in Melbourne’s suburbs) and Canberra. Unfortunately it is easily confused with the edible Straw Mushroom – and merely one Death cap can kill. In January 2012 two people died after eating toxic mushrooms at a New Year’s Eve party (Canberra Times, 4 January 2012). (Image courtesy Ron Wolf )

are the primary complications. If given early enough, intravenous infusions of silibinin (a natural flavonolignan complex from the Milk Thistle, Silybum marianum15), can protect against liver failure, increasing the chance of survival and reducing the necessity for liver Death Cap Mushroom warning sign in Canberra. transplants.

(Courtesy Ayarctas, Wikimedia Commons, Public Domain)

15 Silibinin also has excellent prospects for use in protecting the liver from the side-effects of cancer chemotherapy (Greenlee 2007; Tamayo & Diamond 2007).

 The medical discoveries associated with the tropane alkaloids and physostigmine were to underpin many subsequent advances in surgery and emergency medicine. These particular links led to later discoveries from the Australian flora, notably in the native Duboisia genus (Solanaceae family). In many ways, the effects of these trees were not totally unexpected, given their illustrious herbal relatives. There were also toxicological implications which were intimately bound to an appreciation of the age-old traditions associated with the use of the ancient Solanaceae herbs. Even so, Duboisia was to present a unique botanical and scientific puzzle – the investigation of which proved to be a complicated and frustrating task. The pharmacology of the genus was particularly challenging due to elusive chemical differences between plants that were difficult to pin down. Ultimately, it was discovered that different chemical varieties (chemovarieties) existed. Their investigation was to highlight the extraordinary chemical complexity that could be associated with natural products. It was also a valuable lesson in the essential role that in-depth biochemical evaluation played in enabling commercial drug development from the native flora.

Chapter 9

PITURI: A MYSTERIOUS NARCOTIC

The Australian continent is characterised by a great diversity of habitats and equally diverse floral components. Special features include the remarkable wildflowers of Western Australia and impressive great expanses of rugged coastline. (Images courtesy Mark Maupin, flickr)

The first half of the twentieth century saw the potential of the native Australian flora as a drug resource become the subject of serious investigation. An essential prerequisite of the quest, however, was to ensure the correct identity of the eligible species. This logical starting point was to prove a herculean task, fraught with practical difficulties due to the very nature of the unusual flora of the continent. Joseph Banks and Daniel Solander had struggled with this problem from their first sightings of the east coast, while even earlier William Dampier had been intrigued by the strange forms and unusual flower colours he encountered on the west coast.

Chemist’s shop at Herberton Historical Village, North Queensland, named for the pharmacist who set up the original ‘Apothecary’s Hall’ in the town in 1883.

Once begun, the floral investigations resulted in the identification of many new genera – a task that continues to this day. Of course, at the time, the practical value of so many new and unique plants remained a mystery. However, the story associated with the discovery of one of our most influential natural drugs, was to involve a tale of chemical and botanical intrigue that harks back to the ancient use of the Solanaceae drug plants. Strangely enough, the successful evaluation of some plant-based drugs in Australia was to be

While numerous prepared drugs were originally imported from overseas, Australia developed a thriving pharmaceutical industry that utilised both imported and local raw materials. (Herberton Historical Village, Atherton Tablelands, north Queensland) 369

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facilitated by World War II – a conflict that served as a catalyst for the phytochemical study of the native flora. At the time, the major European pharmaceutical supplier was Germany, which meant that the outbreak of war had a catastrophic effect on the provision of essential medicinals such as opium, digitalis, hyoscine (scopolamine)1, belladonna and ergotamine. The search for alternatives became a priority across the world. Somewhat unexpectedly, particular importance became attached to the investigation of an Aboriginal drug known as ‘pituri’ – a popular narcotic harvested from a desert tree that belongs to the Solanaceae. 1 Scopolamine and hyoscine are interchangeable terms. Early studies often referred to it as hyoscine (hence the predominance of this term in the text), although more modern papers use the term scopolamine.

Australian Erythroxylaceae

The shrub Erythroxylum australe ranges from southern Queensland to the northern parts of the state. (Courtesy Mark Marathon, Wikimedia Commons, CC-by-SA 3.0 Unported)

Early investigations into the Australian flora initially focused on species that belonged to plant families with known medicinal properties. Not only were members of the Solanaceae of interest, there were also three Erythroxylum species from the Coca family2 (Erythroxylaceae): • the Queensland Erythroxylum australe; • Kerosene Wood or Turpentine Tree (Erythroxylum ellipticum) which favours the northern tropics (Western Australia, the 2 This should not be confused with the Cocoa tree, Theobroma cacao (family Malvaceae), the source of the cacao bean which is used to produce chocolate.

Northern Territory and Queensland); • Brown Plum (Erythroxylum ecarinatum), which is restricted to the wet tropics rainforest of northern Queensland. Despite the fact that these three species have a famous South American relative – Erythroxylum coca, the source of cocaine – none has any history of use as a stimulant or analgesic, although there have been rumours to the contrary. Professor Len Webb (1948) commented of the Brown Plum (Erythroxylum ecarinatum), ‘some forestry workers in North Queensland believe this tree contains cocaine, apparently basing their belief on a botanic affinity to the species yielding the cocaine of commerce’. The reputation appears quite undeserved. Investigations of Erythroxylum australe did not detect any cocaine, although a coca-tannic acid, as well as a cocaine-like alkaloid (0.8% meteloidine in the leaf ) were isolated. This is really not so surprising. Cocaine is only produced in any quantity from cultivated plants: Erythroxylum coca (0.23–0.96%), E. novogranatense (0.47%), and its variety truxillense (0.76–1.02%). Because the latter is also rich in methylsalicylate, this led to its use in cocaflavoured drinks. However, close relatives in the wild are devoid of cocaine, or it is present only in minute amounts (0.0005%). The Amazonian Coca (E. coca var. ipadu) also has a low cocaine content (less than 0.4%) (Griffin & Lin 2000). Although once used as a local anaesthetic with a useful vasoconstrictive activity that limits bleeding from an injury, cocaine has not been widely acceptable as a medicinal drug due to its extremely high addictive potential – but it has inspired research that led to the discovery of important anaesthetics devoid of this sideeffect. Cocaine synthesis and the subsequent development of anaesthetic drugs began in the late 1800s.3 Many medical experiments were undertaken in the early 1900s, when its 3 The alkaloid name ‘cocaine’ is derived from its botanical source, the Coca bush (Erythroxylum coca). Originally this compound was isolated in 1855 by a German chemist and identified as erythroxyline. Refined cocaine was produced in 1860 by another German, Albert Nieman.


addictive nature quickly became manifest. Amylocaine was discovered in 1903 and used for spinal anaesthesia. In 1905 the local anaesthetic procaine (novocaine) was developed, which remains in use today – although alternatives such as lignocaine or lidocaine (Xylocaine) are now commonly employed in clinical practice. Benzocaine is another important anaesthetic that originated from this research. The leaves of the Australian Brown Plum (Erythroxylum ecarinatum) contain alkaloids, although little intensive investigation appears to have been done to clarify their chemistry. In Papua New Guinea the leaf was chewed with a traditional form of salt and the sap swallowed for the treatment of stomach upsets. It has also been utilised to stop vomiting. In India a related species, Erythroxylum monogynum, has been similarly used for gastrointestinal upset and as an anti-emetic (Holdsworth & Sakulas 1986).

Erythroxylum coca seedling and E. novogranatense seeds. (Images courtesy Farmer Dodds, flickr)

The Brown Plum (Erythroxylum ecarinatum) is a tropical species that grows up to 20 metres high, forming part of the rainforest canopy. This rare shrub of northern Queensland ranges to Papua New Guinea and the fabled ‘Spice Islands’ of the Celebes and Ambon. The tree was once harvested for its durable timber, which was useful for making tankstands and fencing posts. The small orange fruits are favoured by fruit-pigeons during December to April. They are very sticky when crushed, emitting an aroma of green beans.

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An Outback Drug Plant

Early outback explorers mentioned the use of an unknown herb as a chewing substance by Aboriginal people – a habit that was widely practised across the continent. This piqued the curiosity of the scientific community. Even in 1770, James Cook had recorded its use: We observd that some, tho but few, held constantly in their mouths the leaves of an herb which they chewd as a European does tobacca or an East Indian Betle.4 What sort of plant it was we had not an opportunity of learning as we never saw any thing but the chaws which they took from their mouths to shew us; it might be of the Betle kind and so far as we could judge from the fragments … but whatever it was it was used without any addition and seemed to have no kind of effect upon either the teeth or lips of those who used it (quoted in Beaglehole 1963).

It took almost a century before the drug plant known as ‘Pituri’ became the subject of serious investigation. In 1861, the ill-fated Burke and Wills Expedition recorded experiences with this narcotic. On May 7th, at Cooper Creek, Wills wrote in his diary: ‘In the evening, various members of the tribe came down with lumps of nardoo [Marsilea drummondii] and handfuls of fish, until we were positively unable to eat any more. They also gave us some intoxicating stuff they call “bedgery” or “pedgery”5; it has a highly intoxicating effect when chewed even in small quantities. It appears to be the dried stems and leaves of some shrub’ (Maiden 1889). The only survivor of this expedition, John King, brought back some ‘pitcherry’ which was presented to the Royal Society of Tasmania in 1863. A letter from a Dr Murray, published in the 18 January 1879 issue of the Lancet, provided further details: King … who had lived seven months with these natives when rescued by Howitt, states that when his food became so scarce and bad as barely to support life, he sometimes obtained a chew of pitchiri, which soon caused him to forget his hunger and the miseries of this position. It also plays an important part in the social rites 4 Piper betle (Betel), from the Pepper family (Piperaceae), is a viny shrub whose leaves have been chewed as a mild stimulant throughout Asia. Betel Nut, which is used as a narcotic masticatory in some parts of India, Southeast Asia, Malesia and the Pacific Islands, is a different product sourced from the palm Areca catechu that stains the teeth brown. The nut (the palm fruit) may be wrapped in Betel leaves for chewing purposes. 5 The spelling can differ in early writings, with the name also written as ‘pitchiri’ or ‘pitcherry’.

Burke’s Tree, near Innamincka Waterhole, Cooper Creek, 1935. The remains of William O’Hara Burke were interred here on 21 September 1861 by the Victorian Relief Expedition led by Alfred William Howitt. (Image from Frank Clune’s collection of lantern slides for his lecture series and publications about the Burke & Wills Expedition, 1860–1861.) (nla.pic-vn3506797-v) of these natives. At their ‘big talks’ and feasts the pitchiri ‘quid’ – for I can find no more appropriate word for it – is ceremoniously passed from mouth to mouth, each member of the tribe having a chew, from the pin’arco, or head man, downwards. This singular wassail cup never fails to promote mirth and good fellowship, or to loosen the tongues of the eloquent. I have not been able to ascertain if the excitement it produces can be pushed to actual intoxication, or whether natives suffer from its use. There is a curious mode of greeting on Cooper’s Creek. When friends meet they salue [sic; greet each other] with ‘gaow, gaow’ (‘peace, peace’), and forthwith exchange pitchiri ‘quids’, which when well chewed are returned to their owner’s ears! They extend this custom to us; but the fullest appreciation of their hospitality in offering their highly-prized and indeed only stimulant could never overcome our repugnance to the nauseous morsels hot and steamy from their mouths. I may add, they always accepted our want of politeness good-humouredly. The ‘quid’ which I have spoken of, which is carried behind the ear, is composed of pure pitchiri, green leaves, and woodashes. The pure pitchiri6 I saw resembled unmanufactured tobacco of a very coarse kind, dried and pulverised. It had the same brownish colour; but the stalks and midribs, which were strong, preponderated over the finer parts of the leaf. I could never obtain an unbroken leaf nor even a good piece of one as a specimen. It had no particular smell, but a most pungent taste, which to me appeared like tobacco, and chewing it promoted a copious flow of saliva. The natives take a good pinch of pitchiri, and knead it with green leaves (quoted in Bancroft 1885). 6 Although some ‘Native Tobacco’ herbs (genus Nicotiana) were called Pituri, for the purposes of this discussion the term is used only to describe Duboisia hopwoodii.


Joseph Maiden (1889) also mentioned the drug: This is the masticatory of the aborigines of Central Australia, corresponding in this respect to the ‘Coca’ of Peru, the Hashish of India, the Betel Nut of the Eastern Archipelago, the ‘Taezi Kaat’ (Catha edulis) of Arabia, &c. The drug is in the form of leaves, more or less powdered, mixed with finely broken twigs, forming altogether a brown herb. So fine is the powder, and so irritating, that the most careful examination of a specimen is attended with sneezing. The plant is, as far as known, extremely patchy in distribution, and the blacks prize it so highly that they travel enormous distances to procure it; besides, it is a most valuable commodity for tribal barter. They gather the tops and leaves when the plant is in blossom, and hang them up to dry. They are sometimes sweated beneath a layer of fine sand (W. O. Hodgkinson), dried, roughly powdered, and then packed in netted bags, skins, &c., for transport. In Northern Australia the bags are made from the split young leaves of Pandanus aquaticus F.v.M. , according to a specimen in the Kew Museum. I have examined dozens of packages of Pituri at different times, and they have all been made of netted work or canvas. Every bag appeared to be precisely the same both in size, pattern and material. The material I believe to be obtained by the aborigines from gunny-bags or woolpacks; these are unpicked, woven into circular mats about 6 inches [15 cm] in diameter, and folded over the contained Pituri like a jam-tart. The bag is then sewn up with fibre of the same material.

Pituri: Trade Across a Continent

The trade of Pituri was a complicated affair, as the North Queensland writer, Mr JR Chisholm, recorded: In the pituri country (the watershed of the Mulligan) the indigenous blackfellow has none of the questionable comforts of the white man. His revenue is derived from

Aboriginals in the Outback. Postcard from collection of photographs from Marjorie Bell’s trip around Australia, 1928–1929. (nla.pic-vn3098515-v)

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the pituri tree growing on the summit of his sandhills. He gathers it, chaffs it, and then bags it and makes his trade with his nearest neighbours, taking in exchange such as they have to offer – perhaps weapons made from the timber of another towrie – notably the heelaman or shield made from a species of currajong; or perhaps he takes flint knives or the white brush tails of a species of marsupial rat used in lieu of cockatoo feathers at corroboree decorations; or if he can get it, some article of wearing apparel is very dear to his heart. I once gave a myall tribe a pair of moleskin trousers. I think within the two days I stayed near them, every blackfellow had a turn out of them, and no doubt among that tribe, even to this day, those trousers are a pleasing reminiscence, and so the trade goes on. What opium is to the Chinaman, what whisky is to the Scotchman, so is ‘pituri’ to the western blackfellow. It is his very soul – without it he has no life almost. As I have said, in these trading transactions profit is lost sight of; they seek none. The intermediate tribes are ‘on velvet’ minus cost of carriage. Thus – I trade my blanket for a bag of pituri to you. You take from it your own requirement for the year; you carry it across your towrie of 100 miles [160 km], more or less, and there you trade what is left, for similar value, to your neighbours; they in turn do likewise, and so on, and on, until there is none left.

The addictive attributes of the drug were very real: ‘The tribes on the borders of the trade never get enough, and with them it is a chronic state of crave, crave. Once, years ago, I carried for novelty a small sack full of pituri “Inside”, as far as the Landsborough River. I showed it to the blacks there, and although I had intended it for my scientific friends in Sydney, I parted with it; I could not stand the continual begging of the Landsborough blacks. I was besieged for it, they offered me all they possessed—weapons, piccaninies [sic], gins.’ The Northern Protector of Aboriginals, Walter Roth (1901), provided a detailed description of pituri preparation: After roasting in the ashes the pituri chips become pliable, so as to be easily bent, and are then wetted with water if in large quantity or with sputum if in small, and teased up with the fingers so as to remove all the bigger pieces. Some leaves of a certain species of ‘wattle’ … or of gidyea7 when the former is not obtainable, are next heated over the fire and then burnt, the ashes being retained. The pituri in its moist state is now mixed with these ashes on 7 The wattle and gidyea referred to have been identified respectively as Acacia hakeoides and A. omalophylla.

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some smooth surface, a ‘pituri-plate’, koolamon &c., and worked with the fingers into small rolls about 2½ inches long by 5/8 inches diameter, which ‘quids’ are now ready for chewing. Sometimes, the quid is teased up with some shreds of native flax [Psoralea] to give it compactness and intercoherence. When not being chewed, these rolls are carried worn above and behind the ear … At Quarmby, I learn that the Kalkadoon will often prepare their tobacco in similar manner to the pituri, which is made into a quid with certain gidyea leaf ashes for chewing. Amongst the aboriginals themselves everywhere as great a craving appears to exist for pituri as alcohol for Europeans, a fact which is put into practical and economic effect by drovers, station managers, and others.

Pituri plant in the Simpson Desert, and track across the desert plains. (Information Annie Hansen; images courtesy Iain Davidson, flickr)

The Problem of Identification

The botanical classification of the mysterious narcotic was beset by difficulty and delay. Identification of the source of a crushed, powdered or masticated piece of leaf material was bound to be problematic unless specimens of the wild plant were available. As the substance was widely traded across the country, access to the original plant source was not an easy proposition. The raw drug that was carried the long distances for barter was merely a mass of twigs and crushed leaves. Wills’ diary entry of 7 May 1861, quoted previously, included the following description: ‘The pituri consists of leaves broken into small particles and mixed with acacia leaves, small dried berries containing reniform seeds [pituri seeds] and unexpanded flower buds of the shape of a minute caper’. Unsurprisingly, Aboriginal people were unwilling to part with any information regarding the herb. This made the quest for the plant’s origin even more difficult. A Mr Wiltshire provided Bancroft with details of the problem: For many years I have by hearsay been acquainted with the properties of pituri. In South Australia, in the neighbourhood of Lake Hope, the natives procure it from other natives making their annual visit South for the red ochre so valued by them. On questioning the visiting natives, who have all the marks of long travel, as to where pituri grows, I found them wonderfully reticent, the only answer I received being an indication by a motion of the hand in a Northerly direction and a rattling noise made in the throat intended to signify that it was a long way from there. It is much sought after by the natives, who will give anything they possess for it – not for the

purpose of exciting their courage or of working them up to fighting pitch, but to produce a voluptuous dreamy sensation. I have heard of pituri producing a fierce excitement, but I have never seen it, as far North as I have been. It may be that there are other plants that will produce the latter effect, but I have never seen or heard of them. Going into the interior from the coast … you will meet natives whose ‘possible sacks’ or ‘dilly bags’ contain frequently pituri or something very like it. On making them understand that you wish to know where it grows, they will point southwards and say ‘tirr-r-r-r-r’, meaning a long way. This, I am inclined to think, is the same plant as is used by their countrymen in the south (Bancroft 1885).

Many years were to pass before its origins were revealed with any certainty. Another report by Mr Sylvester Brown detailed the collection of the herb: The blacks break off the pituri boughs and tie them up in netting till dry; then when thoroughly dry they break the leaves up and enclose them in closely netted bags in the shape of a crescent. These are easily carried for the purpose of barter, which is carried on as far as Cooper’s Creek and the Barcoo. Before chewing they burn the

PITURI: A MYSTERIOUS NARCOTIC leaves of a shrub they call ‘montera’, and moistening the ashes mix and chew. I have not noticed any abnormal result from the habit, though I have heard that a black unaccustomed to the weed becomes intoxicated thereby (quoted in Bancroft 1885).

Joseph Maiden (1889) gave an interesting description of the effects of the stimulant, which had a decidedly expedient role in Aboriginal culture, particularly when travelling: ‘It is also smoked, and to prepare the leaves for this purpose they are damped, mixed with potash prepared from the ashes of suitable plants and rolled up in the shape of a cigar. This is often chewed and the saliva swallowed. In small quantities it has a powerful stimulating effect, assuaging hunger, and enabling long journeys to be made without fatigue, and with but little food. It is also used by the aboriginals to excite them before fighting.’ A Western Australian account also made a particularly interesting observation of the use of the smoke, inhaled from burning pituri leaves, as an anaesthetic for such ‘operations as they performed’ (Herbert 1926). To complicate manners the use of the word ‘pituri’ itself was debatable. Originally it was used only by Aboriginal people on the Upper Mulligan River, in southeastern Queensland; other tribal languages had different names for it. Eventually the term ‘pituri’ entered into general use throughout the country. This caused great confusion, because it was also widely adopted to describe the many forms of native chewing tobacco – including that originating from species of Nicotiana. The term could even be applied to associated plants, such as the Acacia ash utilised as an additive. George Aiston (1937) provided clarification: ‘a great trouble to investigators is the lack of words in the aboriginal language; the one word pitcheri had to deal with the whole subject; the bush, Acacia salicina, in this country (Lake Eyre district) was more often known as pitcheri than by its native name wirra. The ashes resulting from burning wirra bush tips were always known as pitcheri. So that any one asking would be shown perhaps half a dozen trees which would all be quite truly called pitcheri, although they only supplied supplementaries to the real substance.’ Pituri’s true identity was further obscured by the fact that the plant had a reputation as waterhole poison in some parts of the country for capturing game such as emu and kangaroo.

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The Poison Puzzle

Camels were used for personal transport in the outback. (Lantern slide used by Rev. FH Paterson, South Australia, 1870s–1930s.) (nla.pic-an24165494-v)

Camels were the main beasts of burden for many outback expeditions in the 1800s and 1900s. They were used by Burke and Wills (1860), the Elder Expedition (1891–92), the Horn Scientific Expedition (1894), the Calvert Expedition (1896–97) and the Madigan Simpson Desert Expedition (1939). Pastors, postmen, pastoralists, transport and medical services also utilised the services of these animals on a regular basis. Early reports mention that camels, as well as sheep and cattle, had died after eating the leaves of Pituri. Camels were said to be particularly susceptible to the effects of the plant and ‘succumb if they eat only one mouthful of the bush torn off during a journey’ (Stanton Hicks & Le Messurier 1935). Detailed observations were recorded in notes dated 10 June 1901, by Richard Helms, the botanist accompanying the Elder Expedition. In a letter to Joseph Maiden, he commented: Glancing through your list of ‘Poison Plants of Australia’ in the Agricultural Gazette for this month, I notice the omission of Duboisia Hopwoodii. It is certainly poisonous to camels, and, therefore, probably also to other animals. Camels rarely feed on the ground, and where Nicotiana suaveolens grow to a height of 4 to 6 feet, as at the Everard

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Camel train. (Image from Australian Inland Mission collection, Head Office, 1926–1940.) (nla.pican24134642-v) and Blyth Ranges, these animals eschewed this plant. I cannot, therefore, believe that they should have picked the scantily occurring dwarf specimens later on, when several severe cases of illness occurred amongst the caravan. However, young succulent shrubs of D. Hopwoodii, whenever these almost disastrous events occurred, were always met with. For these reasons I attributed the severe attacks of several camels occurring within a few weeks to D. Hopwoodii, and I am convinced that a very small quantity is sufficient to bring about serious results. None of the camels I observed died, but they staggered for several days, after recovering from the severe paroxysms, and were useless for upwards of a week.

These reports were puzzling in the extreme. It was highly unlikely that the Pituri chewing ‘tobacco’ could be a potent poison. It simply did not make any sense. Professor Geoffrey Blainey commented: ‘Similar drugs [Duboisia species] were widely used for hunting and fishing in central Australia. The placing of twigs of Duboisia in a waterhole poisoned the water; emus which drank it were stupefied and easily caught. Another variety of the Duboisia [D. leichhardtii] was used along the Shoalhaven River, near the coast of New South Wales. A branch soaked in a pool so affected the water that eels were intoxicated and easily caught’ (Blainey 1977). In northern Queensland, however, Walter Roth noted that: ‘pituri is certainly never used in any of these districts for contaminating the water holes with the object of drugging the birds and animals drinking therein’ (Roth 1867).

‘Emu Sneaking’ from Australian Sketch Book, by S. T. G. (25 coloured plates of Australian Gold Rush 1850–1860). (nla.pic-an7149202b-v)

Spencer and Gillen (1899) observed in Central Australia that the: ‘leaves of the Pituri plant (Duboisia Hopwoodii) are used to stupefy the emu. The plan … is to make a decoction in some small waterhole at which the animal is accustomed to drink. After drinking the water the bird become stupefied and easily falls prey to the … spear’. Similar observations were made by Pastor Schulze, a German missionary at the Finke River Mission (1891). (Image courtesy US Army, 2009)

A Desert Poison?

The Codonocarpus genus is very small – containing only three native species: C. attenuatus (Queensland, NSW), C. pyramidalis (South Australia, NSW), and the Desert Poplar (C. cotinifolius). The latter, which is the most abundant, is found throughout the desert regions, ranging from the east to the west coast. It has an important environmental role, albeit a


Codonocarpus attenuatus. (Images courtesy John Forlonge, flickr)

short-lived species. The tree (lower trunk and roots) can support large populations of small edible grubs (beetle larvae) that have been an important part of traditional diets. The waterretentive leaves provide shade and have even been used as a lining for large earthen resting holes during scorching hot days (Latz 1996). Codonocarpus cotinifolius was also known as the Quinine Tree or Medicine Tree of the interior: ‘This bark, which is exceedingly brittle, and by no means thick, contains a peculiar bitter, and no doubt possesses medicinal properties. The taste is, however,

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Codonocarpus cotinifolius. (Courtesy Keith AW Williams, Native Plants of Queensland, Vol. 2)

distinct from Quinine’ (Maiden 1888). The bitter quality of many herbs (which was characteristic of alkaloid components) was commonly associated with presumed medicinal potential – particularly as Cinchona bark and quinine were so intensely bitter that few would willingly tolerate the medicine unless there was great need. In Western Australia, Desert Poplar leaves were used as an analgesic. They could be chewed to treat toothache, while a root bark infusion (prepared with Acacia cuthbertsonii) provided a liquid in which limbs afflicted with rheumatic pain were immersed. The roots were also reputed to have been chewed as a narcotic (Reid & Betts 1979). In the Northern Territory a decoction prepared from the crushed leaves was applied as an analgesic body wash to ease chronic internal pain and feverish conditions, including influenza. Sometimes the leaves were simply crushed and rubbed over the affected area (painful joints, the chest or abdomen) or applied as a poultice. The softened root bark was similarly utilised for the relief of joint pain (Barr 1988). Furthermore, an infusion of the Desert Poplar with Prickly Fanflower (Scaevola spinescens) leaf and twigs provided a cancer remedy – although ‘later work on this cure was inconclusive’ (Lassak & McCarthy 1992).

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Joseph Maiden provided details of the aromatic attributes of the shrub – which were compared to the mustard-like character of Horseradish (Armoracia rusticana): ‘Its leaves resemble horseradish, or turnips in taste. The bark is smooth, and when quite fresh of a pinkish colour’. He commented that the allied species Codonocarpus australis had a distinctive aromatic quality: ‘While dissecting the flowers and fruit, they were found to diffuse a most powerful smell, resembling that of ether’ (Maiden 1900). Benzyl cyanide and a sulphur-containing glycoside (cochlearin) have since been isolated from the volatile leaf oil. Alkaloids may also be present (Lassak & McCarthy 1992). Professor Len Webb mentioned the tree’s use as a poison – the leaves and branches were crushed and put in drinking water to kill dogs and game animals – the game was eaten only after the stomach and intestines were removed. It was also considered poisonous to humans (Webb 1969a). However, Peter Latz comments: ‘Desert poplar is however eaten by camels and other animals with no ill effects; probably there is some confusion between this plant and the closely related shrub Gyrostemon which is sometimes used for this purpose [poisoning game]’ (Latz 1996). The Gyrostemon genus belongs in the same family as Codonocarpus, the Gyrostemonaceae.8 Gyrostemon ramulosus is a shrubby fire-tolerant shrub of inland Australia with fruits similar to those of Codonocarpus, albeit smaller in size. Selwyn Everist noted that this species was called ‘Camel Poison’: ‘Giles (1889) reported that during the course of his Exploring Expeditions in 1875 and 1876, two camels died and many others were unable to move after eating this plant. Stomachs of the dead camels contained chewed-up fragments of this plant’ (Everist 1981). Gyrostemon tepperi (syns G. australasicus, Didymotheca cupressiformis), has also been known 8 Overall there are only 22 native species in the Gyrostemonaceae family (which contains 5 genera), with the largest proportion (16 species) placed in Gyrostemon – all of them endemic to Australia. A number of Gyrostemon species were formerly classified as Didymotheca and Cyclotheca. Codonocarpus cotinifolius was also once placed in Gyrostemon.

as ‘Camel Poison’, and has occasionally been used as a substitute for Duboisia for catching game at waterholes (Latz 1996). Everist mentions that Gyrostemon australasicus has been suspected of poisoning horses.

Gyrostemon ramulosum, from Pierre Jean Francois Turpin, Dictionnaire des Sciences naturelles (1816–1829), FG Levrault, Paris & Strasbourg.

In general Aboriginal people did not encourage the indiscriminate use of plant-derived poisons, including ‘pituri’, in waterholes because of the contamination risk. The practice was usually limited, where possible, to a section of a waterhole (the site dammed off) or to a smaller site within a series of waterholes. Those


areas treated with a toxin were signposted as such. There are, however, conflicting reports from Central Australia that mention the water was drinkable – albeit not immediately, but a few days after Pituri had been employed (Latz 1995). This could possibly mean that the water source was fed by a stream or spring which cleared out the pool – or it could be due to a variation in the toxicity of the local plant resources. Even so, it seemed extremely unlikely that a highly effective animal poison could be used as a narcotic. This form of pituri was not traded and rarely used for poisoning purposes outside Duboisia’s natural distribution, which suggested there could be an anomaly in plant identification. Part of the explanation was to lie with the use of other plants in many regions of Central and Western Australia, particularly the ‘Native Tobacco’ pituri (Nicotiana spp.). Information regarding Duboisia’s chemical and species variability was to later provide the rest of the solution. Duboisia myoporoides, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1887.

Aboriginal fishermen with spears on the Upper Roper River, Mataranka, Northern Territory. (Frank Hurley collection, 1910–1962.) (nla.pic.an23504709-v)

The Genus Duboisia

Duboisia is a very small endemic Australian genus that contains only four species, two of which are fairly widespread: Duboisia hopwoodii of the inland deserts, and the Corkwood, D. myoporoides, of Queensland and northern New South Wales. The discovery of the genus in 1802 was based on Duboisia myoporoides, which is also native to

Duboisia myoporoides fruit. (Courtesy John Moss Wikimedia Commons, Public Domain)

New Caledonia. Duboisia hopwoodii and D. leichhardtii were not botanically identified until the 1860s.

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Duboisia myoporoides was named in 1810 by the celebrated botanist Robert Brown and said to commemorate Louis Dubois 9 , the French author of a work on the botany of Orleans, published in 1803. The species name myoporoides, of Greek origin, refers to its resemblance to the coastal tree Myoporum acuminatum (Maiden 1893). The Leichhardt Corkwood (Duboisia leichhardtii), which has a restricted distribution to the west of Brisbane, was originally described from a sample collected by Ludwig Leichhardt. It was named in his honour by von Mueller in 1877. Duboisia hopwoodii is widespread throughout the desert and outback regions (Western Australia, central Australia, western Queensland and New South Wales). Its name commemorated Henry Hopwood, the sponsor of the Burke and Wills ‘Victorian Exploring Expedition’ – which was to explore the continent from north to south, crossing a massive distance of over 3,250 kilometres (2,000 miles) from Melbourne to the Gulf of Carpentaria on the far northern coastline. One other Duboisia species has been described only relatively recently, in 1995. Duboisia arenitensis has a highly restricted distribution at Mount Gilruth, west Arnhem Land, Northern Territory. It has characteristics similar to Duboisia myoporoides and D. hopwoodii, while D. leichhardtii is more botanically distinct. Another species, initially named Duboisia campbellii, was later classified as Eremophila saligna.

9 Brown was a distinguished Scottish naturalist who wrote a remarkable review of the botany of New Holland (1802–05) after he had accompanied the Matthew Flinders expedition that circumnavigated the Australian continent. Paul Foley (2006) mentions that the name Duboisia could also refer to Charles Du Bois, treasurer of the East India Company (1702–37), who had a botanical garden at Mitcham in Surrey.

Duboisia myoporoides in flower. This species was thought to have a Myoporum-like appearance. (Courtesy Brian Myers)

Mangrove or Pointed Boobialla, Waterbush (Myoporum acuminatum) is a coastal species that favours rainforest, Eucalypt forest or the margins of mangroves. (Courtesy Peter Woodard)

Ultimately the Pituri Bush, Duboisia hopwoodii, was identified from the arid regions of Central Australia and Western Australia. This is an extremely firetolerant shrub that favours sandy spinifex habitats (Latz 1995). Professor Geoffrey Blainey (1977)


provided some interesting details regarding the botany of the tree, and the notoriety of its namesake: The most common species of native tobacco was Duboisia hopwoodii, named by the botanist Baron von Mueller after Henry Hopwood, a former convict who, in 1856, built a pontoon bridge across the Murray at Echuca. It was perhaps appropriate that Australia’s most famous narcotic should have been named after an ex-convict. One celebrated species of pituri came from south-western Queensland, especially around the Upper Mulligan River. The shrub, a species of Duboisia, was a twiggy wheatenyellow plant which a white man, craving for tobacco, would have walked past without realising its punch. By what accident or experiments its narcotic qualities were discovered by aboriginals will never be known, but it was one of the hundreds of useful botanical discoveries whose utilitarian value surpassed those made by outstanding European botanists in Australia. The plant flowered about August, and the flowers and thin leaves and dry stems were harvested and dried. They were carried in netted bags about the size of a women’s small handbag. The mixture consisted mostly of yellow twigs, not unlike the ‘wood’ one sometimes finds in a packet of coarse ready-rubbed tobacco.

Pituri bushes in the desert. (Images courtesy Andrew Harper, Australian Desert Expeditions)

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Even in those early days, Pituri’s potential was readily apparent to the colony’s scientific community – although the fact that it was to later achieve the status of an invaluable drug resource was quite unexpected. Dr Joseph Bancroft undertook extensive chemical evaluation of the plant and recorded details of his search in a paper on Pituri and Tobacco: In March of 1872 I had the honour of reading before this Society an account of the first experiments made with the Pituri of our aborigines. I was so startled by the toxic energy of the substance that my paper was headed ‘The Pituri Poison’ … For five years afterwards no clue could be found to ascertain what plant produced the Pituri that the Central Australian man held in such high estimation, though Mr. Bailey, our botanist, and Baron von Mueller, were put frequently on the rack by my inquiries and specimens transmitted. The plant, however, which Hodgkinson, the explorer, collected in 1877 were not ground into particles, as is the condition of the Pituri procured from the natives. So, after I had ascertained that these specimens had the same poisonous properties as the native’s Pituri, they were forwarded by Mr. Bailey to Baron von Mueller, who at last was able to clear up the mystery and tell us that the plant was Anthocercis or Duboisia Hopwoodii. The learned Baron’s suggestion for me to examine Duboisia myoporoides led to the discovery of that curious mydriatic now establishing itself as a potent remedy on Ophthalmic practice in Europe (Bancroft 1895).

Logically, closely related species could be considered candidates with equally interesting chemical potential. The first early record of the toxic attributes of the Corkwood Duboisia (Duboisia myoporoides) was made in the 1860s by the Reverend Dr Woolls in A Contribution to the Flora of Australia: ‘[it] probably possesses deleterious properties. I have been informed by Miss Atkinson that the aboriginal natives used to prepare some stupefying liquid from it, and also the branches of the tree, when hung up in a close room, had the effect of producing giddiness and vomiting in delicate persons’. Its ‘intoxicating property’ was said to be potent: ‘The aborigines make holes in the trunk and put some fluid in them, which, when drunk on the following morning, produces stupor’ (quoted in Maiden 1889). It is possible that reports of the use of the sap of Corkwood Duboisia as an intoxicant or hunting poison were misleading. Only one medicinal use of this plant was later recorded from New Caledonia

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– where the young leaf infusion was employed as a remedy for ciguatera poisoning. In contrast, there was no doubt about the use of Duboisia hopwoodii as an Aboriginal hunting poison (Foley 2006; Bourdy 1992).

Gyrocarpus: Another Tropical

‘Corkwood’

Gyrocarpus americanus has been known by a number of names descriptive of the fruit, bark or aromatic qualities of the timber: Helicopter Tree, Propeller Tree, Twirly-whirly Tree, Corkwood, Shitwood, Stinkwood. (Image courtesy Keith AW Williams, Native Plants of Queensland, Vol. 1).

Gyrocarpus jacquini (syn. G. americanus), from William Roxburgh, Plants of the Coast of Coromandel, Vol. 1, London, 1795.

The Corkwood Duboisia should not be confused with the ‘Corkwood’ Gyrocarpus americanus (Hernandiaceae family), which is found along the Queensland coastline from Brisbane to Cape York, the Northern Territory and Western Australia (north). This species, which is fairly widespread in the world’s tropical regions, has had a fairly interesting medicinal reputation which suggests anti-inflammatory, analgesic, antiparasitic, sedative and antimicrobial properties. Fijian healers used a fluid squeezed from the bark as a tonic for ‘relapsed illness’, while a bark infusion was taken in Tonga to alleviate swelling following childbirth, for stomach-ache, and to treat filariasis (Weiner 1984). Interestingly, studies of the anti-protozoal potential of medicinal plants of Vanuatu determined that leaf extracts possessed significant activity against the sleeping sickness parasite (Trypanosoma brucei) (Bradacs 2010). The bark decoction was noted to have strong purgative effects and was used for treating constipation (also the leaf infusion), dysentery, aching limbs, arthritis and rheumatic pain. The plant was also used for treating bronchial troubles, epilepsy (leaf infusion) and tetanus (plant) (Cambie & Ash 1994). The tree contains diverse alkaloids (see Cambie & Ash 1994), some of which have curare-like activity; for example, magnocurarine (0.6–0.7%) and phaeanthine (0.4–0.6%) from the bark – although a substantially lower level of the latter was present in the leaves (0.03%), and no magnocurarine (McKenzie & Price 1952). In northern Australia, Aboriginal people employed an infusion of the roots and young shoots (mashed, soaked in water) to ease rheumatism. This could also be applied to old cuts (but not fresh wounds), while the powdered charcoal was considered useful for healing fresh cuts and open sores (Reid & Betts 1977). The bark decoction has also been utilised as a cure for ringworm, although it is specified as being unsuitable for internal use (Barr 1993). In Tonga a similar preparation was applied to skin inflammations (Whistler 1992).


Discovery of a Mydriatic – and Intoxicant

In the 1870s intensive research was undertaken into the pharmacology of Duboisia myoporoides (Corkwood Duboisia). For evaluation purposes, samples from the coastal regions of New South Wales and Queensland had the advantage of being more accessible than the inland Pituri (Duboisia hopwoodii). By October 1877 Dr Bancroft’s experiments with a refined extract left no doubt regarding the herb’s potency. Clinical trials in ‘ophthalmic cases’ soon followed. Bancroft noted that it had: ‘[an] action of great rapidity. A very slight irritation is mentioned by the patient after a drop is placed in the eye, but this passes away in a few seconds. In from five to fifteen minutes an ophthalmoscopic examination can be made … I use the Duboisia now regularly in place of Atropia, and in several extraction cases found it to act satisfactorily.’

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Glycerine Extract of Belladonna (centre), manufactured by Taylors Elliotts and Australian Drug Pty Ltd, Brisbane. (Image from Herberton Historical Village, Atherton Tablelands, north Queensland)

The Infamous ‘Deadly Nightshade’

Extract of Belladonna from British Pharmacopoeia 1867. Juice of Belladonna was noted in the additions of 1874.

Belladonna, from John Lindley, Medical and Economical Botany. Bradbury & Evans, London, 1849.

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Atropa belladonna in cultivation at Chelsea Botanic Gardens, London.

Belladonna (Atropa belladonna), Henbane (Hyoscyamus niger) and Stramonium (Datura stramonium) primarily contain atropine and hyoscyamine. The clinical value of atropine lies in its antispasmodic properties, which are particularly useful for the treatment of gastrointestinal spasm (gastritis, enteritis, hyperacidity) and asthma – as well as arrhythmia due to bradycardia (slow heartbeat). Unfortunately, early attempts to grow Belladonna in Australia gave only a low alkaloid yield and the labour costs were high. Later efforts with regard to developing crops of Henbane and Datura were equally disappointing due to damage from insect attack and viral disease (Foley 2006). The word Belladonna means beautiful (bella), lady (donna) – in reference to an old use of Atropa belladonna juice as a cosmetic. It was dropped into the eye to dilate the pupil, whereby the lady supposedly acquired a ‘striking appearance’. In the nineteenth century

ophthalmologists put the mydriatic properties of Belladonna (plant extracts) to a more practical use by utilising the drops to dilate the pupil to facilitate eye examinations. However, the incautious use of the medication could have devastating side effects. Physicians were well aware of the complications associated with the use of the drug, as Sir John Herbert Parsons noted in Diseases of the Eye (1927): ‘Atropin [sic], which is always resorted to by the inexperienced in intractable diseases of the eye, does much more harm than good. It causes great inconvenience from paralysis of accommodation and has little effect upon the conjunctiva, such as it has being deleterious. Apart from this, it is extremely dangerous in elderly patients, who are specially liable to chronic conjunctivitis. In them, more than in others, there is grave danger that atropin may induce an acute attack of glaucoma, a disaster which it is impossible to overrate.’ In the 1860s the eminent London pharmacist, Peter Squires, introduced the use of an atropine liniment preparation for the relief of nerve pain. Similar recommendations were common in folk medicine where the herb was popularly applied to skin tumours and other painful conditions – albeit it possesses a limited local analgesic action. Moreover, Belladonna was known to have a potent antispasmodic effect that was responsible for its traditional reputation as an effective remedy for gastrointestinal or urinary tract spasm. The herb was traditionally recommended in a range of conditions such as peptic ulcers, ulcerative colitis and painful griping diarrhoea. In 1881 George A Gibson wrote a paper on the action of Duboisia on the circulation which was read before the International Medical Congress in August of that year: ‘The alkaloid Duboisia dilates the pupil, dries the mouth, quickens the pulse, arrests perspiration, produces headache, causes drowsiness, and finally induces tetanus after the lapse of some hours from the time of administration. As might be expected, it acts as an antagonist to muscarine as well as to pilocarpine.


Pilocarpine, from The Merck Index, 5th edition, 1940. Pilocarpine was extracted from the tropical American shrubs of the genus Pilocarpus, notably P. jaborandi, in 1875. This drug was used for the treatment of glaucoma for over a century because it improved the fluid drainage from the front chamber of the eye, and its rather remarkable effects quickly made it an extremely valuable medicine. JF Bailey commented in the Queensland Agricultural Journal of 1898 that: ‘True Jaborandi is a powerful sudorific [diaphoretic or sweat-inducing agent] and sialagogue [salivary stimulant]; after a time a large dose acts as an emetic, contracts the pupil of the eye, and causes the approximation of vision. It has been used in a great variety of diseases, most successfully in asthma, diabetes, and as an antidote to belladonna poisoning. It causes diarrhoea, and promotes secretion of milk. It is also employed as a hair wash.’

It thus appears that Duboisia has on the whole a series of actions very similar to those of Atropia, and the physiological effects of the alkaloid seem, therefore, to lend a powerful support to the botanical reasons for the classification of the plant along with the Solanaceae.’ Additional side-effects included delirium, lethargy,

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stupor, limb twitching and visual hallucinations. Some individuals were intolerant of the drug, even when it was applied locally to the eye as a mydriatic. The acute systemic toxicity could be ameliorated by the administration of coffee or lemon juice. These symptoms closely resembled Belladonna intoxication. They were worse with injectable formulations because the drug had cumulative effects. Certainly it was well known that atropine had powerful pharmacological properties and its use was not without risk. As with most of the tropane alkaloids the drug is not amenable to casual experimentation, particularly as a hallucinogenic agent. Mental symptoms (excitement, agitation, drowsiness, confusion) can result from even small doses in susceptible individuals. Its use can easily provoke a familiar triage of symptoms colloquially described as ‘blind as a bat, mad as a hatter (or crazy as a loon), red as beet (beetroot), hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone’. This is highly descriptive of the symptoms: hot dry skin, flushing, cardiovascular distress (arrhythmia, palpitations, tachycardia or hypotension), hallucinations and inhibition of secretions (including sweating) – with a resultant dryness of the mucous membranes affecting the mouth, skin, stomach and bronchi. In addition, urine retention (inhibition of bladder control) can occur, and decreased intestinal and gastric function (constipation, increased gastric reflux). Severe cases are associated with central nervous system depression, circulatory collapse, coma, muscle paralysis, and death due to respiratory failure.

Mistaken Identification

Bilberry (Vaccinium myrtillus).

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It is no surprise that Belladonna has long been associated with incidents of accidental poisoning. Inadvertent experiments, such as those resulting from mistaken identification, can be highly hazardous. In 2000 in East Sussex, England, Belladonna berries were mistakenly used to make a Bilberry pie. Those partaking quickly succumbed to atropine poisoning. Another case in Switzerland recorded the accidental impaction of a wood splinter in the eye. Belladonna wood contains substantial amounts of alkaloids (possibly even more than the berries) and the resultant mydriasis was not unexpected (Berney & Wolfenberger 2000; Southgate 2000). More recently a similar incident was recorded when Belladonna fruit (which are black) were mistaken for ‘blueberries’ – with a similar toxicological result (Mateo Montoya 2009). Physostigmine can be used to antidote atropine poisoning, usually in combination with sedatives to treat the delirium and mental confusion.

Duboisine or Atropine? The Commercial Market

Duboisia leaves.

Investigations ultimately led to the extraction of an alkaloid-based substance named ‘duboisine’ – the early supply of which was a relatively expensive undertaking. The fact that it had little advantage over atropine, a substantially cheaper product, limited its commercial value. A trade report of May 1891, issued by Gehe and Co. of Dresden, noted: ‘Though certainly not quite at a standstill, the employment of duboisine is decreasing. Considering the high price of the compound, necessitated by the expensiveness of the raw material, this is not surprising, particularly in ophthalmology; it does not possess the slightest advantage over atropine sulphate.’ The Merck Index for 1889 quoted the price of duboisine (a pure crystallised alkaloid) at 16 shillings 8 pence per 15 grain tube. The price of the amorphous sulphate was 7 shillings 6 pence for the same quantity. Joseph Maiden commented: ‘While these prices are high and almost prohibitory, I do not say they are excessive, considering the difficulties importers have had to contend with in getting supplies of the raw material. While the raw material is plentiful enough in some districts, it is not inexhaustible.’ However, even at this early stage, Maiden expressed concerns regarding the indiscriminate and destructive harvesting methods that were being employed: ‘collectors of the leaves should never cut down the trees, but prune the limbs or twigs, an operation which will be advantageous to the tree rather than the reverse. Chopping down the trees unnecessarily is killing the goose with the golden eggs, and such conduct will bring its own punishment.’ This advice often fell on deaf ears. Maiden elaborated on other useful characteristics of the drug: ‘In practice the sulphate of the alkaloid, which forms golden-yellow scales, is usually preferred. The dose is from 1/120 to 1/30 of a grain. The extract is said to have been given with great benefit in cases of the night sweats of phthisis [a wasting disease, generally associated with tuberculosis], without producing any bad effects on the appetite. It produced entire relief from pain in a severe case of vesical tenesmus [painful spasm] from inflammation of the urethra and neck of the bladder.’ It was also employed for goitre and as a sedative for mental disorders (‘to dispel maniacal delirium’; Morton 1977). The ointment was found useful for local application as a sedative in cases of corneal inflammation of the eye (keratitis) (Maiden


1889). In ophthalmology, the drug was also utilised for treating nearsightedness, accommodation spasm of the eye, and temporary paralysis of the ciliary muscles. Some authors commented that the mydriatic effect of duboisine worked within 6–8 minutes, while that of atropine was later (14–15 minutes). The duration of duboisine’s effects was also said to be longer (Foley 2006). As early as 1919, the American herbalist Dr Finley Ellingwood provided a good overview of the medicinal reputation of the Australian Corkwood. He mentioned two preparations of Duboisia myoporoides: Extract of Duboisia, and Fluid Extract of Duboisia – about which he commented:

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The agent has not been extensively used for internal administration. It soothes the respiratory apparatus, increases the action of the heart, like belladonna in congestions, and is given to control excessive night sweats. It has been given in some cases of maniacal excitement, but it must be given in the enfeebled cases and not when there is fullness— engorgement of the circulation of the cerebral organs. It has been used in the treatment of emotional insanity and delirium with excitement. Duboisine is given in doses of from 1/120 to the 1/60 of a grain in these cases, and is said to be a valuable hypnotic. In a few insane patients, especially those with hysterical manifestations, it has caused regurgitation of the food. It is also used in muscular tremblings, paralysis agitans10, and epilepsy. There are a few patients who are especially susceptible to its use and will experience vertigo, fullness of the head, a feeling of danger and heart pains, even from small doses, or from a single drop of a one per cent solution in the eye.

While the use of duboisine as a sedative and hypnotic for treating mental disorders was not widespread, European psychiatric sanitoriums, particularly in Germany and France, continued to employ the drug as a sedative until the outbreak of World War II. 10 Paralysis agitans is a synonym for Parkinson’s disease, a degenerative neurological disorder characterised by problems with muscular coordination and tremors.

Tropane Alkaloid Mydriatics

‘An Australian Medicinal Leaf ’, The Star, 22 May 1895, Christchurch, New Zealand.

Within the tropane alkaloid classification, atropine does not have the strongest mydriatic activity – that claim belongs to hyoscyamine, with atropine being next in potency and scopolamine the least active. However, atropine was more suitable for development as a mydriatic because it was easier to standardise than hyoscyamine and, in the small doses needed for ophthalmic examinations, did not result in side-effects that affected the central nervous system (Grynkiewicz & Gadzikowska 2008). Even so, when using herbal preparations, as opposed to a purified alkaloid, the effects of other modifying components come into play. There is also the problem of chemical variation between samples. This means that, despite the reliable mydriatic activity of the preparation,

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there could be differences in the activity of products like Belladonna or the Corkwood herb. With reference to the use of Duboisia extracts, Finley Ellingwood (1919) commented: ‘It has no properties not possessed by atropine, although it is claimed to produce its effects in paralyzing accommodation and dilating the pupil more rapidly, with less conjunctival irritation and with more speedy recovery. The hypodermic injection of duboisine will antagonize the influence of opium or morphine as effectually as atropine.’

The initial success with Duboisia as a mydriatic, inspired by the work of Joseph Bancroft, led to the export of the drug (dried leaves), although it was difficult to procure in any quantity. At the end of the nineteenth century there was certainly a good market in the raw material, details of which Joseph Maiden recorded: The leaves form the most valuable part of the tree. They are carefully dried in the shade, and when they have been deprived of as much moisture as possible, they are packed in sacks or boxes, care being taken not to break up the leaves unnecessarily. The market for them is chiefly in Germany, and the price varies according to quality and the state of the market, from about 4d. [pence] to 1s. [shilling] a pound, packed for shipment. It is not yet known what the extent of the demand for this drug is, mainly, I believe, because of the difficulty which manufacturers in Europe have had in procuring regular shipments of uniform quality … Just a word of warning. The leaves are poisonous (though not violently so), but accidents from them are very rare (Maiden 1893).

It was not until the early 1900s that further serious efforts were made to unravel the chemistry of the plant.

Alkaloid Conundrums

Many surprises regarding the chemical variability of the genus Duboisia were to follow. Professor EH Rennie (1926) provided greater detail:

Atropine, from Peter Squires, Companion to the Latest Edition of the British Pharmacopoeia, London, 1899

Coming now to the consideration of other poisonous substances chiefly alkaloids, it may be noted that they frequently occur in groups, the members of which are often, but not always, closely related both in chemical and physiological properties as, for example, in cinchona bark, which contains several alkaloids similar to quinine. In such cases complete identification is often rendered uncertain owing to difficulties in separating the constituents from one another and obtaining them in a pure state. One outstanding example is to be found in the case of the poisonous principles associated with the genus Duboisia … Pituri was examined by Prof. Liversidge many years ago and he extracted from the leaves an alkaloid resembling nicotine, but not, in his opinion at the time, identical with it. Later it was proved by Petit of Paris, and Rothera, of Melbourne, to be really nicotine. The poisonous principle in D. myoporoides was obtained in the form of an extract and examined by several chemists and physiologists. It was recognised as possessing alkaloidal properties and was called Duboisine, and the name is still


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to be found in some drug price lists. As late as 1916 the ‘pure crystalline sulphate’ was quoted in Britain at 25 pounds per ounce. Its importance consists in the fact that it is a powerful mydriatic and has been used for that purpose.

For many decades hyoscine-based preparations remained clinically important for the investigation of eye disorders. For this reason, nearly seventy years after the experiments of Joseph Bancroft, Duboisia would continue to be recognised in official pharmacopoeias. Duboisine continued to be included in the Martindale Extra Pharmacopoeia up until the 25th edition (1967) albeit, by then, rarely employed in clinical practice. It was omitted from the following edition (1972) – although Duboisia myoporoides continued to be listed as a source of hyoscyamine. Homoeopathic texts still list Duboisia and Duboisia Sulphate for treating eye disorders such as conjunctivitis, mydriasis, eye pain and a specific form of vision impairment associated with a ‘red spot’. It is also utilised in neurological problems associated with trembling, numbness and weakness. Eventually, duboisine was determined to be a mixture of compounds. Professor Rennie’s discussion explained the problems that were encountered:

Duboisia myoporoides. (Courtesy Brian Myers)

Duboisia myoporoides and Duboisine Sulphate, from the British Pharmacopoeia, 1867. The chemists who first examined it [duboisine] differed as to its identity, some supposing it to be hyoscyamine, and some scopolamine. After detailed investigation of the carefully purified material, Petrie has come to the conclusion that ‘Duboisine’ is really a mixture of at least 3 alkaloids, hyoscyamine, norhyoscyamine and scopolamine. Such are the complications met with in this class of compounds, the difficulty of dealing with is much increased by the small quantities present. Following a method of fractional crystallisation … used in the treatment of the extract of Scopolia japonica, Petrie has followed up his work by a very careful investigation of the alkaloids of Duboisia leichhardtii and has identified 5 individuals viz. hyoscyamine, norhyoscyamine, scopolamine and small quantities of atropine and noratropine. The two species of Duboisia last referred to resemble one another closely, therefore, in their alkaloidal content, but differ entirely from Duboisia hopwoodii which contains only nicotine. On examination of another of the Solanaceae Solandra longifolia, the same chemist found norhyoscyamine as the chief alkaloid with some hyoscyamine. He also found nicotine in the leaves of Nicotiana suaveolens, the native tobacco of Australia.

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Confusion could easily have resulted from chemical variation in the samples of plant material examined. Some commercial preparations of ‘duboisine’ were principally composed of scopolamine. However, the duboisine first described by Bancroft was primarily hyoscyamine. Even in the 1890s it was known that as many Solanaceous drug-plants age, hyoscyamine levels increase, while scopolamine levels decrease. Preparation methods of the drug would also have contributed to variation in the chemical constituents (Foley 2006).

Ornamental Solanaceae Relatives

Solandra longifolia.

The Solandra genus was named in honour of the Swedish botanist, Daniel Carlsson Solander (1736–82), who was a pupil of Linnaeus. In association with Sir Joseph Banks, Daniel Solander accompanied Captain Cook’s Endeavour voyage in 1770. The Solandra genus contains around a dozen vine-like plants that are native to South America, Cuba and Jamaica, some of which have become widespread ornamentals – among them S. longiflora, S. maxima and S. grandiflora. These rainforest lianas can develop into massive, thick ropy vines that naturally seek the canopy heights. They have serious invasive potential making them an undesirable addition to the native rainforest. Solandra vines contain atropine and/or hyoscyamine (and their nor-derivatives) as their main alkaloids. Solandra longifolia was the first species investigated in 1916 by Petrie.

Solandra maxima. (Courtesy Kim & Forest Starr, Hawaii)

Investigations of other species, such as Solandra grandifolia, S. guttata, S. hartwegii (syn. S. maxima), S. hirsuta and S. macrantha, showed a similar chemical profile, plus various other tropane alkaloids similar to those found in Datura (e.g. littorine). There was, however, an exception: valtropine was present in the roots, an alkaloid more commonly found in the genus Duboisia (Griffin & Lin 2000). These plants are toxic. Near-fatalities have occurred with children sampling the attractive golden globe-like flowers. Idiotic drug experimentation has likewise landed people in hospital. Symptoms of intoxication include dilated pupils, an unsteady gait, excitability, hallucinations and psychosis. Treatment involves measures to counteract atropine poisoning and hospitalisation until the hallucinations and psychosis resolve (which can take a long time). The plant sap is equally toxic. Eye contact can cause dilatation of the pupil and loss of pupillary reflex activity. Even exposure to the fragrance of the flower can result in nausea and dizziness in sensitive individuals (Morton 1982). There are a couple of related Solanaceae genera of chemical interest. Schizanthus, a South American native genus, contains around a dozen species, a number of which are highly attractive ornamentals. Within the Solanaceae they are placed within the Cestroideae, along with the tribe Anthocercideae to which Duboisia belongs. Various Schizanthus species contain tropane alkaloids known as schizanthines – they


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with high levels of nornicotine would have been decidedly undesirable due to the toxic potential of this compound – and these chemovarieties were therefore studiously avoided (Lassak & McCarthy 1992; Watson 1983).

Alkaline Ash Additives

Schizanthus grahamii.

include S. grahamii and S. hookeri (Griffin & Lin 2000). The use of Pituri as a chewing tobacco demonstrated the practical application of some intricate chemical knowledge. Nicotine occurs naturally in plants in a form that is bound to common organic acids. Liberation of the alkaloid from this complex requires the addition of an alkali (such as Acacia ash) – a process that has been commonly used for alkaloid extraction in the pharmaceutical industry. Thus mixing Acacia ash with Pituri enhanced the effects of chewing by promoting the absorption of nicotine through the mucous membranes of the mouth. The alkaloid would not have been readily absorbed otherwise. Nicotine’s potent physiological effects have a particular action on the nervous system. Aboriginal people deliberately selected Pituri resources that contained high levels of nicotine for use as a stimulant. Indeed, the nicotine content of the Pituri crop could be deliberately enhanced by burning off the older branches to encourage the growth of new nicotine-rich shoots. Plants

Acacia salicina. (Courtesy Arran Edmonstone, flickr)

The addition of ash to Duboisia hopwoodii leaves made a particularly potent mix. Professor Len Webb mentioned that a mixture incorporating Acacia salicina leaf ash was smoked to produce ‘drunkenness, drowsiness or dopiness and finally deep and lengthy sleep’. The active ingredient of the mixture, which was called ‘Pithera’ at Woorabinda, Queensland, was thought to be Duboisia hopwoodii (Webb 1969a). Methods of Pituri preparation frequently mention the use of an alkaline admixture that was usually a type of Acacia ash. Professor Liversidge, addressing this topic in 1880, commented: Mr Wilson informs me that the blacks mix the pituri with the ashes of the leaves of a particular plant and usually roll the mixture up with a green leaf into the form of a quid before chewing; the

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addition of the wood ashes is doubtless made for the same reason that lime is mixed with betel by the Malays and others, namely, for the purpose of slowly liberating the alkaloid during the process of mastication. The quid or bolus is, on ceremonial occasions, said to be passed from native to native, each one masticating it for a time, and then passing it on, it finding a resting place behind the original proprietor’s ear until again required … As is the case with other luxuries, it is reserved by the older men for their own use exclusively, neither women nor young men being allowed to use it. The reasons for using it appear to be much the same as those which induce white people to smoke and in certain cases chew tobacco (Liversidge 1880).

The most popular additives were the ash of Acacia stenophylla, A. ligulata, A. murrayana and A. salicina. The latter had a particularly high content of calcium sulphate (around 51%) (Higgin 1903). Additional suitable species include: Acacia aneura, A. calcicola, A. coriacea, A. dictyophleba, A. estrophiolata, A. kempeana, A. minyura, A. pruinocarpa, Allocasuarina decaisneana, Eucalyptus camaldulensis, Eucalyptus coolabah subsp. arida, Goodenia lunata, Grevillea stenobotrya and Grevillea striata (Latz 1996; Peterson 1976).

Acacia hakeoides is a fairly widespread species of the southern part of the continent. It extends from Western Australia (south, around Esperance) and South Australia, to Victoria and New South Wales – and ranges north into southern Queensland. It yields a high quality fuel wood and edible seeds. (Image courtesy Jenny d’Arcy)

Acacia ligulata. (Courtesy Russell Dahms, flickr)

A Native Drug for the War Effort

Grevillea striata. Joseph Maiden noted: ‘Dr. H. Basedow tells me that on the Diamantina River it [Grevillea striata] is the “Ilpara” of the blacks, and that the leaves are burned and the ash added to the leaves of Duboisia Hopwoodii when preparing Pituri’ (Maiden 1924). (Image courtesy Russell Cumming)

Joseph Maiden’s fascination with the Australian flora was to provide him with a great deal of insight in evaluating Duboisia’s early promise. His words, almost twenty years before World War II, were prophetic: ‘Even if, like Alstonia constricta, the crude drug does not realise all the hopes which the ophthalmic surgeon had placed on it, we have the satisfaction of knowing that to the organic chemist it has proved of the highest scientific interest and it is not likely that even yet we have come to the end of our knowledge in regard to it’. Nonetheless, over time, interest in Pituri and the Corkwoods lapsed and the popularity of duboisine as a mydriatic declined. It was, therefore, a bit of a surprise when a more enduring role for this tree was heralded in during the 1940s. World War II was to provide a rather urgent impetus to the quest for alternative sources of essential drugs.


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A Corky Characteristic

(Left) Cork Oak (Quercus suber), distribution: southwest Europe, northwest Africa, growing at Chelsea Botanic Gardens, London; (right) Cork Oak in southern Spain, showing harvested lower trunk section. (Image on right courtesy Bob Cory, Wikimedia Commons)

The true Cork Oak (Quercus suber) has a deeply furrowed lightweight bark from which cork has traditionally been sourced. This corky characteristic is also evident in a number of Australian trees. The Duboisia Corkwoods are one example, as are the rainforest Alstonia (Milkwoods) and the Pink-flowered Evodia (Melicope elleryana) – the latter also being called Corkwood or Doughwood. The name Corkwood was applied to Duboisia myoporoides due to the tree’s distinctive soft corky bark, as Maiden commented: ‘This plant is called Cork-tree as well as Corkwood, on account of its bark, and perhaps also of the lightness of the wood. It must not be confused with other indigenous so-called cork-trees or cork-woods, such as Endiandra Sieberi and Ackama Muelleri [Caldcluvia paniculosa] of the coast districts. It is also occasionally called Elm, though the name is not appropriate.’ The Leichhardt Corkwood refers to Duboisia leichhardtii. Interestingly, the first export of the timber overseas was a Corkwood Duboisia log, harvested from the Illawarra region of New South Wales, which was sent by William Macarthur to Paris in 1855. It was among 350 samples of native timbers displayed at the World Exhibition. All were accompanied by botanical

Alstonia actinophylla, distribution: tropical northern Australia.

specimens which resulted in a correction of identification – the log had been mistakenly labelled Santalum obtusifolium. The description read: ‘A low-branching small tree, with rough, cork-like bark; the wood very white, close and soft, but firm; excellent for wood-carving, and not without beauty for inlaying and cabinet work’. (Maiden 1893). There was no mention of any use of the leaves: ‘Sir William Macarthur was a cyclopaedia of knowledge in regard to the

Alstonia scholaris, distribution: primarily the north–central Queensland coast, also in tropics of the Northern Territory and Western Australia; also India, Southeast Asia, southern China, Malesia and the Solomon Islands.

Melicope elleryana, distribution: the northern tropics, predominantly Queensland and the Northern Territory, ranging along the east coast into northern New South Wales.

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uses to which the blacks put the indigenous vegetation, so that the omission of any allusion to the properties of the leaves shows that he was most likely unaware of them’ (Maiden 1893).

The Bitterbark or Fever-bark tree, Alstonia constricta, yields an intensely bitter bark that was utilised as a febrifuge. However, claims that this bark had antimalarial potential similar to that of Cinchona bark, and the alkaloid quinine, have not been substantiated. (Image courtesy Russell Cumming)

A

B A: Corkwood (Duboisia myoporoides) bark; B: corky bark of Caldcluvia paniculosa; C: Corkwood Laurel (Endiandra sieberi). (Images courtesy Peter Woodard)

C During the 1900s the investigation of alkaloids extracted from the Solanaceae family in Australia proved to be a considerable chemical challenge. Indeed, to this day, new discoveries continue to be made. The fact that the manufacture and supply of hyoscyamine from Australia proved to be a spectacular international success was probably a rather unexpected development for all concerned. At the outbreak of World War II, a number of botanical drug resources were held in high esteem. This included atropine, which was obtained from Belladonna (Atropa belladonna) and Henbane (Hyoscyamus spp.): ‘Hyoscine was reclaimed from the

mother liquors after hyoscyamine had been extracted from the same plants, and before the Second World War was used mainly in association with morphine as an analgesic at childbirth and as an hypnotic agent in certain mental disorders. As the war progressed the demand for hyoscine increased, since it was found of great value in the treatment of bomb shock and also as a preventative of sea- and air-sickness’ (Barnard 1952). Hyoscine was a particularly attractive proposition because it was an extremely potent drug that required only a minuscule dose to be effective. Economically speaking, it was a perfect drug enterprise when resources were becoming progressively more scarce. The indispensable value of these drugs to medical services throughout the war is something few of us would appreciate today. The observations of Professor HJG Hines (1947) highlight the vital role of the Australian supplies: ‘Hyoscine is the most efficacious prophylactic known agent against sea- and air-sickness; and the safe landing in fit condition of thousands of troops in sea- and airborne invasions has been made possible through the extensive use of this drug, which has been practically all supplied from the eastern coastal districts of Australia’. Thirty years later Professor Geoffrey Blainey (1977) was even more eloquent: parcels of the drug were being flown – some of the most precious air cargoes ever to leave Australia – to the United

PITURI: A MYSTERIOUS NARCOTIC States and Britain. When in 1944 D Day approached and the Allied invasion of France was about to begin, tens of thousands of troops, before they sailed from England in the invading armada, were dosed with this traditional aboriginal drug. For Australia was now the world’s main source of hyoscine and the pre-operative medication atropine, both of which were extracted by chemists from species of the Duboisia tree. Here, in 1944, was the greatest armada in the history of man, setting out towards a turning point in history; and much of the success of that armada depended on a drug which had been discovered by forgotten men and women in Ancient Australia.

The Puzzle of Chemical Variation

A comprehensive technical account of hyoscine in the 1949 British Pharmaceutical Codex makes interesting reading, and explains the many uses of this drug: Hyoscine hydrobromide [= scopolamine hydrobromide] produces mydriasis and accommodation for distance more quickly, but for a shorter time, than atropine … A dose of 0.6 milligram (1/100 grain) is useful for the prevention of seasickness. Hyoscine hydrobromide has been recommended in the treatment of morphine and alcohol addicts … Pre-medication with hyoscine hydrobromide … and morphine … allays the fears of the patient, reduces the amount of anaesthetic required, and diminishes pain on recovery of consciousness. Hyoscine in doses of 0.3–0.6 milligram (1/200–1/100 grain) thrice daily by mouth reduces the tremors and movements in paralysis agitans and chorea, and relieves the muscular rigidity and salivation of post-encephalitic parkinsonism.11 Hyoscine has been used to produce amnesia and partial analgesia in labour; the method, which is known as ‘twilight sleep’, depends upon the administration of hyoscine with morphine and the exclusion of all external disturbing factors.

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v. Muell. is said to be still richer in alkaloid, which is chiefly amorphous scopolamine; while the leaves of Datura arborea L. (Brugmansia arborea Steud.) and of D. cornigera Hooker (Brugmansia Knightii Hort.), natives of South America, acclimatized in Queensland, contain a mixture of hyoscyamine and atropine’ (Remington 1918). Mention of the alkaloidal components of species introduced to Australia more than a century ago is worthy of note. Generally known as ‘Angel’s Trumpets’, these plants, while beautiful, are now considered to be weeds in many tropical countries. Brugmansia suaveolens and Brugmansia x candida are the species naturalised in New South Wales and Queensland, respectively. The task of unravelling the chemical puzzle of the Duboisia genus was not to be fully resolved until the 1950s. The Corkwood Duboisia (Duboisia myoporoides) was discovered to have a different alkaloid composition to the other species. It contained the tropane alkaloids hyoscine and hyoscyamine. This was quite different from Pituri, which was originally suggested to contain nicotine as the primary compound. The active principle was eventually identified as d-nornicotine, a chemical four times more potent than nicotine. Even after these discoveries, unravelling the pharmacology of these

A comparison of the alkaloid content of Duboisia appeared in 1918: ‘According to the researches of Jos. Lauterer (L. L., 1896), the old leaves and twigs of Duboisia myoporoides, contain hyoscyamine, the fresh young leaves scopolamine, the dried leaves being stronger than are belladonna leaves, and yielding 0.97 per cent. of alkaloid. Duboisia Leichhardtii F. 11 Between 1916 and 1930 there was an outbreak of an epidemic known as ‘encephalitis lethargica’, which primarily affected young people. Those who did not die were often seriously incapacitated. The development of parkinsonian tremors was not uncommon, which responded to the use of scopolamine (Foley 2006). More recently, investigations of similar cases have found a clear link with this disease – which was due to a rare form of Streptococcus bacteria and an abnormal immune response that results in serious brain tissue damage (Anderson 2009; Dale 2004).

Ornamental Angel’s Trumpet, northern Queensland.

Atherton Tablelands,

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plants continued to present an intricate and complex problem. Subsequently, it was found that the chemical composition could vary with the season of collection and stage of maturity – as well as their site of origin. For example, nornicotine was predominant in Northern Territory samples of Pituri, while nicotine levels were higher in Western Australian samples. These discoveries substantiated the profound empirical knowledge of Aboriginal people with regard to these resources. The type of Pituri that was desirable for chewing tobacco purposes was high in nicotine but low in nornicotine. In addition, traces of an aromatic compound, metanicotine, could be present. The chemical variety used for poisoning purposes was completely different – it was high in nornicotine, which was around three times more toxic than nicotine to animals (Watson 1983). The chemical idiosyncrasies of Corkwood Duboisia were found to be similar to those of Pituri. However, seasonal variations in its chemical composition had been appreciated from the early days of the herb’s collection. In 1900 Joseph Maiden recorded: ‘Dr. Finselbach makes the statement that the leaves of D. myoporoides contain rather less alkaloid during the flowering period than later, and recommends them to be collected in Nov. or Dec.’ (Maiden 1900). Later studies clarified the situation with some rather interesting results. Trees grown in the warmer areas of southern Queensland and northern New South Wales contained hyoscine as the dominant alkaloid. Plants grown in the cooler regions of southern New South Wales were characterised by larger amounts of hyoscyamine. Near Killarney in Queensland, yet another chemical type of Corkwood Duboisia was found with low levels of tropane alkaloids, notably nicotine and anabasine. However, the presence of the other components – hyoscyamine, norhyoscyamine, tigloidine, apoatropine and aposcopolamine – could vary greatly (Griffin 1985).

Tigloidine Tigloidine was another alkaloid of pharmaceutical interest that was isolated from Duboisia – although it was present only in small amounts, comprising around 0.15–0.5 per cent

of the total alkaloid content. Tigloidine acts on the nervous system, primarily having a CNS depressive effect with associated antimuscarinic (affecting acetylcholine neurotransmitters), anti-spasmodic, sedative and muscular relaxant actions. Clinically, it was found useful for the control of various neurological disorders including Huntington’s disease, spastic paraplegia and parkinsonian tremors. The drug specifically affected involuntary motor activity, not voluntary movement. Although its properties resembled those of atropine, tigloidine lacked some of the typical side-effects, albeit incidents of euphoria were recorded. However, the exorbitant cost of production in the early 1950s saw investigations into this drug discontinued until its later synthesis (Cribb & Cribb 1981; Foley 2006). The Martindale Extra Pharmacopoeia (26th edition) of 1972 listed the following: ‘Tigloidine hydrobromide is chemically similar to atropine and it has actions similar to some of the actions of atropine. It is, however, almost devoid of anticholinergic effects. It is used in the treatment of muscular rigidity and spasticity, particularly when due to lesions of the upper motor neurone, but its value in these and similar conditions has not been fully established. It should be given with caution to patients with glaucoma.’ A later entry, in the 29th edition (1989), was very similar, noting its use was equivalent to that of atropine sulphate and adding a recommendation for the treatment of parkinsonism. By this time the drug was synthesised. Ultimately, the chemical intricacies of these plants were to prove even more complex than initially anticipated. Professor Len Webb mentioned the distinctive nature of some of the alkaloid variations: ‘one of the most remarkable local examples of this influence was recorded in the leaves of Duboisia myoporoides, which contained about 3% of almost pure hyoscyamine in October, and about the same amount of pure hyoscine in April’ (Webb 1952). Significant alteration in alkaloid accumulation strategies were shown to depend on the life cycle of the leaf. Levels of tropane alkaloids were related to the stage of growth –


a cycle that followed an established pattern. Chemical accumulation was highest during periods of rapid leaf growth, and virtually ceased when full leaf expansion was reached. After this, the alkaloid level remained unchanged until senescence, when the alkaloid losses became quite rapid (Mishra 1998). Seasonal influences were equally important. A more pure, crystalline product was procured during autumn and winter – while the yield during spring and summer contained a syrupy base. The leaf was harvested by cutting back the trees (rather than cropping them) when they were 7–10 months old. They were then trimmed every 7–8 months. This resulted in a shrubby habit that facilitated leaf harvest. However, the trees had only a short life span of around five years. Julia Morton (1977) provided the following harvesting information: The lopped branches from each tree are tied in a bundle and hung on the tree until the end of the working day, when all bundles are gathered and taken to an opensided shed and stocked for further drying, which takes two weeks to a month in warm weather. Removal of the leaves cannot be done by manual threshing, as this releases alkaloid-laden dust injurious to the laborers. It is customary to crush the bundles by running a light tractor over them, then the dry material is sieved through rectangular screens to separate the branches and twigs from the leaves and the leaves are baled or, less often, bagged for transport … Plantings of 300–400 trees per acre (740–980 per hectare) yield about 400 lbs dried leaves per acre (498 kg per hectare). Annual yields of 1 ton of dry leaves per acre have been reported.

The chemical constituents of the Leichhardt Corkwood (Duboisia leichhardtii) were comparable to those of the Corkwood Duboisia. However, Duboisia leichhardtii had one great advantage – its alkaloid content was less variable than that of D. myoporoides. Unfortunately, during the war, harvesting had been done from wild plants – a practice that resulted in the wholesale clearing of scrublands. The devastation of native floral stocks was considerable. In some places only an occasional tree could be sighted in a neglected paddock or struggling by the roadside. To ensure a reliable source of hyoscyamine, the establishment of plantation crops was essential. Sadly, the cultivation of Duboisia leichhardtii was to become an enterprise fraught with difficulty, for much of the harvested seed was infertile. This appeared to be an almost insurmountable obstacle until the discovery

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Duboisia leichhardtii. (Courtesy Keith AW Williams, Native Plants of Queensland, Vol. 3)

of a process that used gibberellic acid to significantly enhance the germination rate. Eventually, the Corkwood Duboisia and Leichhardt Corkwood were used to develop a hybrid that yielded hyoscine in quantities up to 3 per cent. After this, high-yielding cultivars were developed with an alkaloid yield of around 5 per cent – a discovery that allowed the enterprise to become a commercial reality (Griffin 1985).

Farmed Duboisia fields, Australia. For over half a century a high-yielding hybrid that was developed from Duboisia myoporoides and D. leichhardtii in the early 1950s has been managed as a crop resource. Around 1200 tonnes continue to be exported yearly, mainly to West Germany, Switzerland and Japan, for processing. Overseas plantations were established in Ecuador, South America (Evans 2002). (Image courtesy Dorothy & Gary Hurdle)

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Table 9.1 Duboisia: Main Chemical Constituents of Pharmacological Interest Sources: Pearn 1981, Lassak & McCarthy 1990, Foley 2006. Species Duboisia myoporoides Corkwood Duboisia

Location/Range East Coast: Cape York, Queensland – to southern New South Wales coast.

Constituents Different chemical races vary according to location. Around 20 tropane alkaloids, and six non-tropane alkaloids, have been identified. Tropane alkaloids: hyoscine (scopolamine), hyoscyamine, tigloidine, isopelletierine etc. Other alkaloids: nicotine, nornicotine, anabasine, hygrine, myrtine, pelletierine, tetramethylputrescine. Triterpene: ursolic acid.* Note: Nicotine-containing specimens have been discovered that are native to New Caledonia. They lack hyoscine. Duboisia leichhardtii Inland Queensland – South Tropane alkaloids (5%): hyoscine (scopolamine) 6–46%, Leichhardt Duboisia Burnett region hyoscyamine 10–80%, norhyoscyamine 3–42%. Lesser amounts: tigloidine, apoatropine etc. Variation of hyoscine and hyoscyamine is not as great as in Corkwood Duboisia, but either alkaloid may be dominant in different stands of the trees. Duboisia hopwoodii Central Australia (inland NT, WA Nicotine and nornicotine (up to 25% dry leaf material). Pituri & SA); Western Australia South Small amounts of hyoscine (scopolamine) and hyoscyamine. Australia; NSW & Queensland (a Note: Hyoscine may be absent. few sites) Duboisia myoporoides–leich- Farmed commercially in southHyoscine and hyoscyamine (high alkaloid-yielding varieties): hardtii hybrids east Queensland (Kingaroy 5–7% total alkaloids of which around 50% is scopolamine. area, around 40% owned by Boehringer Ingelheim Plantations) Note: Also farmed by Boehringer Ingelheim in Brazil (Arapongas, Parana) Duboisia arenitensis Northern Territory – limited to Low alkaloid content and not currently of commercial interest. Arnhem Land * A study showing that ursolic acid had effective insect antifeedant activity sourced the raw material from the stems and leaves of Duboisia myoporoides (Shukla 1996).

Table 9.2 Australian Solanaceae and their Alkaloidal Constituents Based on Griffin & Lin (2000). Genus

Species

Alkaloids (and other constituents)

Anthocercis

Anthocercis viscosa Anthocercis fasciculata

Hyoscyamine. Tropane alkaloids based on teloidine were also isolated.

Anthocercis littorea Anthocercis ilicifolia

Tropane alkaloids differed: mainly littorine and meteloidine.

Anthocercis genistoides

Meteloidine as the major alkaloid.

Cyphanthera

Cyphanthera anthocercidea (formerly frondosa) Cyphanthera odgersii Cyphanthera tasmanica

Anthotroche

Anthotroche myoporoides Anthotroche pannosa Anthotroche walcottii

Hyoscyamine, apoatropine.

Grammosolen

Grammosolen dixonii

Alkaloid spectrum Cyphanthera.

Crenidium

Crenidium spinescens

Eight tropane alkaloids. Hyoscyamine predominated. Also contains anabasine (and ursolic acid).

Symonanthus

Symonanthus aromaticus)

aromaticus

(formerly

Anthocercis Scopolamine and hyoscyamine.

scopolamine,

similar

norhyoscyamine

to

Anthocercis Scopolamine and aposcopolamine.

that

of

and

nicotine-free


Intriguing Australian Relatives Duboisia belongs to the tribe Anthocercideae, which contains six other genera, two of which have been of limited chemical interest – Anthocercis and Cyphanthera contain diverse tropane alkaloids, although scopolamine or hyoscyamine tend to predominate:

Anthocercis viscosa. (Courtesy Melburnian)

Cyphanthera tasmanica. (Courtesy David Morrison)

Anthotroche walcottii. (Courtesy Paul Campbell)

• The oldest classification is Anthocercis, a genus limited to West Australia and South Australia that contains around 12–13 species. • Cyphanthera, which contains 12 species (including a number of species formerly classified as Anthocercis), is the most widespread, extending across the southern part of the continent (New South Wales, Victoria, Tasmania, South Australia, Western Australia). • Three other genera are endemic to Western Australia: Anthotroche (3 species), Crenidium (1 species) and Symonanthus (3 species). • The genus Grammosolen (3 species) extends from Western Australia to South Australia.

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A Toxic Harvest

Field being prepared for Duboisia crop production. (Courtesy Dorothy & Gary Hurdle)

Despite the apparent success of Duboisia cultivation, a practical and rather serious obstacle was to become manifest. Leaf collection relied on hand-harvesting and the alkaloids were easily absorbed through skin contact. Exposure could quickly result in poisoning. The symptoms mainly affected vision, something that Joseph Bancroft had noted in his early appraisals of the drug: ‘I have given Duboisia in asthma and photophobia. It causes much dilatation of the pupil, and indistinct vision, also confusion of intellect, particularly at night, a thirsty dryness of the throat, and loss of taste. At present no valuable results, except the mydriatic, are apparent.’ These classic sideeffects are associated with the use of certain tropane alkaloids. Headache, giddiness and delirium were also mentioned – problems that could be encountered even with the use of eye drops. Occupational exposure was generally characterised by eye reactions (acute mydriasis, conjunctivitis, and cycloplegia12 or ‘cork-eye’). Higher doses resulted in facial flushing and dryness of the mouth. Delirium or depression were only seen with a significant level of exposure. While protective clothing was worn during harvesting and processing, accidental exposure could still occur. In addition, chronic exposure could have serious consequences: neurological problems, lethargy, euphoria and retrograde amnesia. Incidents of poisoning not associated with cultivation were sometimes associated with eating the leaves, albeit a relatively uncommon occurrence: 12 Hyoscine is a powerful cycloplegic drug – it induces paralysis of the ciliary muscle of the eye.

‘The leaves are poisonous (though not violently so) but accidents from them are very rare. Some years ago, two children in the Richmond River district chewed them, and suffered from general nervous and muscular derangement, accompanied by delirium. They recovered’ (Pearn 1981). Another interesting incident involved a few adventurous, somewhat misguided, teenagers who experimented with a brew of the leaves and coffee. They suffered a hallucinogenic intoxication that subsequently landed them in hospital (Pearn 1981).

Success and Failure: the Australian Experience

The period from 1941 to the early 1950s saw impressive advances in Australian hyoscine production on a commercial basis. The Sydneybased pharmaceutical firm Felton, Grimwade & Duerdins (FG & D) undertook the daunting task of ensuring drug supplies. (This company was later to become Drug Houses of Australia; DHA.) Early in World War II company chairman Russell Grimwade was approached by Sir Alan Newton, Chairman of the Australian Defence Forces Medical Equipment Control Committee, with a view to finding locallysourced drugs for an emergency pharmacopoeia. It was Grimwade’s recollections of Dr Bancroft’s work that were to inspire the development of the Australian-based hyoscine and hyoscyamine industry. RJ Smith (1989) reviewed these events: [Grimwade] set about growing drug plants on his property at Westerfield. From all reports, the work that went into the project at F. G. & D. was indeed superb. In an account by the then Chief Chemist, E. I. (Eddie) Rosenblum, the task of producing eight ounces of pure hyoscine hydrobromide was accomplished in only four weeks. The company then expanded its capacity to not only make Australia self-sufficient in wartime but also to supply the Allied Forces with product. It was with justified pride that F. G. & D. were able to supply the whole of the motion sickness drug hyoscine hydrobromide used by the D-Day troops crossing the Channel in June 1944 (Smith 1989).

The Australian suppliers met their goals extraordinarily well and became the sole source of scopolamine to the Allied Forces throughout the entire war effort. The figures were impressive. In 12 years of operation


almost 6,000 kg of alkaloid salts were produced (Smith 1989). Unfortunately, this commercial success was not to last. After the war, government support was withdrawn and subsidies were reduced – a situation that was to take away all incentive for the enterprise. Inevitably, after 1945 research into Duboisia was scaled down. A mere nine years later most development efforts had been abandoned, although a couple of plantation trials persevered. Russell Grimwade summed up his great disappointment in a letter to the Minister for External Affairs, Richard Casey: The bulk of the world’s atropine is being manufactured abroad from Australian leaves by pharmaceutical manufacturers who enjoy much cheaper labour conditions than those prevailing in Australia. A modern and efficient extracting and refining plant which, during the war and the period of the embargo, was working around the clock, to-day stands idle … not less than 12 alkaloids and their salts are now manufactured in Australia. This technical success has now become an economic impossibility owing to lack of governmental support. Australia has few, if any, articles of commerce that have originated from its natural resources and it is unfortunate that lack of official recognition of the circumstances is causing her to lose world dominance in the supply of irreplaceable pharmaceuticals that would have been easily within her grasp (Grimwade 1954).

A Matter of Overseas Development

Overseas interest in the chemistry and potential economic value of the genus continued, mainly by Japanese and German investigators. India, a major importer of Australian Duboisia leaf, undertook substantial research with a view to establishing a local industry. India and Pakistan began to farm Duboisia myoporoides – although crops of commercial worth were not forthcoming (Foley 2006). In 1951 the German pharmaceutical company Boehringer Ingelheim developed a Duboisia-based antispasmodic (spasmolytic) and analgesic drug named Buscopan. A reliable supply of Australiangrown plants was essential for its production. To overcome the problems associated with variable drug yields and to ensure a good supply of raw materials, in the mid-1960s investigations were successfully undertaken with regard to establishing plantationbased crops. The drug was particularly valuable because

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Buscopan. (Courtesy Boehringer Ingelheim Pty Limited)

it lacked the psychotropic effects of scopolamine and was extremely effective in the treatment of gastrointestinal spasm (abdominal pain and cramping, irritable bowel syndrome) and menstrual pain. A breeding program was subsequently instituted that focused on the identification and selection of alkaloidrich genotypes – as well as improved seed germination and pest control. It was an extremely complex undertaking to address the problem of unexpected changes in the alkaloid content of the plant, which continued to be a significant obstacle. Not only did variations occur between different genotypes, clones or hybrid plants – alkaloid levels were also influenced by the age of the tree, environmental conditions (season and location), and even local growing factors (fertilisers, soil type, water supply). Eventually, clones were discovered that were suitable for cultivation and plantations were established in Australia and Brazil. Crop reliability was enhanced by the propagation of selected trees with improved pest resistance and growth characteristics. Strategies were employed to ensure that alkaloid levels were consistent, which allowed maximisation at levels around twice that of the former wartime production. The enduring market for Buscopan has ensured that it has remained an extremely profitable commercial venture (Ohlendorf 1996). Annual production is around 21 tonnes of the active ingredient (scopolamine butylbromide), with the ex-factory price estimated to be in the region of US$250 million (Grynkiewicz & Gadzikowska 2008). The fact that Boehringer was an established drug supplier, with a much better hold on the international market and access to extraordinary research facilities, gave them significant advantages over Australian concerns with regard to drug development. Despite the lack of Australian governmental support, and working against the odds, a few individual growers undertook further crop research.

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Their ability to retain a share of the marketplace, however, was to involve a fairly rocky road and remarkable determination – as chemist Reg Smith explained: A new phase in the duboisia industry commenced in the 1980s with the direct entry of German alkaloid producers into the plantation production of leaf for export to Europe unprocessed. Swiss/Italian interests recently have followed suit. As a consequence … the independent Australian, drug-plant producer (who vigorously defended his right to sell overseas) will [probably] die out and this natural resource will be almost completely overseas controlled. Annual exports of dried Duboisia leaves for 1988–89 amounted to approximately 500 tonnes, 97 per cent of it going to European producers. Conservatively this would give rise to revenue in excess of $A10m when processed into the pure alkaloid salts and derivatives. Further add-on value is gained on processing into finished pharmaceutical products (Smith 1989).

In 1991–92 the gross value of the Duboisia crop to pharmaceutical companies was estimated to be around US$2 million, although the value of the extracted alkaloids was much higher (US$5–15 million). The final product value was thought to be around US$100–150 million. Two Australian companies remained involved in alkaloid extraction on a relatively small scale – Alkaloids of Australia

Corkwood under cultivation for commercial production. (Courtesy Dorothy & Gary Hurdle)

(Kingaroy) and Phytex Australia – and both continue to be involved in drug specialities. In 2002 almost 100,000 kg of leaf was exported with a value of $6,604,439 (Foley 2006). The following comment by Paul Foley is telling: ‘The reasons for the failure of Australian interest to control the industry are many, but foremost were certainly the lack of cooperation between producers regarding research, development and marketing, and Commonwealth Government indifference to the industry after the Second World War’. In 2008, Queensland plantations produced 10–15 tonnes of fresh leaves per hectare: a harvest that can be undertaken three times a year, giving a yield of 2–4 per cent total alkaloids with around 60 per cent hyoscine. In comparison, European resources from Atropa and Datura species have a fairly low yield: 0.2–0.8 per cent total alkaloids, with a low hyoscine content. The Australian crop now supplies the majority of the international pharmaceutical industry with hyoscine (Grynkiewicz & Gadzikowska 2008).

 The use of native narcotic plant material was not restricted to Pituri – although this was preferred. There were also various Native Tobaccos in use across the continent. The story of the discovery, evaluation and chemical character of these plants is equally interesting. While they do not appear to have had the same impact as Duboisia hopwoodii for trading purposes on a continental scale, tobacco was a very familiar commodity, particularly in Central Australia. Surprisingly, Australia has numerous native Nicotiana species, albeit only a few were suitable for use as a form of chewing tobacco. Smoking pipes were later introduced by the Macassan pearl and trepang traders who undertook a yearly pilgrimage to the northern coastline from Sarawak, Indonesia.

Chapter 10

TOBACCO TALES The discovery of Pituri’s narcotic properties and its subsequent pharmacological development was a milestone for Australia’s drug-plant industry. However, Wild or Native Tobacco, another interesting local narcotic from the genus Nicotiana, which was also highly prized by Aboriginal people, was equally intriguing to chemists. A review by J Burton Cleland (1950) mentioned the similarities of their use: The discovery of the narcotic effects of pituri by the natives of south-west Queensland doubtless arose through trial of every possible plant as a source of nourishment during drought. Its sustaining effects during fatigue must have been noted. It was traded in exchange for red ochre from the Mulligan in south-west Queensland as far as Quorn in South Australia. In central Australia it was used as a poison for stupefying emus, its place for chewing by man being taken by several species of true Nicotiana, especially the tall handsome Nicotiana excelsior. Quids of the chewed material, mixed with the alkaline ashes of species of Acacia, are parked behind the ear until again required by the owner or a friend.

If the leaves were in short supply, Wild Tobacco stalks could be chewed or ground to a powder for later use. Nicotiana excelsior is an evening/ night-flowering species with a wonderful jasmine-like perfume. (Courtesy Steve Pedro, flickr)

Aboriginal campsite, Yirrkala, Northern Territory, 30 August 1948. Image by Robert Miller, American-Australian Scientific Expedition to Arnhem Land, Northern Territory. (nla.pic-vn4495123-v)

Wild Tobacco

Early references to the sources of ‘Native Tobacco’ were plagued by confusion with regard to the identification of many Nicotiana species. Various authors noted the use of some species as chewing tobacco, while others disagreed – or the species identification was questionable (Peterson 1979). Some of these herbs were suspected stock poisons, not least because of the known toxicity of nicotine. For a long time Australian scientists found it difficult to determine the true extent of Nicotiana poisoning in animals. In 1887, Thomas Bancroft made the first report on the poisonous qualities of Nicotiana suaveolens: the native tobacco of Australia, an herbaceous plant seldom attaining a height of over two feet, is distributed all over Queensland, and is popularly believed neither to be poisonous nor to possess the action so much admired by the smokers of tobacco. The poisonous nature of this plant was discovered in May, 1886. An extract of the dried plant is very poisonous, in every respect resembling the physiological action of tobacco (Nicotiana Tabacum, Linn.) and of pituri (Duboisia Hopwoodii, F.v.M.). It is 403

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interesting to note that the Australian blacks, to whom tobacco and pituri are such a boon, never discovered that this plant possessed some narcotic action. I came across large quantities of it growing on the Gregory River; the blacks there, although it grew around their camp knew nothing of its action, nor had they even a name for it.

Yet a report by the botanist Richard Helms in 1891 certainly mentioned the use of this species in inland Australia: to find that the natives … use tobacco was a surprise to me. It struck me as peculiar when I noticed their lips and the corner of their mouth being colored with a yellowish-green rim, and attributed it at once to some peculiar food they might have been eating, but later on I discovered that it’s true cause was the sucking of a roll of native tobacco … Whilst these tribes have discovered the stimulating properties of Nicotiana suaveolens, they do not seem to know the more powerful narcotic of ‘pituri’ Duboisia Hopwoodii, which also occurs in many places throughout the same regions (Helms 1896).

The difficulty was not only associated with chemical variations in Duboisia hopwoodii and the ‘Native Tobacco’ plants – but lay also in the botanical classification of the Australian Nicotiana genus which, at the time, was quite rudimentary. ‘New-Holland Tobacco Plant’, Nicotiana suaveolens, by Sydenham Edwards, from Curtis’s Botanical Magazine, Vol. 18, Plate 673, 1803.

Botanical Conundrums

Nicotiana suaveolens. Chapman, flickr)

(Courtesy

Arthur

D.

Nicotiana suaveolens (formerly N. exigua) favours eastern Australia (Victoria and New South Wales), although the herb is also present in Queensland, South Australia and south Western Australia. This species, which is now known as the Austral or Australian Tobacco, has been associated with incidents of stock poisoning even though it can contain very low levels of nicotine – as does Nicotiana velutina. The latter shares the same habitat as Nicotiana suaveolens in southern Queensland and has likewise been associated with incidents of poisoning (Everist 1981). Early toxicology reports are difficult to attribute to Nicotiana suaveolens because of the

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problems with botanical identification. Indeed, for a long time many species were thought to be varieties of this plant: • Nicotiana benthamiana (N. suaveolens var. cordifolia), N. rosulata (N. suaveolens var. rosulata), N. rotundifolia (N. suaveolens var. rotundifolia), N. velutina (N. suaveolens var. debneyi), N. excelsior (N. suaveolens var. excelsior) and N. megalosiphon (N. suaveolens var. longiflora). • Nicotiana goodspeedii, N. debneyi and N. velutina were formerly classified as N. suaveolens var. parviflora.

Nicotiana velutina. (Courtesy Keith AW Williams, Native Plants of Queensland, Vol. 2)

Nicotiana benthamiana, seedling and leaf. (Images from Wikipedia.org, Public Domain)

The question of toxicology was complicated by the fact that the chemical variability of the active components in these plants was something of a mystery. Selwyn Everist explained: ‘because of confusion in classification and the fact that many

Nicotiana benthamiana flower. (Courtesy Charles Andrès CC-by-SA 3.0, Wikimedia Commons)

reports of poisoning have not been supported by botanical specimens it is not possible to identify with certainty the species involved in most cases of native tobacco poisoning recorded in literature. There is a possibility that some species may be virtually nontoxic and there seems some evidence that alkaloid content may vary rapidly from place to place, season to season, even hour to hour, as well as from one species to another’ (Everist 1981). Overall, the genus Nicotiana favours the interior of the Australian continent. There are around 24 native species (a number of which have been newly identified) – as well as a few naturalised species: the Tobacco plant (Nicotiana tabacum), which is primarily found in Queensland, and the South American Tree Tobacco (N. glauca), which is widely naturalised (although it does not favour the northern tropics). Native species considered suitable for narcotic use appear to be limited. Aboriginal people were well aware of the chemical variability of these plants. They knew that only certain areas were suitable for the harvest of reliable quality raw materials. It seems that their experience with local plant resources was, indeed, a very good basis for harvesting operations. The best quality product involved collection of the older leaves only, often from very specific populations – which were known to have more potent effects. In Central Australia five species provided acceptable ‘Wild Tobacco’ resources (Latz 1996; Everist 1981): • Rock Pituri (Nicotiana gossei) and N. excelsior: These species, which have been the two most favoured native tobacco resources, have a fairly similar distribution in Central Australia.

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• Nicotiana benthamiana: is more widespread, ranging from Western Australia to central Australia and western Queensland. • Nicotiana cavicola is restricted to central Western Australia. • The Sandhill Pituri, Nicotiana rosulata subsp. ingulba (syn. N. ingulba) is distributed from Western Australia to Central Australia and South Australia. This species, although frequently used as a source of ‘pituri’, was not regarded as being among the most prized species. Its potency could vary substantially.

Nicotiana rosulata subsp. ingulba (syn. N. ingulba). The Sandhill Pituri is a species that has been utilised as a fish and game poison. It also had a minor medicinal reputation. The juice of the leaves has been applied locally to relieve the itchy rash that can be caused by contact with processionary caterpillar hairs (Latz 1996) – which suggest good antihistamine and anti-inflammatory effects. (Image courtesy Craig Nieminski, flickr)

Nicotiana megalosiphon subsp. megalosiphon. (Courtesy Keith AW Williams, Native Plants of Queensland, Vol. 4)

The use of these plants, however, could differ greatly between the Aboriginal tribes. Perhaps this was linked to the availability of alternative traditional narcotics such as the Duboisia-based pituri, or whether the Nicotiana species found in the local area was considered to have toxic attributes. Those few species that rated little interest as narcotics include: Nicotiana occidentalis, N. simulans, N. megalosiphon and N. velutina. The nicotine content of the latter was low and the plant was highly toxic to stock. Some samples of Nicotiana megalosiphon have even been recorded as containing no nicotine. Nicotine, nornicotine, and/or anabasine are the primary constituents isolated from the native ‘Wild Tobacco’ species. With a total alkaloid content of around 2 per cent, the primary alkaloids were present in varying amounts in the different species (averaging around 0.5 per cent) – although, even today, not all species have been fully analysed. The alkaloid level in normal leaf tobacco (Nicotiana tabacum) can vary between 0.5–9.0 per cent – and the leaf material selected for commercial production purposes has much higher levels than the native Australian species. Even higher amounts can be present in some other American species such as Nicotiana rustica, which can have overall alkaloid levels as high as 18 per cent. This species has substantial insecticidal properties.

Nicotiana tabacum, which has a lower nicotine content than N. rustica, is the main species cultivated for commercial purposes.

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Table 10.1 Australian Nicotiana: Distribution, Use and Chemistry (if known) Species

Distribution and uses (if known) (Peterson 1979; Latz 1996)

Component alkaloids (Everist 1981; Latz 1996; McKenzie 2012) Note: TA = total alkaloids μg/g dm (dry matter)

Nicotiana amplexicaulis

Queensland

TA: leaf 4959; root 7648

Nicotiana benthamiana

WA, NT, Qld Nornicotine: 0.31% Widely used chewing tobacco in Central Australia, but nicotine: 0.48% (plus anabasine). considered inferior if stronger species are available. TA: leaf 3602; root 3826

Nicotiana burbidgeae

SA

Nicotiana cavicola

WA Chewing tobacco mixed with ash from White River Gum bark on Fortescue River.


Nicotiana debneyi

Qld, NSW, Lord Howe Island (naturalised)

Anabasine: up to 1.3% alkaloids 0.46%). TA: leaf 2457; root 3038

Nicotiana excelsior

WA, NT, SA TA: leaf 18902; root 4772 Rare plant or arid inland Australia; used as chewing tobacco – flowers, stalks and leaves chewed and mixed with ash of Acacia aneura and Red Gum: • Plants dried (in sun or over fire) broken up and made into quid, mixed with ash for use as a stimulant. • Also used as a ringworm cure.

Nicotiana glauca Tree Tobacco

Introduced South American species that has become naturalised: Anabasine: 0.62%. WA, NT, SA. Qld, NSW, SA. Growing wild in parts of Western Anabasine: 1–1.3% dry weight of Australia where it has been used as chewing tobacco. the roots, and low concentrations of nicotine (Schep 2009). TA: leaf 15009000 (85% anabasine)

Nicotiana goodspeedii

WA, SA, NSW, Vic

Nicotiana gossei Rock Pituri

NT, SA Nicotine: 0.96–1.1%. Highly preferred species for use as chewing tobacco, mixed with TA: leaf 12169; root 7222 alkaline ash. Extremely important plant in central Australia; highly prized in trade. Chewing plant is said to reduce pangs of thirst and hunger; induces general feeling of well-being.

Nicotiana heterantha

WA

(total


Nicotiana maritima

SA, Vic


Nicotiana megalosiphon

NT, Qld, NSW Widespread in Central Australia; rarely (if ever) used Two subspecies: • subsp. megalosiphon (Qld, NSW). • subsp. sessilifolia (NT, Qld).

Nornicotine: 0.22%. Nicotine: very low or none. TA: leaf 319; root 5566

Nicotiana monoschizocarpa

NT

Nicotiana occidentalis

WA, NT, SA, Qld, NSW Three subspecies: • subsp. hesperis (WA) • subsp. obliqua (WA, NT, SA, Qld, NSW) • subsp. occidentalis (WA)


WA, NT, SA Two subspecies: • subsp. rosulata (WA, NT, SA). • subsp. ingulba (syn. N. ingulba, WA and NT): widespread availability, spinifex areas of Central Australia; commonly used as chewing tobacco, although potency can vary. Sometimes used to poison waterholes to catch game.

Wide variation in potency. Nicotine: 0.33% (‘low potency’ samples). TA: leaf 992; root 3376 subsp. ingulba: TA: leaf 669; root 4804

Nicotiana rosulata Sandhill Pituri

subsp. hesperis: TA: leaf 4108; root 1930

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Nicotiana rotundifolia

WA No uses noted


Nicotiana simulans

WA, NT, SA, Qld, NSW Western Australia: widespread in arid regions. Rarely used as chewing tobacco.


Nicotiana suaveolens

Qld, Vic, NSW

Syn. N. exigua – nicotine (0.008%). TA: leaf 4954–7692; root 6658– 12040

Nicotiana truncata

SA

Nicotiana umbratica

WA


Nicotiana velutina

WA, NT, SA, Qld, NSW, Vic. Common in central Australia; conflicting reports on use – said to be valued in some places, but certainly not in others.

Nicotine (low levels): 0.03–0.12%. TA: leaf 5276; root 24817

Nicotiana wuttkei

Qld (Atherton Tablelands, northern Qld)

Weedy Imports

A couple of American species have become naturalised in Australia and are listed as weeds – the Woodland or South American Tobacco (Nicotiana sylvestris) and the Tree Tobacco (N. glauca). Where the cultivated tobacco (Nicotiana tabacum) has escaped its confines, it is regarded as a particularly noxious pest. The native Velvet Tobacco (Nic-otiana velutina) is another listed weed. The Tree Tobacco (Nicotiana glauca), from Argentina, is an acclimatised species that has been implicated in cases of animal poisoning. This shrub was introduced as an antiscorbutic agent for sheep and just happened to ‘run wild’ in the southern Australian states. Although it is primarily found in South Australia and New South Wales, the plant ranges to southern Western Australia, and extends along the east coast from Victoria into northern Queensland. It has been utilised as a chewing tobacco in Central Australia (Lazarides 1997; Lamp & Collett 1986). American Indian medicine recommended an infusion of Tree Tobacco leaves as a steam bath for rheumatism, while the leaf poultice was applied locally for treating scrofula or inflamed glands of the throat (Moerman 1986).

Nicotiana sylvestris

Tree Tobacco, Nicotiana glauca. (Courtesy Carlos Ross, Wikimedia Commons)

Tobacco as Medicine A Historical Drug Plant Nicotiana is a very ancient genus and is thought to have evolved in the Andean region of South

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Nicotiana tabacum

Nicotiana rustica, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1887.

Nicotiana rustica flower.

America. From here it became distributed throughout the Americas and, via Antarctica, reached Australia and the Pacific in the Gondwanan period. A single species ranged into Namibia, Africa. The vast majority of Nicotiana species (56%) are of South American origin, with significantly less representation (12%) in North America. Australia has the second largest diversity (29%) and there are a few species (3%)

found in Africa and the South Pacific Islands (Kunio 1998). There are around 67 species in the genus overall – of which 24 are found in Australia. Smoking is an ancient custom. Tobacco seeds on archaeological sites in the Americas have been dated from around 100 AD, with pipes being found that are older by around 1,000 years. Only two American species have high levels of nicotine: Nicotiana rustica and N. tabacum. While the origin of both is obscured in antiquity, they are thought to have come from the Bolivian Andes. Nicotiana rustica has been found at archaeological sites in Iowa, dating around 550 AD. Two other species were traditionally utilised for ritual and ceremonial purposes in western North America, Nicotiana quadrivalvis and N. multivalvis. The 1918 Dispensatory of the United States of America provides the following details with regard to tobacco resources: Other species also of Nicotiana are said to be cultivated, especially N. rustica L., which yields the Turkish tobacco and is said to have been the first introduced into Europe, and is thought to have been cultivated by the aborigines of this country, as it is naturalized near the borders of some of our small Northern lakes. The N. quadrivalvis of Pursh [botanist] affords tobacco to the Indians of the Missouri and Columbia Rivers; and N. fruticosa, a native of China, was probably cultivated in Asia before the discovery of this continent by Columbus. Besides these there are N. Persica L., cultivated in Persia, and is the source of Persian tobacco; N. repanda Willd., cultivated in Central and Southern North America; N. bigelovii Wats.,

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary of North America. It is very doubtful, however, whether these plants furnish any large part of the commercial tobacco. Latakia tobacco seems to be the product of the N. Tabacum, and Senator Vidal asserts that N. repanda is not found in Cuba, N. Tabacum being the only species there cultivated. Again, the Persian and Turkish tobacco sold under the name of tumbeki, which has been variously attributed to N. Persica and to N. rustica, is in all probability the product of N. Tabacum (Kew Bulletin, April, 1891).

(Right) Nicotiana tomentosa, by M. Smith, from Curtis’s Botanical Magazine, vol. 118, (1892) – a ‘Wild Tobacco’ from South America (Bolivia and Peru).

Illustration of Nicotiana rustica and N. tabacum showing botanical details of plant, flower, fruit and seed, from E Gilg & K Schumann, Das Pflanzenreich. Hausschatz des Wissens, ca. 1900, published by Kurt Stüber, Tübingen, Germany. (Right) Shiraz Tobacco, Nicotiana persica (N. alata var. persica), from Sydenham Teast Edwards & John Lindley, Edwards’s Botanical Register, Vol. 6, 1833. This is the species of tobacco cultivated in Iran, described as ‘a rather handsome annual, exhaling a faint but pleasant odour in the evening. In Persia it grows 3 or 4 feet high’.

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Nicotiana rustica leaves. (Courtesy F a r m e r Dodds, flickr)

In 1830 CS Rafinesque provided a succinct description of the use of Tobacco: ‘Nauseous narcotic, poisonous weeds, disgusting taste and smell; first used by priests of Indian nations to intoxicate and appear inspired, adopted by the idle savages and the vicious civilized men as a stimulant narcotic to tickle the throat and nose … unless we use the mild kinds or mix it with sweet herbs as the Asiatics and Indians do’ (quoted in Erichsen-Brown 1979). Despite this rather unflattering appraisal and its toxic reputation, Tobacco (Nicotiana tabacum) was once a valued Leaf Tobacco, from British Pharmacopoeia, 1867. medicinal plant of the American Indian away by two or three times using’. He also mentioned people. Much of the herb’s therapeutic reputation has its use for respiratory and gastrointestinal problems: been attributed to its nicotine content – although the ‘It is found by good experience to be available to plant’s chemistry is much more complex. It contains expectorate tough phlegm from the stomach, chest diverse active constituents including pyridine alkaloids and lungs. The juice thereof made into a syrup, or (anabasine, nornicotine), harmala alkaloids (harman, the distilled water of the herb drunk with some sugar, norharman), glucosides (tabacinine, tabacine) and or the smoke taken by a pipe as is usual, but fasting, polyphenolics. helpeth to expel worms, and to ease the pains in the Aside from its great ritual and ceremonial importance, the Tobacco plant was widely used in tribal remedies for its diuretic, anthelmintic, analgesic, cathartic, antispasmodic and sudorific effects – being employed to treat conditions as diverse as colic, cramps, dropsy (oedema), dizziness and fainting. It also had a reputation for being a useful analgesic for toothache and earache. A number of other species were employed similarly – notably Nicotiana rustica, N. bigelovii and N. attenuata, with the latter also being smoked as a treatment for asthma and tuberculosis (Moerman 1986). Even in the mid-1600s Tobacco had gained substantial medical repute in Europe – as Nicholas Culpeper noted: ‘The distilled water is given with some A range of Tobacco products on display at Herberton sugar before the fit of an ague, to lessen it and take it Historical Village, north Queensland.

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head, or megrim [migraine], and the griping pains in the bowels.’ Tobacco leaf had a substantial reputation as a counter-poison against the bites of venomous creatures – and as an antibacterial and healing agent. Certainly, the leaves or roots had useful styptic properties that could stop bleeding from wounds. Applied locally, Tobacco herb was considered effective for insect bites and snakebite – as well as providing a remedy for cuts, sores, boils, herpes1, scrofulous swellings etc. Indeed, Culpeper elaborates that: ‘distilled liquor is good to use in cramps, aches, gout and sciatica, and to heal itches, scabs, and running ulcers, cancers, and all foul sores. The juice is also good for all the said griefs, and to kill lice in children’s heads. The green herb bruised and applied to any green wounds, cureth any fresh wound or cut whatsoever; and the juice put into old sores, both cleanseth and healeth them. There is also made hereof a singular good salve to help imposthumes [abscess], hard tumours2, and other swellings by blows and falls.’ Indeed, the herb’s reputation as an anticancer agent was quite substantial, with the leaf being incorporated into oils and ointments, cooked with animal fats, or mashed with vinegar or brandy for use on all forms of growths (tumours), warts and ulcers (Hartwell 1971).

Australian Paralysis Tick (Ixodes holocyclus); specimens from the Koala Hospital at Port Macquarie, New South Wales. The small tick had not yet started feeding, while the other (which contains around 5 ml blood) had probably been feeding for a couple of days. (Image courtesy Bjørn Christian Tørrissen, Wikimedia Commons, CC-by-SA 3.0 Unported)

Tobacco smoke enema device, showing insertion tube and bellows for blowing smoke up the rectum. From Lehrbuchzeichnung eines Tabakrauchklistiers – a medical textbook published in Berne, Switzerland, 1776.

To b a c c o smoke enema m e d i c a l kit (origin unknown).

1 It was noted to be utilised as a general antiherpetic agent that was effective against herpes virus infections such as ‘cold sores’ of the lips, or even the neurological pain associated with shingles. 2 Scirrhus or scirrus (may be incorrectly spelt schirrus) is a type of hard tumour that usually arises from an induration (hardening) of a gland. This condition frequently develops into cancer.

Tobacco enema preparation, from British Pharmacopoeia, 1867.

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Drawing of tobacco plant and description of the medicinal use of Tobacco from Good’s Family Flora, 1845.

Tobacco stems, leaves and snuff were reputed to destroy all kinds of insects, moths, caterpillars. An old Australian remedy for treating tick paralysis in dogs involved administering a quid of tobacco leaf, with plenty of water, to wash the poison out of its system. Apparently, it was known to be an effective cure for this highly distressing disorder, which often resulted in fatalities (Joan O’Grady, 2011, pers. comm.). Doubtless there are many other old remedies using Tobacco leaves that are no longer used or even remembered. In the mid-1700s, the use of a tobacco smoke enema was considered to have a warming and stimulating effect in conditions characterised by collapse. This included its use (rectally) as a form

of anal ‘artificial respiration’ in cases of drowning. The treatment was also utilised in a variety of rectal and intestinal problems, including obstruction (e.g. hernia, constipation). Although its efficacy was hotly debated for many decades, the practice was deployed for at least a century before it fell out of favour. This may seem a somewhat unorthodox practice – although it cannot be considered any stranger than the idea of coffee enemas, which were initiated in 1917 and continue to be proposed as a cleansing intestinal stimulant to this day. Coffee enemas were even listed in the Merck Manual until 1971 – although there are plenty of risks associated with their use, both physical (e.g. perforation or infection of the bowel) and metabolic (due to induced electrolyte imbalances).

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Risky Business Nicotine Toxicity

doses, or in persons unaccustomed to it, tobacco produces severe nausea, sometimes vomiting, accompanied with profuse perspiration, and great muscular weakness.

Nicotine’s physiological effects were directly influenced by dosage: The alkaloid nicotine is a virulent poison. It primarily excites, and secondarily paralyzes, the ganglia [nerve ends] upon the sympathetic nerves, stimulates the intestinal muscles, and, in sufficient quantities, has a paralytic action upon the motor nerves. As a result of its action upon the sympathetic ganglia, it causes contraction of the blood-vessels with marked increase in the blood pressure, followed, after large doses, with vascular dilatation and fall, of pressure. The pulse rate is at first decreased, later becomes rapid. There is primary increase in the secretion of the salivary and probably of the other glands, followed, after large doses, by paralysis of secretions (Remington 1918).

Tobacco leaves drying. Nicotine can be absorbed through the skin during hand-harvesting of the crop, resulting in ‘green tobacco sickness’. Nicotine is soluble in water, and thus handling wet tobacco leaves can result in substantial absorption, generally resulting in nausea, vomiting, headache, dizziness and weakness – although the symptoms can increase in severity (see Table 10.2) (Schep 2009; Gehlbach 1975). (Image by Jack Delano, 1942)

An official overview of tobacco and nicotine, published in the 1918 Dispensatory of the United States of America, outlines the toxicological considerations associated with these products: Medicinal Properties and Uses.—Tobacco is locally irritant. Snuffed up the nostrils, it excites violent sneezing, and a copious secretion of mucus; chewed, it irritates the mucous membrane of the mouth and increases the flow of saliva; when injected into the rectum, it sometimes operates as a cathartic; and the alkaloid nicotine injected into the cellular tissue of animals evidently produces much pain. In large

The Martindale Extra Pharmacopoeia of 1952 elaborated on the potential toxicity of the drug: ‘Nicotine is one of the most toxic of all drugs and in acute poisoning death may occur within a few minutes due to respiratory failure arising from paralysis of the muscles of respiration. The fatal dose of nicotine for a man is from 40 to 60 mg. Less severe poisoning causes nausea and salivation, headache, dizziness, mental confusion, disturbed hearing and vision, faintness and prostration.’ Incidents of poisoning, which could quickly become life-threatening, are well recorded in the literature. Symptoms involved circulatory collapse, shallow and rapid pulse, ‘cold sweats’, convulsions, loss of consciousness and cardiac arrest (Martindale 1952; Frohne & Pfander 1984). It is an interesting fact that sheep and cattle can tolerate fifty times more nicotine than humans without showing any signs of poisoning. However, in toxic doses, its effect in animals are equally debilitating – depression, muscle tremors, staggering gait, and an inability to rise from the ground. Fatalities can be rapid, occurring within 1–2 hours (Lamp & Collett 1996).

TOBACCO TALES

Nicotine was formerly widely used as an insecticide – albeit an extremely hazardous substance to handle. The drug is rapidly absorbed through the skin and cases of poisoning frequently occurred from its careless use. Torald Sollmann (1949) provided details of some early cases of toxicity: ‘Fatal nicotine poisoning occurs from accidental ingestion of nicotine in insecticides: 288 cases were reported in the registration area of the United States in the five years of 1930 to 1934 … Serious poisoning occurs industrially from inhaled tobacco dust (Burstein, 1927) in nicotine extraction (Genkin et al., 1935) and sometimes through the medicinal use of tobacco, especially by the laity.’ The use of Tobacco leaves on wounds and bruises, or as an enema for worms (especially pinworms), were practices that held considerable risk. Overdoses had serious consequences. The 1918 Dispensatory of the United States of America mentioned: ‘A case of death is on record, occurring in a child eight years old, in consequence of the application of the expressed juice of the leaves to the head, for the cure of tinea capitis [ringworm of the scalp]. Death has also been produced by the inhalation of the smoke’ (Remington 1918). Fatalities could occur within a few minutes – or take hours. The fatal dose of tobacco

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is around 2 grams. Indeed, a single cigar contains enough nicotine to prepare a fatal injection. Chemically, tobacco alkaloids are primarily pyridine-based. These components are classified in two categories according to their chemistry: piperidine (lysine-derived, e.g. anabasine) or pyrrolidine (ornithine-derived, e.g. nicotine). This is of interest because there are other natural compounds in plants that are fairly closely allied in a chemical sense, and it explains why a number of alkaloids possess toxic effects resembling those of nicotine. They include nornicotine and anabasine from the Duboisia genus, as well as anagyrine, which is present in some North American legumes – Lupins (Lupinus spp.) and Wild White Indigo (Baptisia alba). High doses of anagyrine and anabasine3 have shown teratogenic properties (induction of birth defects) in animal studies. Nornicotine is also suspected of inducing developmental abnormalities – but while nicotine is a liver toxin, nornicotine is not. 3 Nicotinic acid is the precursor for nicotinamide and anabasine – as well as arecoline from the Betel Nut (Areca catechu) and ricinine from Castor oil seeds (Ricinus communis). These related pyridine-derived alkaloids have toxic properties, as does coniine from Poison Hemlock (Conium maculatum) (Aniszewski 2007).

Table 10.2 Summary of the Symptoms of Nicotinic Acid Poisoning

(based on Schep 2009) The initial onset of the symptoms of nicotine poisoning (as well as similar alkaloids such as anabasine, coniine and cytisine) is very quick, within 30–90 minutes, because the alkaloid is well absorbed from the gastrointestinal tract. Its distribution throughout the body is equally rapid – and it can cross the blood–brain barrier, the placenta, and is readily absorbed into breast milk. Nicotine is metabolised in the liver and forms numerous metabolites, mainly cotinine (70–80%), which are primarily excreted in the urine. The majority is excreted within 1–4 hours, although anabasine takes longer (around 16 hours) – and the level of excretion is increased with acid urine and by a high urine output (Schep 2009). Body system affected Gastrointestinal Respiratory

Early exposure symptoms (initial stimulation effect) Nausea, vomiting, abdominal pain, excessive salivation Bronchorrhoea (profuse sputum production), tachypnoea (rapid breathing).

Cardiovascular

Hypertension, tachycardia (fast heart beat), pallor

Neurological

Pupillary constriction (miosis), dizziness, headache, ataxia (uncoordinated movement), confusion, tremors, involuntary muscle twitching, seizures (uncommon, can occur with high doses).

Delayed symptoms (depressive effects*) Diarrhoea Respiratory depression: dyspnoea (difficulty breathing), apnoea (periods of stopping breathing). Death: due to severe respiratory depression due to muscular paralysis or cardiovascular collapse. Serious effects on heart rhythm: bradycardia (slowing of the heartbeat), irregular heart beat (dysrhythmia) hypotension and shock. Central nervous system depression: reduced muscle tone and strength, general weakness, lethargy muscle paralysis, coma dilation of the pupil (mydriasis).

*Treatment relies on supportive care measures – with atropine being used to control symptoms of parasympathetic nervous system stimulation: excessive salivation, bronchorrhoea, wheezing, as well as gastrointestinal hyperactivity and bradycardia (see Schep 2009 for full details).

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It is important to note that while anabasine and nornicotine are found in Tobacco in lesser amounts than nicotine, both are more toxic than nicotine. Anabasine has insecticidal attributes and has been investigated for use as a ‘truth drug’ by military forces. Nornicotine, which is naturally present in numerous Nicotiana species (including Tobacco), is a metabolite of nicotine and forms around 10 per cent of its breakdown products in the body. It is therefore not only ingested from the process of smoking tobacco, but is also formed from chewing tobacco or using nicotine patches. In addition, nornicotine is a precursor for the formation of a suspected carcinogenic nitrosamine, N’-nitrosonornicotine. Research has also suggested that nornicotine (which persists in the body longer than nicotine) may be a potent component of tobacco that contributes to the development of diabetes, cancer, ageing and Alzheimer’s disease. Even so, low doses of nornicotine and cytisine have potential for treating nicotine addiction (nicotism; nicotinism). Indeed, the latter has been utilised clinically in Europe for the last four decades.

Alkaloid Relationships

Laburnum seed pods.

Cytisine is a toxic alkaloid with a similar chemical structure and properties to nicotine. Cytisine is found in some common ornamental plants of the Faboideae family, including Laburnum and some Lupins (Lupinus spp.). It is present

in the Common Broom (Cytisus scoparius), the Hawaiian shrub Mamane (Sophora chrysophylla), and the Texan Mescal Bean (Sophora secundiflora4). However, the amount present can vary considerably. Laburnum leaves contain the lowest levels of cytisine (0.3–0.4%), while the level in the flower is higher (0.9%). Quite high doses can be present in seeds (1–2%) (Schep 2009) – while the level in the Mescal Bean is much lower (0.23%) (Barceloux 2008). The British Herbal Pharmacopoeia (1983) lists Broom Tops (from Cytisus scoparius) as possessing cardioactive, peripheral vasoconstrictive and diuretic properties. The herb has been utilised for the treatment of cardiac disorders (oedema of cardiac origin, myocardial weakness, tachycardia), including palpitations with lowered blood pressure (hypotension) – although its cardiotonic properties should be avoided in individuals suffering hypertension. The remedy also has an antihaemorrhagic effect that made it useful for excessive menstrual bleeding. The side-effects of toxic doses of cytisine are similar (but not necessarily identical) to nicotine toxicity: nausea, vomiting, heart pain, headache, convulsions, delirium, paralysis and

The leaves of the Laburnum or Golden Chain Tree (Laburnum anagyroides) provided a Tobacco substitute during World War II in Europe. The seeds, which are toxic, were utilised as a purgative and emetic in American Indian ceremonies. The tincture was formerly recommended in Europe for respiratory disorders (cough, breathing problems including asthma), nerve pain (neuralgia), headaches, insomnia and constipation (Barceloux 2008). (Image courtesy CC-by-SA Jean-François Gaffard) 4 This plant should not to be confused with the Mescal Button Cactus or Peyote (Lophophora williamsii).

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respiratory distress – with fatalities resulting from respiratory failure. Despite this, some of these plants have been used as recreational drugs because cytisine and other component alkaloids (sparteine, N,N-dimethyltryptamine) have neurological effects with hallucinogenic potential similar to mescaline (Barceloux 2008). However, given the toxicology of these plants, experimentation would be equally likely to have unpleasant consequences. Chemically, the fact that cytisine is a lysinederived alkaloid shows some interesting links with other plant alkaloids (Aniszewski 2007): • Q uinolizidine compounds: including lupinine and lupanine from Lupins, and sparteine from the Common Broom. • Lysine-derived piperidine alkaloids: piperine from Black Pepper (Piper nigrum) and other Piper species; and pelletierine which is found in the Corkwood Duboisia.

Common Broom (Cytisus scoparius) from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1887.

Anagyrine, cytisine and pelletierine from the Merck Index, 5th edition, 1940.

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• L obeline and lobelanine from Lobelia inflata have a similar toxic reputation to cytisine. • Pomegranate (Punica granatum; stem and root bark) also contains pelletierine and pseudopelletierine. L-lysine is also an important alkaloid • precursor with interesting toxicological associations for some Australian plants: swainsonine from the Darling or Poison Peas (Swainsona spp.); castanospermine from Blackbean (Castanospermum australe5). These indolizidine alkaloids (a pyrrolizidine and quinolizidine combination) have been of interest for the development of anti-AIDS drugs (Aniszewski 2007).

regarding the reliance that native Australians had on the Tobacco trade:

With regard to Tobacco and Pituri, humanity at large has endorsed the conclusions arrived at by the uncivilised man. The first thing now offered by the European traveller to a newly-discovered savage race is tobacco. I was much struck with this Tobacco-want when passing through Torres Straits lately. Steaming slowly among the islands of that calm sea the vessel encountered a native and his wife in a bark canoe. The only word they used was ‘Tabac, tabac!’ A loaf of bread was thrown to them, but this did not satisfy; and in the wake of the steamer there could still be heard the cry, ‘Tabac, tabac!’ (Bancroft 1885).

Ingenious Tobacco Pipes

5 Additional details are available in Volume 3.

A Local Tobacco Trade

Bulk packaging for tobacco and cigarettes, once commonly sold in local grocery stores. (Display from Herberton Historical Village, north Queensland)

Tobacco has been a familiar commodity in the Australian tropics over the centuries. Long ago, Asian traders and fishermen had introduced the habit of pipe-smoking to the region. It seems that the addictive potential of Tobacco quickly become familiar wherever the drug was traded. In 1879 Joseph Bancroft made the following sad observation

Aboriginal with an11010951-16)

smoking

pipe.

(nla.pic-

Tobacco was a highly valued by Aboriginals and Islanders as a trade commodity. The habit of smoking pipes was probably introduced by Macassan traders from Asia, and reinforced

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On their expedition to the Cape York Peninsula in 1867 the Jardine brothers recounted similar tales:

Aiau, the garden boy, lighting a bamboo pipe for Asav. Bamboo pipes were utilised in Papua New Guinea and the Torres Strait Islands. (Sarah Chinnery photographic collection of New Guinea 1934–37.) (nla.pic-vn4553907-v)

during subsequent periods of European exploration. Macassan (Indonesian) fisherman traditionally came to Australia’s northern shores for the harvest of trepang (a type of ‘sea cucumber’) and pearls. Around a thousand men made the trip yearly to set up camp at sites ranging from the Kimberley of Western Australia to the Gulf of Carpentaria in Queensland. Tobacco and long-stemmed pipes were among the goods they bartered with the Aboriginal residents. Joseph Bancroft mentioned: ‘In the north it was not unusual to find a description of mild tobacco in the dillybags of the natives along with a pipe or pipes – one kind being not unlike a cigar-tube made by the Toredo navalis [a marine worm] in perforating the roots of the mangroves, destroying the root and leaving a shelly crust behind it; but as this description can only be procured on salt water, natives in the interior make a rude pipe of a soft stone, the tube usually very short, of a pithy wood or a joint of a reed’ (Bancroft 1885). Other inventive forms of smoking apparatus were devised. The bowl of Macassan pipes was sometimes made from the claw of a large mangrove crab. The stems of the Black Orchid (Cymbidium canaliculatum) could be crushed and the fibres then packed as a plug in the bottom of the bowl to prevent the smoke leaking out (Levitt 1981).

All these people are much addicted to smoking. Tobacco is used by them in preference when it can be got. Before its introduction, or when it was not procurable from the Europeans, the leaves of a large spreading tree, a species of Eugenia [Syzygium], was, and is still used. These leaves must possess some strong deleterious or narcotic property. I was for some time puzzled to assign a cause for so many of the natives being scarred by burns. Nearly every one shows some marks of burning, and some of them are crippled and disfigured by fire in a frightful manner. They smoke to such excess as to become quite insensible, and in that state they fall into their campfires, and receive the injuries mentioned. The pipe used is a singular instrument for the purpose. It is a hollow bamboo arbour 2½ feet long, and as thick as a quart bottle; one of the smoking party fills this in turn with smoke from a funnel-shaped bowl, in which the tobacco is placed by blowing it through a hole at one end of the tube. When filled it is handed to some one who inhales and swallows as much of the smoke as he can, passing the pipe on to his neighbour. I have seen a smoker so much affected by one dose as to lie helpless for some minutes afterwards (quoted in Byerley 1994).

Very similar reports were made by Europeans when they first encountered the use of tobacco in the Americas. In 1901 Walter Roth recorded additional details of its use and the inventive use of a bamboo smoking apparatus: With very few exceptions, tobacco is now known to, and indulged in, by most of the blacks throughout North Queensland: among such exceptions are the natives of Bentinck and Mornington Islands. During the present year, when visiting the latter, some four men were presented with pipes and tobacco, but before they could be prevented, two of them swallowed, without even chewing, the half-pieces of plug given them: they apparently thought it an article of food, and accordingly one ran into the forest, when he soon returned with a bark troughful of cooked fish, which, under the special circumstances of a first visit, common courtesy compelled me at least to taste. Where European pipes and tobacco are scarce, segments of bamboo – indigenous, obtained in barter, or washed ashore – are brought into requisition. The one extremity of such a segment is closed, with bee’s wax if necessary, and a small hole drilled at the side in its proximity. Tobacco-smoke from any ordinary pipe is expelled into the open extremity of the bamboo,

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whence it is inhaled through the drilled aperture by the other individuals to whom it may be handed. The process may be reversed, the smoke being expelled into the smaller, and exhaled at the larger, opening. On other occasions the bamboo may be closed at both ends, two holes being drilled laterally, one at either extremity, each answering its purpose as before. No matter these variations, the segment acts as a reservoir, not only in preventing waste, but also in enabling several individuals to enjoy the benefits of the one pipeful of tobacco. In addition to exhaling in the ordinary fashion – through the mouth – smoke is very commonly ejected through the nostrils.

Tobacco Substitutes

Native Ragwort (Pterocaulon (Courtesy Russell Cumming)

sphacelatum).

Throughout Australia various herbal alternatives to Tobacco or Pituri were pressed into service during times of scarcity. Plants that were employed as a form of ‘bush tobacco’ included Native Ragworts (Pterocaulon serrulatum, P. sphacelatum), Sneezeweeds (Centipeda spp.) and a Wild Tomato (Solanum ellipticum). Lillypilly leaves (Syzygium sp.) were smoked at Cape York, Queensland. The Cattle Bush (Trichodesma zeylanicum) was employed in Arnhem Land in the Northern Territory, and Stemodia lythrifolia in Western Australia. The dried leaves of the ‘Bitter Bush’ (Adriana glabrata) provided another tobacco substitute near Gladstone, Queensland (Low 1990). The term ‘Wild Tobacco’ has also been used for Solanum mauritianum – a species in the same family (Solanaceae) as Tobacco, albeit not closely related. This is a naturalised shrub

The sun-dried leaves of Pterocaulon serrulatum were ground until soft and then used as a chewing tobacco, which was said to taste similar to Log Cabin tobacco. The leaves and stem were also decocted for medicinal use. The wash was used as a treatment for itchy skin disorders (Wightman 1994). (Image courtesy Natalie Tapson, flickr)

with a pioneering habit that favours the edge of rainforest clearings, notably in the high rainfall regions of the New South Wales and Queensland coasts – although it does range south to Victoria and South Australia. It is distinguished by dusky-green leaves that have a soft, velvety character, and pretty violet starshaped flowers. The native possums and birds are quite partial to the edible yellow berries. Indeed, Brown Cuckoo-doves even take up residence in fruiting shrubs, defending their crop against other birds (Crome 1990). While the shrub can be browsed by stock, there have been rare reports of poisoning. Wild Tobacco has not been associated with incidents of human poisoning in Australia and the fruits were widely eaten by the early colonists (Everist 1981).

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A Goodenia Narcotic?

Solanum mauritianum: herb, fruit and seeds, flower. (Below) The Granadilla, a Passiflora vine of Central American origins, was used as a tobacco substitute in northern Queensland. This unusual observation was made by Walter Roth (1901): ‘When tobacco is not procurable at Mapoon, the aboriginals will smoke Granadilla (Passiflora quadrangularis) leaves, but I do not know of any indigenous plants utilised elsewhere at such times’. Granadilla must have been an early ornamental import into the Australian tropics.

Goodenia ovata, from Henry Andrews, Botanists Repository comprising Colour’d Engravings of Rare and New Plants ONLY with Botanical Descriptions in Latin and English after the Linnaean System, Henry Andrews (author & publisher), T Bensley (printer), London, 1797.

Goodenia ovata.

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A common yellow-flowered desert herb known as the Hairy Goodenia (Goodenia lunata) was occasionally used as a tobacco alternative in Central Australia – usually as a last resort. The leaves were crushed on a flat stone and mixed with ash for use as a chewing tobacco, although initially its use often resulted in a headache. The herb does not contain nicotine or related compounds, although its use as an animal poison does suggest toxic potential (Low 1990; Latz 1996). A few members of the genus, notably Goodenia glauca and G. ovata, have been suspected stock poisons (Webb 1948). Chemical investigations have isolated very small amounts of alkaloids in four species: Goodenia bellidifolia (0.006%), G. rotundifolia (0.01%), G. stelligera (0.006%) and G. subintegra (0.03%) – although investigations found they were negative for anti-tumour activity (Collins 1990). Even today, little appears to be known regarding the medicinal potential of Goodenia, although a couple of species have been used therapeutically. The roots of a Western Australian species, possibly Goodenia scaevolina, were chewed and the juice swallowed to alleviate cough in Broome (Webb 1969a). Joseph Maiden recorded an interesting anecdotal use of another as a sedative: ‘A species of Goodenia is supposed to be used by the native gins to cause their young children to sleep while on long journeys but it is not clear which is used or how it is administered (Bailey). Many plants of this natural order contain a tonic bitter which does not seem to have been critically examined’ (Maiden 1889). Lobelia quadrangularis. The dried herb has been utilised as a form of ‘bush tobacco’ – and was frequently mixed with commercial chewing tobacco (Nicotiana tabacum) and bark ash of Eucalyptus camaldulensis (Smith 1993). (Image courtesy Craig Nieminski)

The Goodenia genus (Goodeniaceae family) contains around 218 species in Australia, as well as a few overseas representatives. Despite their unique Australian character, these attractive yellow-flowered herbs, which could have great potential in the horticultural trade, are not common in cultivation. The Hop Goodenia (Goodenia ovata), pictured here, is a small, hairless shrub of eastern Australia. This alkaloid-containing species also has ursolic acid in the leaves. In Tasmania, an infusion of the twigs and leaves was taken as an anti-diabetic remedy (Webb 1948, 1969a).

Native Campanulaceae The Genus Lobelia The genus Lobelia has a worldwide distribution, although its primary centre of diversity is on the American continent, with a natural range from California to Brazil. A secondary centre is located in the Hawaiian Islands. Overall there are around 400 species in Lobelia, although this may change with classification alterations. In general, members of the Campanulaceae family contain a milky sap that has acrid and irritant effects. Many of these herbs also possess undesirable emetic properties. There are 36 native Australian Lobelia species, a number of which were formerly classified as Pratia and Rapuntium. Isotoma and Wahlenbergia are the other native genera placed in the Campanulaceae – although there are also a few naturalised species in different genera:

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Numerous Lobelia species have been introduced as ornamentals – among them are the American Torch Lobelia or Mexican Lobelia (Lobelia laxiflora), the South African Edging Lobelia or Blue Lobelia (L. erinus), the Mexican Scarlet Lobelia (L. splendens syn. L. fulgens), and the South American L. tupa. Some of these, such as the Blue Lobelia, have escaped from cultivation to acquire a weedy status.

Lobelia arnhemiaca is a tropical native species from northern Australia. (Courtesy Cuzza fin, Wikimedia Commons, CC-by-SA 3.0 Unported)

Lobelia membranacea is a lovely native species found along the entire Queensland coastline, favouring damp nooks and rocky crannies. (Image on left courtesy David Tng, flickr)

Campanula (C. rapunculoides), Grammatotheca (G. bergiana), Hippobroma (H. longifolia), Monopsis (M. debilis) and Triodanis (T. perfoliata). The Australian species of Lobelia do not appear to be amenable to cultivation due to specific mycorrhizal associations. This means that they need fungal partners to ensure their growth and such an arrangement can be difficult to reproduce under cultivated conditions.

The ornamental Lobelia tupa originates from Chile and is characterised by unusual, yet elegant, brilliant red flowers – their upper lip tipped with white. The leaves were known as ‘Devil’s Tobacco’ and smoked by the Mapuche Indians as a narcotic which was reputed to induce hallucinogenic stupors – although there is some uncertainty regarding the extent of these effects. The juice of the plant was also used as an analgesic for treating toothache (Duke 1985).

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The Australian Campanulaceae genera Isotoma and Lobelia contain a number of species with therapeutic potential that suggest similarities to a few American medicinal plants. Perhaps the best known medicinal relative is the anti-asthmatic herb Lobelia (Lobelia inflata) – a species that was formerly thought to merit its own botanical classification, the Lobeliaceae. The herb achieved a measure of fame in medical circles as an antispasmodic for the treatment of asthma and chronic bronchitis, as well as being useful for relieving gastrointestinal tract spasm.

As early as 1911 the British Pharmaceutical Codex officially recognised the use of the herb, and the 1949 edition noted: ‘The action of lobelia is chiefly due to the presence of lobeline. It has been given as simple tincture and as ethereal tincture [prepared with ether], often with iodides, in the treatment of bronchial asthma and chronic bronchitis’. The 1963 edition made similar recommendations. Although this was perhaps the most valid use of the herb, it also gained something of a reputation, somewhat undeservedly, as a ‘cure-all’. Its use would certainly have been limited by dosage considerations, as large amounts (particularly of the isolated alkaloid lobeline) were toxic, eliciting cathartic and emetic effects – which earned it the unattractive nickname of ‘pukeweed’. In a practice that echoes the use of Lobelia by herbalists, the vapour from an attractive native herb known as Rock Isotome (Isotoma petraea) was used to treat respiratory disorders by Aboriginal people. The leaf was employed as an inhalant to help relieve

Lobelia and Lobeline, from the Merck Index, 5th edition, 1940. Lobelia inflata was not the only species used medicinally. The British Pharmaceutical Codex (BPC) of 1949 listed two other plants as alternative sources of Indian Lobelia – Lobelia excelsa and L. nicotianifolia. The internal use of these herbs was usually as an alcohol-based tincture, which was a more concentrated form of medicine when compared with traditional water-based infusions.

Ethereal tincture of Lobelia, Drug Houses of Australia Pty Ltd. (Herberton Historical Village, north Queensland)

Lobelia (Lobelia inflata) is an effective anti-asthmatic herb with a long history of use for the relief of respiratory spasm. American Indians smoked the leaves for asthma, bronchitis, sore throat and cough. It was even reputed to be effective for alleviating the dreaded whooping cough. The herb was also noted to have sedative and diaphoretic properties. Lobelia was also added to many herbal formulations as it was thought to enhance the actions of the other herbal ingredients.

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425 Lobelia nicotianifolia. (Courtesy Dinesh Valke, flickr)

Isotoma anethifolia is one of the native Isotoma of northern New South Wales that is known to contain alkaloids. (Courtesy MG Jefferies)

dyspnoea (difficult breathing), asthma, or wheezing after strenuous exertion (Barr 1993). Some Australian Isotoma species appear to contain lobeline and related compounds that are characteristic of the Lobelia genus. Certainly, alkaloids are present in Isotoma axillaris, I. anethifolia and I. petraea – with the latter two species containing compounds with ‘lobeline-like activity’ (Collins 1990). The traditional use of Lobelia has been largely supported by studies of the chemical lobeline, which is present in the genus in variable amounts. It is the primary component of Lobelia inflata and L. cardinalis, with smaller amounts in L. siphilitica. Lobeline has respiratory stimulant activities, and is analeptic (central nervous stimulant and restorative). Some effects are similar to nicotine, albeit less potent. This initially led to the use of Lobelia inflata as a major ingredient in anti-smoking mixtures to help with withdrawal symptoms – although later formulations included lobeline in preference to the herb itself. However, recent clinical trials have not supported the anti-smoking effects of a sublingual preparation of lobeline sulphate (Glover 2010). The plant chemistry of the genus is complex and there are some other compounds of interest in Lobelia. Experimentally, isolobinine has demonstrated antiasthmatic, antitussive and hypertensive properties, while lobelidine has analeptic activity (Harborne 1999; Manske 1955).

The leaf infusion of the ‘Wild Tobacco’ of India, Lobelia nicotianifolia, has a medicinal reputation as an antiseptic, despite the leaves and seeds being considered acrid and poisonous. In Kerala, the stem bark has been utilised to relieve toothache (applied locally), while the leaf juice was used for preventing tinea pedis on the feet (Silja 2008). The roots have also been utilised as an antidotal remedy for scorpion sting. However, exposure to the fresh leaf sap runs the risk of developing dermatitis. An analysis of the alkaloid content of this species showed seasonal variation, with the highest levels in October and November – the lobeline content of 1–1.8 per cent was higher than that of Lobelia inflata (0.3–0.4%). While this Wild Tobacco did not show clinical benefits for asthmatic patients, in combination with potassium iodide and tincture of belladonna a synergistic antispasmodic action has been demonstrated (Satyavati 1987).

The Cardinal Flower (Lobelia cardinalis) of the Americas was regarded as having properties similar to L. inflata – and was used as an antispasmodic, anthelmintic, nervine (nerve tonic) and diuretic medicine.

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Great Blue Lobelia

Great Blue Lobelia (Lobelia siphilitica, syn. L. syphilitica in the older literature).

The Great Blue Lobelia of Canada and America has similar properties to Lobelia inflata – although its effect was considered to be weaker. The Cherokee and Iroquois Indians utilised the herb as an analgesic and it was popularly added into many pain-relief remedies. The leaf poultice was applied locally for headache relief, or the plant taken to ease rheumatic pain. The leaf infusion was reputed to act as a febrifuge to ease fever, or to alleviate coughing and croup. The root infusion was regarded as being useful for stomach troubles and worm infestations. Additionally, the root tea was used as a remedy for syphilis, while the leaves or root could be applied to promote the healing of sores. This versatile plant could even be used as a snuff to stop nosebleeds. The Pale-spike Lobelia (Lobelia spicata) also had emetic and healing properties. It was applied to heal sores located on the jaw or neck, and used as a wash to treat ‘bad blood’ – which suggests a ‘cleansing’ antibacterial effect. The root infusion also provided a remedy for ‘shaking and trembling’ of the arms (Moerman 1986), which may have been linked to a sedative effect of the herb.

A Replacement Pituri

Isotoma is a small genus of herbs from the Bluebell family (Campanulaceae) found in Oceania, Australia and the West Indies. There are 14 native species. The Rock Isotome (Isotoma petraea) is a decorative shrub with lovely pale blue flowers that inhabits Australia’s dry interior, favouring rocky habitats. (Image courtesy Russell Cumming)

The Rock Isotome or Wild Tobacco (Isotoma petraea), which belongs to a small genus of outback Australian herbs, was reputed to have narcotic and stimulant properties. Dried and powdered, the plant was combined with equal amounts of Mulga (Acacia aneura) ash to release the alkaloid component – and was used similarly to Pituri. Rock Isotome was also said to reinforce the narcotic effects of various lowpotency forms of ‘wild tobacco’ (Nicotiana spp.) – albeit used with great care as the plant also had a toxic reputation (Latz 1996; Lassak & McCarthy 1992). Medicinally, the herb has been employed as an analgesic with an alkaline Mulga admixture – and in the treatment of colds (Lassak & McCarthy 1992). In the 1960s Professor Len Webb noted its use as a ‘pain deadener’ in Western Australia. At the Mount Margaret Mission, Kalgoorlie: ‘a little of the dust is put on the tongue and swallowed and creates a burning and deadening sensation in the stomach’. At

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the Coamo Newbery Mission, ‘the people here are quite keen on it but only chew the dry sticks’ (Webb 1969a). In Central Australia, the Pitjantjatjara tribe utilised the crushed foliage of Rock Isotome as a poultice for the relief of severe headache (Latz 1996). Fresh, the Rock Isotome herb contains an acrid irritant sap that can cause temporary blindness with eye contact: ‘The sap is stated to be intensely bitter to taste and to be very irritant to the eye’ (Everist 1981). The West Indian species Isotoma longiflora (now Hippobroma longiflora) had a similar irritating effect on the eye – and in the United States was regarded as toxic to stock. It contained an ‘acrid poison’, as well as alkaloidal substances that affected the nervous system and heart. If swallowed, the juice produced a burning sensation in the mouth and throat, although the finely pulped leaves were said to be useful for treating toothache (Burkill 1935). One assumes that the latter recommendation only utilised minute quantities. In Yucatan the herb was used as an anti-asthmatic remedy – as well as for the treatment of bronchitis and syphilis, wound healing, and as a cure for epilepsy. Despite this, it is really too irritant to be recommended for medicinal purposes. It contains the toxic compound lobelanidine, which is also found in Lobelia inflata.

Isotoma longiflora (now Hippobroma longiflora). (Courtesy Tau’olunga, Wikimedia Commons, CCby-SA 3.0 Unported)

Woodbridge Poison (Isotoma hypocrateriformis). This attractive small herb is one of the Western Australian species that has been a suspected stock poison, although little appears to be known about its chemical components. It is found throughout the southwest, ranging from Geraldton to Esperance. (Image courtesy Ian Wallace).

Watercolour by Ellis Rowan of Isotoma hypocrateriformis (between 1870 and 1921). (Wikimedia Commons, Public Domain)

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There has been a resurgence of interest in the possible anti-addictive potential of lobeline for treating stimulant addiction associated with amphetamine and methamphetamine. While lobeline acts on nicotinic receptors in a similar manner to nicotine, it has no structural chemical resemblance to nicotine. Lobeline does, however, alter dopamine levels, inhibiting its uptake and promoting its release – and it is the latter that appears to be linked to a desire for repetition of the drug experience. Recent studies have shown that lobeline has antagonistic effects on opioid receptors, which also give it potential for treating problems associated with other addictive drugs such as heroin (Hart 2010; Dwoskin & Crooks 2002; Miller 2001). Lobeline derivatives (lobelaine, nor-lobelaine) have therefore been investigated for their suitability as antiaddiction treatments (Nickell 2010). In addition, the compound β-amyrin palmitate, which has been isolated from Lobelia inflata, has shown sedative and anti-depressant activities (Subarnas 1993, 1992a, 1992b). Interestingly, recent Chinese studies of lobeline have also suggested that this compound has anticancer potential in human breast cancer cells (Chen 2009; Ma & Wink 2008).

There are diverse other herbal remedies that could also be useful for treating addictive disorders. Hypericum (Hypericum perfoliatum) has excellent mood-stabilising and anti-depressive activity. The mental restorative properties of Gotu Kola (Centella asiatica) and Brahmi (Bacopa monnieri) would likewise be of interest.

The Chinese Lobelia

Ban Bin Lian (Lobelia), a traditional Chinese herb.

The Chinese herb Lobelia chinensis has a widespread distribution from China and Japan to India, Bangladesh, Nepal, Indochina (Cambodia, Laos, Thailand, Vietnam) and Malesia (Indonesia, Malaysia). This species contains similar compounds (lobeline, lobelanine, lobelanidine, isolobelanine etc.) to the American Lobelia – although it is used quite differently. The remedy possesses substantial diuretic properties, useful for treating fluid retention and oedema. It has been employed as an antiinflammatory and detoxicant in gastrointestinal infections (enteritis, dysentery), tonsillitis, and inflamed or infected skin conditions such as eczema, carbuncles and furuncles. It is also applicable for the treatment of schistosomiasis (a parasitic disease), cirrhosis of the liver with fluid retention, and as a local application for wasp stings or snake bite. Experimentally, Chinese Lobelia has demonstrated diuretic and hypotensive properties, as well as a broad range of antifungal activity. However, its use is traditionally contraindicated in patients who are weak and debilitated (Bensky & Gamble 1986; Yeung 1985).

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Recently, investigations have suggested Lobelia chinensis extracts have antiviral (antiHSV 1) potential. Over 46 compounds have been isolated from herbal extracts – including scoparone, which had antioxidant properties, and lobechine, with anti-inflammatory potential (Kuo 2011, 2008). Other components include coumarins (e.g. fraxinol), as well as flavonoids with antioxidant and anti-inflammatory properties – apigenin, quercetin, luteolin and linarin (Chen 2010; Han 2009).

Whiteroot or Purple Pratia (Lobelia purpurascens), Poison Pratia (Lobelia concolor) and Lobelia darlingensis, as well as Poison Lobelia (Lobelia pratioides) have been listed as weeds in Australia. (Image courtesy Russell Cumming)

The American Lobelia laxiflora (Mexican Cardinal Flower) is another species that has shown interesting anti-inflammatory activity (Philipov 1998). It is found around Adelaide in South Australia, one presumes as a garden escapee. (Image courtesy Stan Shebs, Wikimedia Commons, CC-by-SA 3.0 Unported)

Whiteroot: Toxin or Medicine?

Poison Lobelia (Lobelia pratioides) is primarily found in Victoria and Tasmania. (Courtesy Melburnian)

The Whiteroot or Purple Pratia (Lobelia purpurascens, formerly Pratia purpurascens) is another native lobeline-containing herb with some particularly unappealing associations, as exemplified by the titles Pukeweed, Vomit-wort and Gag-root. These fairly odious common names graphically describe its effects. Whiteroot, which exudes a toxic white latex, has long been identified as a stock poison in Australia. Despite this, the herb once gained a reputation as an antidote for snake bite, particularly for animals. In 1889 Mr HJ Lane of Macksville in northern New South Wales sent some samples to Joseph Maiden, who commented: ‘[he] announces that the blacks of the Macleay River District use it as a remedy in snake-bite. He states that the blacks “make a decoction of the herb, and give the animal bitten by the snake about 3 or 4 fluid oz. From all I can learn it is only given once. The quantity of the herb is about a handful gathered green”.’ Maiden mentions isolating lobeline from the herb, about which he commented: ‘Dr. T. L. Bancroft kindly informs me that this species contains the same active properties as L. inflata, and might be used as a substitute for it’. He was certainly aware of the emetic and expectorant effects of this compound – and continued with a story of the use of the herb in Aboriginal legends: ‘A correspondent from the Bellinger writes a blood-curdling yarn about a black snake and an iguana [goanna] having a fight. Black snake bites iguana – iguana feeling unwell scampers off for a mouthful of Lobelia purpurascens, and comes

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back to continue his encounter with the snake. Another informant tells me that the effect of Lobelia on the iguana is to make him vomit up any snake-poison. I have had a number of letters and conversations, from which I understand that this belief in L. inflata as an antidote to snake-poison is very generally held in the northern rivers’ (Maiden 1894). Interestingly, Chinese Lobelia was also utilised as an anti-venom remedy for treating snake bites (Tian 1996).

remainder in the evening. It would appear that the dose used was well below that causing the discomforting reactions for which the plant was famous. The effect of the remedy appears to be linked to the antispasmodic properties of lobeline, which would be efficacious for easing the smooth muscle spasm of the urinary tract. However, the use of this herb in inexperienced hands could well have undesirable side-effects. Therefore, unfortunately, there have been serious reservations regarding its general therapeutic use.

Lobelia pedunculata (formerly Pratia pedunculata). A number of Lobelia ornamentals, which were formerly classified as Pratia, are considered toxic – although it is difficult to determine the true extent of their poisonous qualities. They include the fruits of the Australian the Trailing Pratia (Lobelia pedunculata, formerly Pratia pedunculata) and the New Zealand Blue or White Star Pratia (L. angulata, formerly Pratia angulata, and its cultivar ‘Treadwellii’). Other suspect plants include the New Zealand species known as Chatham Island Pratia (L. arenaria, formerly Pratia arenaria) and the Mountain Pratia (L. macrodon, formerly Pratia macrodon) (Wilson 1997). (Image courtesy Eric Hunt, flickr)

There have been a couple of other medicinal uses associated with this species – albeit the plant is considered a toxic weed that is unsuitable for cultivation. A report in the Australian Wild Herb Bulletin (Letters, September 2000) mentions its deployment for urinary and bladder infections. In a number of cases of kidney inflammation or similar problems, a lack of success with conventional and herbal treatments led to the use of Whiteroot – ‘the relief in all cases has been immediate’. The dose was eight leaves per cup of boiled water, which was left to steep for ten minutes. For two days, half a cup (with added water) was taken in the morning and the

The popular ornamental Lobelia nummularia (formerly Pratia nummularia) has a wide distribution in China and Southeast Asia (Taiwan, Indo-China), ranging to the Indian subcontinent and Malesia (Indonesia, Malaysia, Papua New Guinea, the Philippines). It has been utilised in Taiwan as a remedy for diabetes, irregular menstruation, inflammatory disorders and rheumatism. It was also traditionally recommended as a treatment for malarial fevers and tumours (Ho 1995). (Upper image courtesy Lin, Cheng Tao, flickr; lower image courtesy Thanh Tung, flickr)

TOBACCO TALES

 The evaluation of native Australian stimulants such as Nicotiana and Lobelia is far from over. Indeed, so little is known about the latter that much remains conjecture. Even though lobeline has been subject to investigation, the value and role of associated components in the genus and related species is largely unknown. Certainly, the value of Lobelia inflata as a herbal remedy for asthma deserves better investigation, particularly as many anti-asthmatic drugs have serious side-effects. Such studies may well help to understand the chemistry of our native species. The situation with regard to Whiteroot (Lobelia purpurascens) as an antispasmodic remedy is another interesting avenue worthy of review.

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Equally intriguing is the remarkable medicinal value of steroidal substances from the Solanaceae (Solanum genus) and yams (Dioscorea spp.). These compounds have been the mainstay of an extraordinarily profitable arm of the drug industry since their discovery in the 1940s. They have not only been utilised as anti-inflammatory corticosteroid drugs – their value also lies in contraceptives and anabolic steroids. Yet few who use these products today would appreciate the fact that the package of pills from the pharmacy had its origins in herbal discoveries and chemical innovations over seven decades ago. The influence of these drugs on medical practice ushered in a new era of effective therapies, drug discovery and toxic side-effects – none of which should be taken for granted.

West MacDonnell Ranges, Northern Territory. The vast plains of Central Australia are home to some rather remarkable flora. In addition to the characteristic Australian Eucalypts and Acacias there are Native Tobaccos, the narcotic Pituri and the aromatic Mint Bushes. The diversity of plants that survive the extremely challenging conditions also includes numerous species of Solanum, notably the ‘Bush Tomatoes’ – and a wide range of tuberous root crops, among which the Native Yams are highly valued. (Image courtesy Craig Nieminski, flickr)

Chapter 11

STEROIDS FROM YAMS Dioscorea: Steroidal Substances

Steroids play an indispensable role in conventional medical practice. The commercial production of the steroid-based pharmaceuticals that are so common today originated from a discovery in 1943 by the American chemist Russell Earl Marker which enabled the conversion of steroidal sapogenins to progesterone. This was the breakthrough that allowed plant steroid extraction to become a viable concern. As a result, certain Wild Yams (Dioscorea species) achieved recognition as an extremely valuable natural product resource. Indeed, these drugs were to be responsible for an international social revolution with the widespread availability of hormonal drugs, notably the oral contraceptive pill.

The extraction of steroidal substances from Dioscorea was to become a mainstay in the development of a multi-billion dollar branch of the pharmaceutical industry.1 In 1975, a comprehensive review of steroidal sapogenin resources summarised the value of these natural resources: Steroidal sapogenins are of considerable economic importance as precursors of many pharmacologicallyactive steroids, including corticosteroids, hormones and oral contraceptives. Diosgenin is the most important sapogenin from an economic standpoint and, although it occurs in several plant families, it is extracted almost entirely from Dioscorea species. Other steroidal sapogenins and steroids are also used as starting materials for the synthesis of pharmacologically-active steroids, but diosgenin is of supreme importance. Hardman (1969) estimated that over 1,000 tonnes per annum of diosgenin would be required throughout the world by 1973. This contrasts with Bammi (1972) who estimated that world consumption is somewhere between 250 and 350 tonnes. There was a world shortage of diosgenin in 1974 (Blunden 1975).

Dioscorea macrostachya (syn. D. mexicana). During the search for sapogenin-containing flora, Russell Marker found that the Mexican Yam was a particularly rich diosgenin resource. Prior to this, hormones had been extracted from the gonads and adrenal glands of animals, although the yield was pitifully small. Until 1970 the wild Mexican Yam was the primary source of raw materials for the extraction of diosgenin, which was essential for the manufacture of the contraceptive pill. It took the Mexican government’s nationalisation of the industry, and ridiculous price increases, to provide serious impetus for the search for alternative natural sources of the drug. (Image courtesy Amada44, Wikimedia Commons, CC-by-SA 3.0 Unported) 432

By 1972, Mexican wild yam harvests were massive, around 30 million plants per annum (Oliver-Bever 1972). Not unexpectedly, the dependence of the industry on natural plant stocks quickly resulted in a conservation crisis. The situation required innovative solutions, which were to act as an impetus to the search for alternative raw materials: ‘The steroid industry is dependent upon the collection of wild Dioscorea 1 Initially the monetary rewards were quite astronomical. In 1942 Marker produced 3 kilograms of progesterone from 10 tonnes of Dioscorea tuber – which, at that time, had a value of $80 per gram (US$240,000). This was equivalent to around $3 million in 2009 (ACS 1999). Prior to this, progesterone had been $200 per gram in 1940, although with higher production levels the price fell to 30 cents per gram in 1955 (Senate Hearings 1956, published 1957).

STEROIDS FROM YAMS

Dioscorea elephantipes. The Elephant’s Foot Yam from South Africa is one of the African Dioscorea that was harvested for use as a diosgenin resource. It is an impressive member of the genus that is often found as a cultivated pot plant due to the distinctive decorative knobby appearance of its caudex (top of the tuber). The Mexican Yam (Dioscorea macrostachya), which also yields a massive tuber, is very similar in appearance. (Image courtesy Natalie Tapson)

plants, but as the demand for diosgenin increases, the need to cultivate either diosgenin-containing plants or other suitable sapogenin-containing plants becomes essential’ (Blunden 1975). Reliable farmed supplies became a matter of considerable importance: wild sources of Dioscorea appear to be running out in some areas and it is becoming more difficult and expensive to exploit previously untapped wild sources. At least two governments (India and Mexico) have introduced legislation aimed at preventing the total eradication of wild species by demanding that only part of the tuber be harvested, thus allowing natural regeneration to occur. It is clear that the steroid industry will require an increasing supply of diosgenin or of other suitable compounds in the future and cultivation of the necessary species would seem to be the best way of satisfying this need (Blunden 1975).

The American chemist William Summer Johnson achieved total synthesis of progesterone in 1971 – although, surprisingly enough, this was not to be a major force for change. The most influential factor that directly altered the marketplace and affected world prices was commercial. In the 1980s China began to produce large amounts of high-quality natural

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diosgenin at a reasonable price – a development that made the continued use of plant-based raw materials economically viable. The following comment, from an editorial in the Lancet of June 1994, attests to the remarkable contribution of the genus Dioscorea to drug production: ‘Plants have proved invaluable as inexpensive sources of “feedstock” molecules that can be readily transformed into drugs: thus, development of the steroid-based oral contraceptives would have been virtually impossible without plentiful supplies of compounds from the processing of the steroidal components of plants such as yams (Dioscorea spp) and sisal (Agave spp)’. Synthetic corticosteroids derived from natural products continue to provide a wide range of steroidal substances – primarily anabolic steroids, anti-inflammatory corticosteroids, and contraceptives. Processing, although relatively straightforward, does involve complex chemical conversion of the original steroidal components. The importance of these steroids (mainly diosgenin) as raw materials for commercial drug manufacture is often under-appreciated. Today Mexico, Guatemala, Costa Rica, China and India are the main producers of diosgenin – primarily from Dioscorea floribunda and D. composita, with D. deltoidea and D. prazeri from the Himalayas being important resources in India. In 2007 bulk steroid production levels were estimated at around 550–650 tonnes of diosgenin with a market value of US$500 million (Singh & Kaushal 2007). It is important to note that diosgenin undergoes substantial change during chemical and microbial processing before yielding drug-quality steroids. The natural effects of plant-based diosgenin product differ substantially from the steroidal substances it is ultimately used to produce. Thus a great deal of debate has surrounded the use of natural ‘Wild Yam’ creams, directly prepared from the tuber, as a hormonal treatment. Steroidal precursors in the yam are thought to have similar effects to diosgenin. However, in contrast to hormonal drug supplementation, the body does not recognise these yam components as its own hormones – although it appears to utilise them in a similar manner. Overall, studies have not fully unravelled the complex chemistry involved in the medicinal use of Wild Yams, nor their hormonal potential – although some species have definitely

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shown benefits for cholesterol levels, cardiovascular activity and antioxidant properties (Son 2007; Wu 2005).

A Dietary Hormonal Regulator?

Another investigation into Dioscorea alata (cv. Tainung No. 2), which adds support to this hormonal effect, indicates that tuber extracts activated oestrogen receptors (Cheng 2007). Cooking methods can seriously influence the level of steroidal saponins. A study of the Taiwanese yam cultivar Dioscorea pseudojaponica Yamamoto showed that saponin levels decreased in proportion to the time the vegetable was cooked – except with steaming. Frying gave the greatest loss (93–97%); baking was somewhat less (67–74%). The loss with microwave cooking depended on the time taken – resulting in losses anywhere between 10–84 per cent over 3–10 minutes (depending on time, and type of steroidal glycoside). However, while diosgenin survived most cooking processes, it appeared to be eliminated by steaming (Lin 2006).

A Wild Harvest Dioscorea alata: flowering vine. (Courtesy Kim & Forest Starr, Hawaii)

It is important to appreciate the fact that Wild Yam herbal preparations contain a range of chemicals that influence the activity of the natural product. An interesting clinical study of the dietary incorporation of Wild Yam (390 g daily of Dioscorea alata) confirmed an influence on hormone levels – significant increases in serum concentrations of estrone (26%), sex hormone-binding globulin (SHBG) (9.5%), and increased estradiol (27%). Various other hormonal parameters were not affected (DHEA: dehydroepiandrosterone sulphate; androstenedione, testosterone, follicular stimulating hormone, luteinising hormone). Urinary concentrations of a genotoxic metabolite of oestrogen (16ɑ-hydroxyestrone) were significantly decreased – by 37 per cent (Hsu 2011; Wu 2005). Benefits regarding antioxidant status and lipid functions were also observed.

Triangular winged fruit–seed capsules are characteristic of many species in the Dioscorea genus. Some species also yield a soft berry-like fruit.

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Table 11.1 The Dioscorea Genus as a Source of Diosgenin and Herbal Medicines

The main saponins of interest in yams are dioscin, gracillin, and prosapogenins of dioscin. The levels present can vary substantially: dioscin 2.4% w/w and diosgenin around 0.004% w/w in the cultivated yam, while wild yam levels were 0.12–0.48% (Son 2007). The saponin content of Dioscorea tubers increases with age and are at optimum levels when the plant first sheds its leaves (Satyavati 1976). Commercial steroids are produced by hydrolysis of yam saponins. (Dioscin is closely related in a chemical sense to solamargine, which is found in many Solanum species.) Species utilised (country) Dioscorea collettii, D. pathaica, D. nipponica China

Details of steroid content

Notes on investigations (if any)

Three species are primarily employed in China for steroid manufacture: 1,000 tons of diosgenin produced per annum (Yuan 2007). It takes between 3 to 5 years for the tuber to mature, with sapogenin levels varying from 1–8%; average yield 1–2% diosgenin (Satyavati 1976; Evans 2002).

D. nipponica: Japanese Yam. Used in China for preparation of a commercial drug (containing 35% total steroidal saponins) for the treatment of coronary heart disease (Qin 2009). Starch* is a by-product of the diosgenin industry in China: 16,000 tonnes of Dioscorea starch per annum (Yuan 2007). Tissue cultures derived from D. tokoro seedlings can be used for synthesis of tokorogenin (0·1%), diosgenin, yonogenin, β-sitosterol, stigmasterol, campesterol and cholesterol (Tomita 1969). D. prazeri: tuber has toxic attributes and has been used as an effective insecticide for lice, as well as a fish-poison (Satyavati 1976). Deltonine, isolated from D. deltoidea, has demonstrated post-coital contraceptive properties, anti-ovulatory and oxytocic activities (Boikova 1990). Folk medicine: use of D. mexicana as an antiarthritic remedy; it is also reputed to have abortifacient activity. Studies have shown extracts had an oxytocin-like activity*** (Jayme 1993).

Dioscorea tokoro Japan

Sapogenin level of 1.0% in this species (Martin 1969**).

Dioscorea prazeri (syn. D. clarkei) Dioscorea deltoidea India

Rich diosgenin resources: used as raw material for diosgenin extraction.

Dioscorea mexicana (syn D. macrostachya), Dioscorea composita Mexico, Central America

Dioscin is the main saponin in the tubers of these species; D. mexicana also contains glycosides that are similar to ecdysteroids (insect moulting and sex hormones), which have insecticidal activity (Lang 1991). Diosgenin yield: D. floribunda average yield around 5%; D. composita 3–4% (Dawson 1991).

Dioscorea floribunda Guatemala; cultivated in India Dioscorea sylvatica Africa: Transvaal, Natal

Dioscorea zingiberensis Africa

Diosgenin: 5.9% in rhizome (Satyavati 1976).

Antibacterial activity: extracts of D. sylvatica (tuber bark) have shown antibacterial activity against Escherichia coli. Dioscorea dregeana (tuber bark) extracts were active against Pseudomonas aeruginosa (Kelmanson 2000). China: steroidal saponins sourced from this species and D. nipponica are widely used in China for treating cardiovascular diseases (Qin 2009). Recent innovations in production techniques have lead to the diosgenin yield of the cultured cells reached substantial increases (3-fold increase) in production from D. zingiberensis (yield 5.25 mg/L) (Zhang 2009). In addition, a fungus from this yam yields an antibacterial compound beauvericin (Xu 2010, 2008).

* Until recently the starch was regarded as a waste product and treated as such – being flushed down the river with the sewage. An interest in minimising this type of waste has accompanied new applications for the food industry (bread, cereals, feedstuffs), with a greater interest in recycling product development (Yuan 2007). ** This reference contains a comprehensive list of Dioscorea species containing sapogenin. *** Oxytocin has strong hormonal influences and is important during the birthing process and for breast milk release. Among its many other effects is an influence on brain function and emotional wellbeing.

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Folk-healing Traditions

In Chinese medicine the Dioscorea genus has an extraordinarily long history of medicinal use. The Reverend GA Stuart noted that the yam capsules or ‘berries’ were claimed to have ‘stronger medicinal powers than is possessed by the yam itself. Tonic and restorative virtues are ascribed to them. To the tubers of the several kinds of yam mentioned in the Pen-t’sao are ascribed cooling and tonic properties. They are said to benefit the spirits, promote flesh, and, when

Dioscorea bulbifera vine. (Image courtesy Kim & Forest Starr)

Dioscorea bulbifera vine and bulbils.

taken habitually, brighten the intellect and prolong life. Astringent properties in diarrhoea are also ascribed to them, as well as some virtue in polyuria [excessive urination]. As a poultice they are applied to carbuncles, boils, and incipient abscesses’ (Stuart 1911). The rhizome of the Air-Potato Yam (Dioscorea bulbifera) had diverse interesting applications. In China the tubers and bulbils were reputed to have detoxicant, expectorant, febrifugal, diuretic and alterative attributes. In India Dioscorea bulbifera and D. alata were employed for the treatment of piles, dysentery and syphilis, or applied locally to ulceration (Satyavati 1976). Support for some of these uses comes from investigations showing that Dioscorea bulbifera (root and tuber) had positive antifungal activity against Candida albicans. Other species with antifungal properties include Dioscorea alata (extract of the peel), as well as the compounds deltoside and deltonine from D. deltoidea (Aderiye 1996, Vasiukova 1977). The fungicidal properties of chitinase E, sourced from Dioscorea opposita, even showed potential for use as a biodegradable antifungal agent for fruit crops such as strawberries. This has the potential to provide a less toxic alternative to conventional fungicides (Karasuda 2003). Dioscorea cayenensis also contains a saponin with antifungal activity against Candida – albeit not as active as ketoconazole (Sautour 2004).

Dioscorea opposita granulated herb for medicinal use. The Chinese herb Shan Yao, which has traditionally been utilised as an antidiabetic remedy, is also considered suitable as a tonic for kidney and lung function (urinary disorders, asthma, cough) – as well as other symptoms of ‘weakness’: leucorrhoea, spermatorrhoea, chronic diarrhoea and appetite loss (Yeung 1985). (Image courtesy Cathay Herbal, Sydney)

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Table 11.2 Traditional Medicinal Uses of Dioscorea Yams

The use of numerous Dioscorea species across the world appears to be very similar, with the promotion of wound healing, and antibacterial activity, being among their more desirable attributes. The natural anti-inflammatory and anti-arthritic properties of Dioscorea yams are likely to be due, at least in part, to diosgenin. However, yams contain a number of other components (including phenolics, notably flavonoids) with equally interesting pharmaceutical potential that could contribute to their efficacy (Dykman 1998). Therapeutic use Antibacterial and antifungal

Anti-inflammatory and detoxicant

Details Dioscorea hispida In Indonesia: a concoction incorporating the tuber was applied to whitlows (an infected nail) and for treating leprosy sores (Hirschhorn 1983). Malaysia: tuber was pounded with lime or turmeric and benzoin for application to sore feet. The leaf decoction was used similarly (Burkill 1935) Chinese medicine: good reputation as a healing agent for skin disorders, foot sores, boils, and erysipelas (an acute form of streptococcal skin infection) (Duke & Ayensu 1985). Dioscorea opposita (D. batatas) has a similar reputation (Yeung 1985). Dioscorea bulbifera Traditionally, the dried yam was recommended to ‘dissolve toxins’: used in the treatment of scrofula, boils, carbuncles (Lou 1997; Chang 1992). Used for purulent (infected, pus-forming) problems, gonorrhoea and syphilis (Duke & Ayensu 1985). Congo: the bulbils provided a dressing for parasitic and fungal skin infections (Burkill 1985). Java and Brazil: remedies for syphilis, diarrhoea and dysentery were prepared from the plant. In India the tuber was used to treat diarrhoea, haemorrhoids and sores. It was also said to be a useful diuretic and an excellent boil dressing (Watt & Breyer-Brandwijk 1962). Other species utilised in Chinese traditions: Dioscorea hypoglauca, D. tokoro and D. septemloba Chinese remedies for the treatment of urinary tract infections characterised by chyluria (milky urine) (Yeung 1985). Dioscorea tokoro (Japan, China): Traditional use in the treatment of genitourinary disorders associated with inflammation and infection, e.g. cystitis or leucorrhoea. Often recommended for chronic nephritis; also used for infected sores (boils, carbuncles); antibacterial, antifungal activity (Bensky & Gamble 1986; Yeung 1985). Dioscorea hispida Tuber decoction was said to have alterative and diuretic attributes useful for chronic rheumatism in India. In Borneo a special syrupy (sugar-infused) tuber decoction was taken internally for the same purpose (Burkill 1935). Dioscorea bulbifera Chinese medicine: used as a general remedy for the dispersal of ‘lumps’ that can occur with inflammatory conditions; also for food poisoning and hernia; taken internally and/or applied externally for snake bite, dog bite and sore throat (Duke & Ayensu 1985; Chang 1992); additional uses for treating sprains, injuries and testicular inflammation (Lou 1997; Hsu 1990). Africa and Madagascar: the dried bulbils applied to heal wounds, sores and inflammatory problems. Congo: bulbils incorporated into a palm oil ointment for the relief of rheumatic pain. Gabon: the crushed bulbils were used similarly, as well as for treating breast problems (Burkill 1985). Africa (Cameroon): D. bulbifera var. sativa used for inflammatory conditions and pain relief. Bulbil extracts have shown experimental antinociceptive activities for inflammatory and neuropathic models of pain. Potent anti-inflammatory activity has been linked to alkaloid derivatives and flavonoids (Mbiantcha 2011; Nguelefack 2010). However, D. bulbifera has shown hepatotoxic potential, and care should be taken to ensure compromised liver function does not occur in clinical practice. Diosbulbin B was identified as a hepatotoxic component of the tuber extract (Liu 2010; Wang 2011a, 2010b; Xu 2011). In contrast, a lyophilised yam preparation has shown liver-protective properties against hepatic fibrosis in animal studies (Chan 2010). Dioscorea hypoglauca, D. tokoro and D. septemloba Chinese medicine: useful anti-inflammatory for arthritic pain. Dioscorea tokoro (D. hypoglauca, D. collettii and D. gracillima also utilised): recommended as an anti-arthritic remedy that could invigorate the blood circulation and act as a muscle relaxant; useful for rheumatic pain and numbness of the limbs. External application as an anti-inflammatory for skin lesions, including eczema (Bensky & Gamble 1986; Yeung 1985). China: D. tokoro rhizome decoction used for treating arthritis, dysuria, prostatitis, rheumatism; resolvent for blood clots (Duke & Ayensu 1985). D. nipponica: Japanese Yam has been traditionally employed as an analgesic, particularly for rheumatic pain, as a muscle relaxant, and to invigorate the circulation (Yeung 1985).

438 Respiratory disorders

Eye disorders

Diabetes and digestive problems

MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary Dioscorea bulbifera India (Andhra Pradesh): pieces of the fresh tuber were pounded with black pepper to make a paste that was mixed with curd and taken for coughs and colds (Vijayakumar & Pullaiah 1998). India (Morni Hills): Round Yam tubers (roasted, peeled and dried) powdered and taken with honey for respiratory problems. There were two forms of the tuber: one with bitter bulbils that was employed for treating severe coughing problems, and one with normal edible tubers that was used for asthmatic conditions (Singh 1995). Chinese medicine: utilised as a styptic for epistaxis (nosebleeds) and bleeding from the lungs (Lou 1997; Hsu 1990). Dioscorea tokoro Respiratory remedy (chronic bronchitis, antispasmodic for asthma). Dioscin has antitussive, expectorant, desensitisation properties; used for treatment of bronchitis (Yeung 1985). D. opposita (D. batatas): has been utilised similarly for dry cough, asthma and phlegmatic congestion (Chang 1992; Yeung 1985). Dioscorea bulbifera The herb has had a somewhat unexpected reputation as an ophthalmic remedy. In the Congo the sap from the vine stems provided eye drops for ‘purulent ophthalmia’ (an eye infection), while on the Ivory Coast the leaf sap was instilled into eyes to promote wakefulness (Burkill 1985). In East Africa a potion was made from the steamed leaf and used to treat ‘pink eye’ (a form of conjunctivitis) (Watt & Breyer-Brandwijk 1962). Dioscorea opposita (D. batatas) Has a reputation for being useful in spleen and stomach disorders; appetite loss, fatigue, and has a particularly good reputation for the treatment of diabetes mellitus (Hsu 2007; Yeung 1985; Duke & Ayensu 1985). Its activity would appear (at least partly) linked to the hypoglycaemic principle dioscoretine. This compound (isolated from the African D. dumetorum) has shown effective and potent anti-diabetic properties in animal experiments. Interestingly, the herbal remedy was found to contain compounds with both hypo- and hyperglycaemic attributes (Gao 2007; Iwu 1990a, 1990b, Undie & Akubue 1986; Verdcourt & Trump 1969). D. opposita and a dioscorea polysaccharide have shown the ability to improve insulin sensitivity – which is important, as insulin resistance is a major problem in type-2 diabetes (Kim 2012; Lee 2011; Hashimoto 2009; Hsu 2007; Gao 2007). A number of other species have shown similar antidiabetic properties: D. alata (Maithili 2011); D. opposita (He 2011); D. bulbifera (Ghosh 2012a); diosgenin from the Bitter Yam (D. polygonoides) from the West Indies (Omoruyi 2006, 2008; McAnuff 2005a, 2005b); and dioscorans from D. japonica (Hikino 1986). The Japanese Yam, D. nipponica, has a similar antidiabetic reputation (Duke & Ayensu 1985). Experimentally, diosgenin from this species has been shown to have potential for preventing or ameliorating diabetic neurodegeneration (diabetic neuropathy) (Kang 2012). An extract from a D. nipponica and D. japonica mixture has similar neuroprotective potential (Kim 2011).

Toxicology Cautions

The poisonous potential of many yams has been linked to the toxin dioscorine – a bitter neurotoxic alkaloid that can cause paralysis of the central nervous system, similar to the action of picrotoxin.2 Certainly dioscorine is present in Dioscorea hispida, and smaller amounts have been found in D. bulbifera and D. pentaphylla3 (Burkill 1935). Dioscorine is the toxic component of the tuber of the African Dioscorea dumetorum, a species with a highly poisonous reputation. Detoxification of Dioscorea dumetorum tubers involved washing for a prolonged period (4–5 days), or it was sliced and then boiled. Salt water was said to be particularly useful for removing the toxic component. Unfortunately, this yam also

provides a clear example of the problems that can result from inadequate processing. Its use as a food has been plagued by disaster for those untutored in the preparation processes and it has been responsible for numerous incidents of fatal poisoning (Iwu 1990; Undie & Akubue 1986; Verdcourt & Trump 1969; Burkill 1935). The culinary use of the Round Yam (Dioscorea bulbifera) was only made possible by equally meticulous processing (see Volume 3). 2 Picrotoxin (aka cocculin) has stimulant and convulsant effects via its action on the process of chemical transmission in the nervous system. Although highly toxic, it can be used to counteract barbiturate poisoning, e.g. from anaesthetics or overdose. It is, however, more often used for neurological research purposes rather than clinical practice. 3 Dioscorine was noted to be accompanied by another alkaloid called dioscoricine, which had similar properties – suggesting the presence of other components with toxic potential.

STEROIDS FROM YAMS

Dioscorea villosa. (Courtesy Tim McCormack)

Reservations have been expressed regarding the use of some other species of Dioscorea. Experimentally, Bitter Yam (Dioscorea polygonoides) sapogenin extracts have shown potential adverse effects on the kidney membrane in animal studies, which suggests that it could aggravate diabetic nephropathy. Extracts of Dioscorea cayenensis, as well as Colocasia esculenta (Taro), showed similar potential – albeit the clinical relevance remains unclear (Omoruyi 2008; McAnuff-Harding 2006; Grindley 2001). Clinical reports of kidney toxicology associated with the use of Dioscorea quinqueloba have also been observed. The recommendation that proper preparation methods should be followed suggests that these side-effects can be avoided. This herb has been traditionally utilised as a cardiovascular remedy (Kim 2012). Australian studies of Dioscorea villosa have likewise suggested that extracts have nephrotoxic potential. Individuals with compromised liver or kidney function should probably avoid its use – as should those taking drugs with toxic potential. Indeed, many conventional medicines can seriously impair kidney and liver function and their use needs to be carefully evaluated (Wojcikowski 2009, 2008). Certainly, more research needs to be done to clarify the situation.

The wild African Yam (Dioscorea dumetorum) has been an important famine food that has been detoxified by the use of clay (Abrahams 2005). It also contains the antidiabetic agent dioscoretine. (Image courtesy Paul Latham, flickr)

Yams for Osteoporosis? In traditional Chinese medicine bone strength is linked to the concept of kidney function. There are many herbs that are known to tonify the kidneys and thereby have a strengthening effect on the musculoskeletal system, notably the lower back and knees. This has inspired research reviews of various herbal remedies to prevent osteoporosis – a loss of bone mass that results from an imbalance in bone metabolism whereby the resorption of old bone cells (osteoclast activity) outstrips the formation of new bone by osteoblasts. Recent studies have suggested that a couple of yam species possess anti-osteoporotic properties. This is of particular interest to prevent bone loss in postmenopausal women. Diosgenin (sourced from Dioscorea villosa4) has shown interesting angiogenic (blood vessel 4 Dioscorea villosa rhizomes can contain good levels of diosgenin (169 +/– 41.8 ppm) – although ‘the individual differences in diosgenin content in the rhizome samples … were extreme, reflecting variability within a population … Dioscorea batatas aerial tubers were more consistent in diosgenin content [126.7 +/– 19.0 ppm] because they were from a single monoclonal parent’. Resource variability is often an important consideration in medicinal plant crops aimed at drug production (Edwards 2002).

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Natural Anti-cholesterol Agents?

There is some very interesting research that has shown Yam rhizomes possess anti-atherogenic, antioxidant and hypolipidaemic properties, supporting their dietary use in cardiovascular conditions. In particular, Yam saponins can reduce cholesterol levels (i.e. hypocholesterolaemic activity) by forming an insoluble complex with cholesterol that prevents its absorption from the small intestine. Diosgenin can promote the faecal excretion of bile acids, which is an indirect route of cholesterol elimination – and a reduction in triglycerides has been seen in animal studies (Miyoshi 2011; Son 2007). Various other studies support the use of Dioscorea (and various steroidal saponin components) as an anti-cholesterol and blood sugar regulation dietary aid:

Chinese Dioscorea Yam.

growth) potential in bone cells that suggests a role for promoting bone formation and fracture healing (Alcantara 2011; Yen 2005). Red Yeast Rice (see ‘Yeasty Red Moulds’, page 442) has also shown benefits for bone production that could be beneficial in osteoporosis, particularly a combination of monacolin K and diosgenin (Chiang 2011; Cho 2010; Wong & Rabie 2008). There are a number of diosgenin-containing Dioscorea species that have shown similar potential – including D. alata, D. septemloba and D. spongiosa (Peng 2011; Xing 2008, 2007; Jin 2006). A water extract of Dioscorea spongiosa had a stimulatory effect on osteoblast formation and inhibited bone resorption. The activity of this steroid-rich species would appear to be due to a complex interaction between the active components (glycosides, diarylheptanoids and lignans etc.) – although methyl protodioscin was of particular interest.5 Moreover, studies have indicated that this species has antiatherosclerotic properties (Yin 2010, 2008, 2005, 2004a, 2004b, 2004c). 5 Methyl protodioscin showed similar activity to the herbal extract: inhibitory effect on decreasing bone mineral content and mineral density, and a stimulant effect on osteoblast (bone cell) proliferation in animal studies (Yin 2004b).

• Dioscorea panthaica and D. japonica var. pseudojaponica: demonstrated anti-cholesterol potential (Kwon 2003; Chen 2003; Ma 2002). • Dioscorea nipponica: protodioscin and diosgenin were isolated as active antihyperlipidaemic components (Wang 2010a). • Dioscorea nipponica: trillin has shown significant anti-hyperlipidaemic and antioxidant properties (Wang 2012). • Dioscorea polygonoides6: sapogenin can alter the ability of the digestive tract to absorb glucose, thereby exerting an inhibitory effect on cholesterol absorption (Omoruyi 2008, 2006). • Dioscorea batatas: it has been suggested that a tuber ‘flour’ could improve digestive function (which includes a supportive effect on normal intestinal bacterial levels), reduce cholesterol and regulate blood sugar (Jeon 2006). • Dioscorea nipponica is of particular interest. An evaluation of over 200 medicinal herbs determined that this species also had good lipaseinhibitory properties that were associated with the presence of dioscin and diosgenin. This was of interest because the inhibition of dietary fat absorption has interesting implications for obesity management. Animal studies found that Dioscorea nipponica significantly limited weight gain during a high fat diet7 (Song 2009; Kwon 2003). 6 Also known as Bitter Jessie, Dioscorea polygonoides is a very bitter species that has been sometimes confused with D. dumetorum.

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Natural yeast-based products have long been utilised in Chinese cooking. In particular, a fermented redyeast rice (RYR; also known as red-mould rice) was considered to have substantial health promoting properties. The isolation of the cholesterol-lowering agent lovastatin (monacolin) from this source inspired an entire generation of anticholesterol (statin) drugs. As a result, a flurry of research investigated different forms of fermented products based on the yeast mould, Monascus purpureus. Some have an intriguing range of therapeutic potential (see ‘Yeasty Red Moulds’, page 442). The use of different substrates as ricealternatives examined monacolin-enriched Dioscorea products, notably Red Mold Dioscorea (RMD, prepared from D. batatas root). The use of the dioscorea substrate resulted in a significant increase in monacolin K production (17.5 mg/g) in comparison to that associated with a traditional rice substrate (8.62 mg/g). The product showed better hypolipidemic effects than the red-yeast rice (RYR) or unfermented Dioscorea. In addition, while the antioxidant properties of RMD were comparable to the yeasted rice, the dioscorea -product demonstrated superior experimental antiathersclerotic and antihypertensive potential. This was attributed to a synergistic effect that involved a range of compounds (sterols, diosgenin, fatty acids, isoflavones etc.) present in Dioscorea root. Natural products, however, tend to have a complex chemistry, and Red Mold Dioscorea is no exception. While the enhanced monacolin K levels were thought to be largely responsible for the anticholesterol effects of RMD, yellow pigments (notably monascin and ankaflavin) were also present that had equally an interesting anti-cholesterol, anti-inflammatory and plaquelowering capacity. Other components of interest in RMD included a higher level of y-aminobutyric acid (GABA), which has hypotensive properties - as well as antioxidant components (dimerumic acid, phenol, tannins) (Shi & Pan 2011; Wu 2009; Lee 2010, 2007a, 2007b, 2006). Clinically, Dioscorea saponins (particularly diosgenin) have been used to moderate the cardiovascular damage 7 Recent studies of oestrogen receptors, which are involved in adipogenesis (fat cell production), have supported this effect. Research investigations are following up these leads for anti-obesity drug development (Xiao 2010).

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associated with atherosclerosis (hardening of the arteries) and hypertension. The process of inflammation is an important consideration, with recent research suggesting that it underpins the development of these conditions. Thus the fact that diosgenin has immunomodulatory properties that are associated with anti-inflammatory and anti-allergic activity supports the clinical use of Dioscorea yams (Huang 2010, 2009; Cachofeiro 2009; Jan 2007). Certainly, powdered and liquid yam products from Dioscorea alata have shown excellent potential as dietary anti-hypertensive agents. The active components may also involve a yam tuber protein named dioscorin (present in Dioscorea alata cultivar Tainung No. 18 and D. batatas) which has shown antihypertensive potential (angiotensin-converting enzyme inhibition) – as well as anti-inflammatory, immunomodulatory and antioxidant activity (Lin 2009a, 2009b; Liu 2009a, Liu 2009b, 2007; Chang 2005; Hsu 2002; Hou 2001, 2002; Araghinikam 1996). Dioscorea opposita tuber mucilage9, which contains dioscorin, also has antihypertensive activity, as well as cholesterol-lowering properties (Nishimura 2011; Nagai & Nagashima 2006). Another species with antihypertensive potential is Dioscorea cirrhosa (Xia & Zhong 2010). Other yams with benefits for cardiovascular disorders include Dioscorea zingiberensis – a high potency diosgenin (95%) extract of which has shown antithrombotic properties (Gong 2011; Li 2010) – while D. bulbifera has demonstrated cardioprotective activity (Jayachandran 2010; Vasanthi 2010). Studies have suggested that additional benefits may result from the use of Yams in the diet or as herbal medicines: • A nxiety relief (anxiolytic): Shan Yao, a preparation of Dioscorea alata var. purpurea (Tainung No. 1) has shown an anxiety-reducing effect that suggests post-menopausal benefits (Ho 2007). This species has been utilised as a diosgenin resource in India (Shah & Lele 2012). 8 Dioscorea alata (cv. Tainung No. 2) has shown antioxidative effects in raised homocysteine levels in animal studies that also suggest a protective role against arteriosclerosis (Chang 2004). 9 A comparison of the hypolipidaemic effect of chemically different tuber mucilages from Colocasia esculenta (arabinogalactan), Fenugreek (galactomannan) and Dioscorea esculenta (glucomannan) showed that the mannan-rich mucilages had the greater hypolipidaemic effect, particularly that from the yam D. esculenta (Boban 2006).

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Yeasty Red Moulds

Chinese Yam tuber slices, for medicinal use.

• M emory: extracts of Dioscorea pseudojaponica Yamamoto, as well as Dioscorea opposita yam (fresh rhizome) and herb (aerial parts), have demonstrated potential benefits for memory disorders associated with neurodegenerative diseases – with diosgenin being among the components showing neuroprotective and antioxidant effects (Chiu 2011, 2009; Yang 2009a; Ma 2005). • Skin care: diosgenin has been proposed as having anti-ageing effects on the skin (Tada 2009). • Gout: total Dioscorea saponins acted to lower uric acid levels in animal studies. High levels of these crystals can concentrate in various joints (notably the big toe) causing inflammation and swelling (Chen 2006). • Thyroid: Dioscorea bulbifera may be beneficial for goitre, which supports its traditional recommendation as an infused wine (tuber steeped in white wine for a week) taken daily (Chang 1992; Hsu 1990).

Red Yeast Rice. (Courtesy Kok Robin at Aziatischeingredienten.nl)

Red Yeast Rice (RYR; also known as Red Yeast Koji) is a traditional Chinese colouring agent used for imparting a distinctive red hue to dishes such as Peking Duck. It has also been utilised in making rice wine, as a food preservative (particularly for fish and meat), and as a herbal remedy. Red Yeast Rice is sourced from a vibrantly coloured yeast mould (Monascus purpureus) grown on cooked rice: the rice substrate is prepared with red wine mash, alum water and the juice of Polygonum grass. Traditionally, this yeasted rice (dried and powdered or as granules) was utilised for gastrointestinal problems (indigestion, diarrhoea, dyspepsia, childhood colic), for improving blood circulation, and to treat injuries such as bruised muscles, or wounds and cuts. The Reverend GA Stuart (1911) recorded the following under the name leaven (Ch’u): The peptic and nutritive properties … are well recognised in the Pentsao, as well as an abortifacient power. They are used largely in digestive disturbances … Still another kind is known as Hung-ch’u. This is made of non-glutinous rice,

STEROIDS FROM YAMS which is washed clean, mixed with ‘mother leaven’ and by a complicated, slow process of fermentation, made into a very efficient form of leaven of a red color, which is much used in fermenting grain for distillation. Its medicinal properties are the same as those of the other forms, but it is specially recommended in post-partum difficulties and the dyspeptic conditions of children.

In more recent times, clinical studies of Red Yeast Rice (RYR) demonstrated significant benefits for reducing total cholesterol levels. In addition, the anti-inflammatory, antioxidant, immunomodulatory and antihypertensive attributes of various preparations were significant (Tseng 2012; Lin 2011; McKenna 2002). However, the level of the active component, monacolin K, was found to vary substantially in dietary supplements. Although side-effects are rare, individuals who suffer from sensitivity to the yeast can experience mild heartburn, abdominal flatulence, dizziness, or an exacerbation of gastritis (McKenna 2002). Monacolin K, which is identical to the drug lovastatin, inspired a new generation of anticholesterol agents.10 The fact that the latter is under patent protection in the United States resulted in a conflict of interest with companies marketing Red Yeast Rice as a dietary supplement.11 However, the monacolin content of the naturally fermented rice is low (1200–2400 mg/day = 10 mg monacolins containing around 5 mg monacolin K), in comparison to the recommended drug dose (20– 80 mg lovastatin) (Liu 2006). The recognition of the use of the fermented yeasted rice as a dietary aid, rather than classifying it as a drug, made the situation somewhat easier for those wishing to utilise the natural product. However, quality control has remained a problem (Gordon & Becker 2011).

10 Chinese medicines that utilise RYR have shown equally good clinical results. However, they contain a number of additional traditional herbs for heart disorders (see Liu 2006 for details). Side-effects from statin drugs include myalgia (muscle pain) and liver damage. 11 The market is significant: between 2005 and 2008 the market for RYR products expanded by 80% in the United States. Total sales in 2008 were around US$20 million (Adjari 2011).

The Oyster Mushroom (Pleurotus ostreatus) naturally contains quite high levels of lovastatin (2.8% dry weight) (Alarcon 2003). (Image courtesy Jean-Pol Grandmont, Belgium)

Other substrates have equally interesting medicinal potential in combination with Monascus yeast products: • Turmeric: anti-inflammatory, lipid-lowering and antioxidant activity was enhanced by the addition of turmeric, as well as increasing the phenolic and curcumoid contents. As a result the anti-atherosclerotic value of the product was also potentiated (Kuo 2009; Cheng 2009). • Ginger: a similar effect was seen with the addition of ginger, with increased production of 6-gingerol (Chen 2010). • Soybeans: Monascus-fermented soybean extracts (MFSE) enriched with natural statins (mevinolins) and isoflavones (daidzein, glycitein and genistein) have similar potent antihyperlipidaemic activity and antihypertensive potential (Pyo & Seong 2009; Pyo & Lee 2007). • Mineral-enriched ocean water (from depths over 200 metres): its use as a substrate showed reduced levels of the toxic by-product citrinin12 (Lee 2011). • Garlic: a clinical study using garlic fermented by Monascus pilosus demonstrated good results for lowering triglycerides and cholesterol, with suggestions for its use in the treatment 12 The mycotoxin citrinin, a red pigment, can be produced during Monascus fermentation. Processing strategies have been developed to favour selection for desirable hypolipidaemic agents, notably monascin and ankaflavin, which are yellow (Shui & Pan 2011; Jia 2010; Lin 2008).

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of metabolic syndrome (Higashikawa 2012; Kuo 2008; Sumioka 2006). • Ginseng: improvements in the amount and bioavailability of ginsenosides in Monascus-fermented red ginseng (Panax ginseng), as well as good amounts of monacolin K, suggest similar benefits for this type of processing (Hong 2011). Ginsenosides have cholesterol-lowering, blood sugar-regulating and antiischaemic effects – which were enhanced in Monascus-fermented red ginseng (with bifidobacteria). The product also showed protection against experimental ischaemic brain injury, suggesting benefits in conditions such as stroke (Trinh 2007; Bae 2004). Other studies have shown fermentation can improve the immunemodulatory, anti-allergenic, antiinflammatory and analgesic properties of ginseng products, with definite clinical benefits for the treatment of allergic rhinitis (Jung 2012, 2011; Lee 2012).

(Zheng 2010; Ho & Pan 2009; Hong 2011, 2008a, 2008b). This has led to the suggestion of its use as an adjunct chemopreventive or antineoplastic agent (Ho & Pan 2009). The orange pigments monascorubrin and rubropunctatin in Monascus have shown excellent anticancer activity, while monacolin K had a synergistic anticancer activity in combination with ankaflavin (Shi & Pan 2011). • There are also suggestions that the Monascusfermented Dioscorea can assist in the prevention of oral cancer, while Monascus fermented with dioscorea polysaccharide showed an inhibition of leukaemia proliferation (Lee 2012; Hsu & Pen 2012; Hsu 2011, 2010).

Recent investigations of RYR products have shown diverse additional potential health benefits: • The anti-inflammatory and antioxidant properties of Monascus-fermented rice has been suggested for use in treating alcoholic liver disease (Cheng & Pan 2011). • Metabolic problems: there are suggestions for the use of RYR in diabetes (Shi 2012, 2011; Shi & Pan 2010a, 2010b), as an anti-fatigue and anti-obesity remedy (Kim 2010; Chen 2008; Wang 2006). Mental function: interesting findings • regarding the potential of Monascusfermented products for mood disorders (depression), learning and memory, including age-related memory loss such as Alzheimer’s disease (Chuang 2011; Lee & Pan 2011; Lee 2008; Ou 2007). • Cancer: serious interest has been expressed in the product’s anticancer potential, notably in lung, prostate and colon cancer

Dioscorea batatas, from Ernst Gilg & Karl Schumann, Das Pflanzenreich Hausschatz des Wissens, 1900. Dioscorea batatas has been suggested for use as an adjunct to chemotherapy. Extracts contain a glycoprotein with potent immune supportive, antiinflammatory and antiallergic activities – as well as anticancer (anti-proliferation) properties in liver cells (Huong 2011; Jin 2011; Liu 2011; Su 2011; Oh & Lim 2009, 2008a, 2008b; Liu 2008; Lee & Lim 2008).

Anticancer Yams

Over the years there have been intriguing references to the deployment of various Yams for the treatment of cancer. A decoction of the Air-Potato Yam (Dioscorea bulbifera) was used for skin cancer by Aborigines of the Tully district in North Queensland (Webb 1959). This species contains polysaccharides with anticancer activity (Zhang 2007). There has also been a report of the Long Yam (Dioscorea transversa) being used as an

STEROIDS FROM YAMS

Dioscorea bulbifera vine in forest. (Courtesy Kim & Forest Starr, Hawaii)

adjunct in the treatment of post-surgical recovery of uterine cancer patients in Australia. Those receiving a remedy that included Long Yam had a speedier recovery (Kielczynski 1997). Other traditions support these recommendations. The Air-Potato Yam has been used in China for treating cancer of the thyroid, oesophagus and digestive tract – as well as for tuberculous lymphadenitis, haematemesis and haemoptysis. A tincture was regarded as being particularly useful for oesophageal, stomach and rectal cancer. The remedy was prepared by soaking Dioscorea tubers in 62 per cent spirit13 (Zhang 1989). In Bangladesh, Dioscorea bulbifera rhizomes were likewise recommended for tumours, as well as leprosy. Studies have verified anti-tumour promoting properties of rhizome extracts, with a number of flavonoids (including catechin) and the diterpene diosbulbin showing strong activity (Gao 2002). Other studies support the anticancer effects of diosbulbin B – as well as immunomodulatory properties (Wang 2012b) and anticancer activity in hepatitis A-infected liver cells14 (Yu 2004). In addition, various antibacterial diterpenes are present in Dioscorea bulbifera, some of which (including diosbulbins) attracted particular interest due to their activity against multidrug-resistant bacteria (Shriram 2008; Teponno 2006). Interestingly, a recent investigation that utilised Dioscorea bulbifera for the synthesis of antibacterial silver nanoparticles 13 Duke & Ayensu (1985) also mention the use of the plant for cervical cancer. 14 However, diosbulbin B has shown hepatotoxic potential (Xu 2011).

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Dioscorea bulbifera tuber (dried weight) contains saponins (5.77%), diosgenin (0.45%) and the diterpene diosbulbin. Sterol levels are quite high: around 189 mg sterol (per kg wet root) – containing cholesterol (2.2%), campesterol (22.6%), stigmasterol (46.7%) and β-sitosterol (28.5%) (Duke & Ayensu 1985). In addition, the tuber extract is rich in other compounds of pharmacological value: flavonoids, phenolics, reducing sugars, starch, ascorbic acid and citric acid (Ghosh 2012). (Image courtesy Paul Latham, flickr)

found a significant increase in the synergistic broadspectrum antimicrobial potency of the nanoparticles in combination with antibiotics (chloramphenicol, vancomycin, streptomycin) (Ghosh 2012b). There are diverse compounds in the Dioscorea genus with anticancer potential that support the traditional use of these herbs: • Cytotoxic saponins are present throughout the genus. Their mechanism of action is under investigation – for example, Dioscorea deltoidea var. orbiculata, D. panthaica and D. zingiberensis (Tong 2012; Shen 2002; Dong 2004, 2001). Deltonin from the latter has shown anticancer activity, while other saponins had anti-inflammatory and analgesic properties (Tong 2012; Ma 2011; Shu 2011). • Dioscorea collettii: extracts showed anticancer and cytotoxic potential. Protoneogracillin, gracillin, protoneodioscin and methyl protodioscin were isolated as the active anticancer components of D. collettii var. hypoglauca extracts (Wang 2006; Hu & Yao 2003, 2002, 2001; Hu 1996) • Dioscorea futschauensis: a prosapogenin of dioscin has shown anticancer (apoptosis-inducing) potential in leukaemia cells. Other components

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have apoptotic potential in colon cancer (Wang 2004, 2003; Liu 2003). • Dioscin and diosgenin: have cytotoxic properties against a number of cancer cell lines – including human colon carcinoma, osteosarcoma (bone cancer), leukaemia and erythroleukaemia cells (Miyoshi 2011; Wang 2002). Diosgenin can inhibit the growth of breast cancer cells (Tada 2009). • Dioscorea nipponica: extracts with an antimetastatic effect in oral cancer and melanoma cells show potential for use as a chemopreventive remedy (Chien 2012; Ho 2011). D. bulbifera, which has been included in a compound formulation15, shows good potential for treating oral cancer (Wang 2011b). • Dioscorea membranacea16 is a common anticancer ingredient in Thai herbal medicine. It contains cytotoxic naphthofuranoxepins (dioscorealides A and B) (Itharat 2003, 2004), while other components support immune system function. In particular, dioscorealide B has anticancer and antiinflammatory properties, as well as anti-allergic potential (Hiransai 2010; Tewtrakul & Itharat 2007, 2006; Tewtrakul 2006; Itharat 2004).

In Indonesia the fresh tuber of Dioscorea hispida was used for treating growths such as corns and calluses. Dioscorea esculenta (pictured here) tuber was similary used as a poultice on swellings and tumours (Hirschhorn 1983). (Image courtesy H Zell, Wikipedia) 15 The other ingredients were: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus arvensis and Dictamnus dasycarpus. 16 The Thai medicinal plants Dioscorea birmanica, Smilax glabra, Pygmaeopremna herbacea, Dioscorea membranacea and Smilax corbularia have been recommended for the treatment of cancer, septicaemia, lymphatic disorders and AIDS by traditional doctors. Studies of the inhibitory effects of these plants on the AIDS virus have provided good support for the use of Smilax corbularia and Dioscorea membranacea as antiviral agents (Tewtrakul & Itharat 2006).

Bat Plants and Black Lilies

Tacca leontopetaloides.

The genera Dioscorea (Dioscoreaceae) and Tacca (Taccaceae) have a fairly close botanical relationship – despite belonging to different families. Studies of the steroidal components of the Tacca genus have identified a number of constituents, some of them familiar, and others unique – of which several have intriguing pharmacological potential. Sapogenins (diosgenin and derivatives) were isolated from the leaves of the Australian Bat Plant, Tacca leontopetaloides. Extracts had a high molluscicidal activity that was linked to these components. Steroidal glycosides (including diosgenin and derivatives) were identified in the Sudanese species Tacca cheancer and T. chantrieri, and in a Vietnamese species (Abdel-Aziz 1990; Abdel-Aziz & Brain 1990). The genus contains different types of steroids (including withanolides), some of which have cytotoxic properties (Zhang 2009; Yokosuka & Mimaki 2007). More recently, the discovery of compounds known as taccalonolides rekindled interest in these herbs: notably Tacca plantaginea, T. chantrieri (syn. T. paxiana) and T. subflaellaea.17 17 This may, more correctly, refer to Tacca subflabellata (see ZY Wu & PH Raven (eds), 2000, Flora of China, Vol. 24, p. 274).

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These compounds have potential for the development of new anticancer drugs that have activity similar to the taxanes (Peng 2011; Muhlbauer 2010; Risinger & Mooberry 2010; Risinger 2008; Huang 2003; Tinley 2003; Chen 1997). Indeed, taccalonolides A and E are the first plant-derived microtubule-stabilising agents identified since the anticancer drug paclitaxel was isolated from the Pacific Yew (Liu 2006).

The Pacific Yew (Taxus brevifolia). Paclitaxel (taxol) has been used clinically for the treatment of lung, ovarian and breast cancer, cancer of the head and neck, and Kaposi’s sarcoma. Until synthesis was developed, the isolation of taxol from Pacific Yew bark was plagued by low yields – 1,200 kg bark = 28 kg crude extract, yielding only 10 g of the pure compound. Wild harvest of the bark kills the tree – a practice that lasted decades, from 1967 to 1993. This caused an environmental crisis threatening the survival of the species – until the fortuitous development of plant cell fermentation technology (see Goodman & Walsh 2001 for further details).

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Alternative Steroid Resources

The search for steroidal alkaloids from natural sources was a mammoth task that revealed their presence in a number of plant classifications. Although wild yams continued to be the best source of plant steroids, there were a couple of additional resources with practical commercial value, notably solasodine from the Solanum genus. Solasodine has properties similar to diosgenin, and is equally useful for corticosteroid drug manufacture. In addition, the genus Agave contains manogenin, gitogenin and hecogenin. The latter can be used as an alternative cortisone precursor and in Mexico Agave rigida was utilised for this purpose. Israel and China have also produced substantial amounts of hecogenin from natural sources. In China the following species were investigated as raw materials for steroid production: Agave amaniensis, A. americana, A. americana var. marginata, A. angustifolia, A. angustifolia var. marginata, A. dong, A. fourcroydes and A. sisalana – as well as some Agave hybrid species (Chen & Wu 1994). Even in 1978, a study of 34 species of Agave by Blunden and colleagues determined that the majority yielded steroidal saponins. Sisal (Agave sisalana) is a fibre-yielding plant that contains hecogenin and tigogenin at levels of around 10 per cent and 7 per cent, respectively, of the total sapogenin content. The crop has been cultivated in East Africa (Tanzania, Kenya) for drug production (Cripps & Blunden 1978). Glaxo Laboratories in Britain have even imported sisal waste as a raw material for cortisone production. Technological developments resulting in new Agave sisalana strains with higher steroid yields have made crop production a more viable alternative, in comparison to wild-harvested resources (Evans 2002).

Bales of sisal awaiting shipment. (Courtesy Wikimedia Commons, Public Domain)

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Agave sisalana was originally imported into Australia for both ornamental purposes and commercial hemp fibre production. Later, when cultivation was abandoned, the plant escaped into the wild and became naturalised in many areas. The specimen pictured here was happily propagating in bushland near National Park reserves on the Atherton Tablelands, North Queensland. Although they spread slowly, Agaves can form dense colonies that prevent the regeneration of native trees and shrubs. Little success in its eradication has been achieved by herbicide spraying – although the use of diesel as a carrier in the spray did improve the results. Application of the herbicide to the stump, or to the cut growing tip, enhanced its effectiveness considerably.

Other steroid resources include (Derwick 2006; Evans 2002): • Stigmasterol is found in Soybeans (Glycine max) and some other herbs. This compound, although it can be used for steroid synthesis, is not as easily utilised as diosgenin. • Sarsapogenin can be produced from Central American species of Yucca and Smilax. • Diosgenin is also present in Fenugreek, Trigonella foenum-graecum (India, Egypt and Morocco). The

Agave americana.

yield of Fenugreek seeds is fairly low: 0.8–2.2 per cent sapogenins, principally diosgenin and yamogenin. However, it is a fast-growing renewable crop that may be suitable for exploitation in some countries, particularly with the development of high-yielding strains (Evans 2002). • Diosgenin can be found in a number of other genera, albeit in quantities not of commercial value: Allium, Aspidistra, Balanites (B. roxburghii), Convallaria, Funkia, Ophiopogon (O. japonicus), Paris (P. polyphylla), Polygonatum, Smilax, Tribulus (T. terrestris) and Tamas (T. communis syn. Dioscorea communis) (see Singh & Kaushal 2007 for details). • Other diosgenin-containing species of interest include: Kallstroemia pubescens (tropical America, introduced to Brazil), Hechtia texensis (Central America) and various Trillium (North America) (Evans 2002).

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The Crepe Ginger (Costus speciosus) is a Southeast Asian and Indian species that contains diosgenin and tigogenin in the rhizomes. The starch-filled tubers have a substantial medicinal reputation in Ayurvedic traditions. It has been utilised as a febrifuge, as an antitussive (for coughing), a bitter digestive tonic (dyspepsia) and anthelmintic agent. Externally it was regarded as being useful for skin disorders and to treat snake bite. Plant extracts and saponins have significant anti-inflammatory and anti-arthritic properties – as well as substantial hormonal activity similar to that of stilboestrol. Interestingly, alkaloids from the plant have anticholinesterase activity with some similarities to physostigmine – which may be associated with the use of the plant for eye disorders and as a depurative (cleansing) agent (Satyavati 1976).

The Joshua Tree (Yucca brevifolia) contains sarsasapogenin that is suitable for steroid production. This plant, which is found in California’s Mojave Desert, contains high levels in the seeds (8–13%), which presents a renewable resource that would not harm the plant itself (Dewick 2002). (Image courtesy David Scriven)

Foxglove (Digitalis purpurea, top left), Climbing Oleander (Strophanthus gratus, top right) and (bottom) Silk Vine (Periploca graeca). There are some interesting chemical relationships associated with the steroidal saponin constituents of a number of plants that have been effectively used as cardioactive drugs. Gitogenin, which is the steroidal component of various Agave species, can also be extracted from Digitalis herbs (e.g. D. purpurea and D. lanata) – which have provided the famous medicines digitalis and digoxin. Sarmentogenin is a very similar compound to diosgenin that has been isolated from African species of Strophanthus (e.g. S. sarmentosus and other species) – vines that were once used as an infamous ‘ordeal poison’. They were, however, later valued as a source of the cardioactive drug strophanthin. The Russian Silk Vine (Periploca graeca), which has properties similar to digitalis, contains the cardioactive agent periplogenin. Interestingly, the African species Periploca nigrescens also contains strophanthidin. In addition, the genus Convallaria, source of Lily-of-theValley herb, contains cardioactive glycosides similar to Strophanthus, as well as steroidal saponins (Evans 2002).

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Fenugreek (Trigonella foenum-graecum), from Prof. Dr Otto Wilhelm Thomé, Flora von Deutschland, Österreich und der Schweiz, Gera, Germany, 1885.

Fenugreek seeds. Fenugreek’s value as a steroid resource may lie in its diverse uses – with potential as a multipurpose crop for oil, mucilage, flavouring extracts, and a high-protein fodder. The diosgenin yield can be increased by fermentation (similar to Dioscorea) although, because cheaper resources remain available, the herb has not achieved any great favour for commercial exploitation (Evans 2002).

Smilax aristolochiaefolia, from Franz Eugen Köhler, Köhler’s Medizinal-Pflanzen, 1887. The Sarsaparilla herbs from the Smilax genus (S. aristolochiaefolia, S. regelii, S. febrifuga) contain steroidal components (sarsasapogenin and smilagenin) that can be utilised for drug synthesis. Steroid levels in the roots, notably parillin, are around 1.8–2.4 per cent (Derwick 2002).

 The story of the search for alternative glycoalkaloid resources from the Solanaceae is a subject of immense importance. It not only involves a European steroid industry based on a couple of Australian Solanum species, but inspired a massive review of native Solanum species across the continent. Just as in the genus Dioscorea, many species of Solanum have extraordinary medicinal potential – antiinflammatory, cardiovascular, immunomodulatory, antimicrobial and antiviral properties being among the foremost of these. However, in recent years it has been the search for anticancer remedies that has truly thrust some of these herbs into the forefront of pharmacological and clinical investigation – with some remarkable success stories.

Chapter 12

KANGAROO APPLES AND BLACKBERRY NIGHTSHADES The Solanaceae family contains probably the greatest diversity of medicinal, edible and toxic plants in the world – with over 3000 species classified in around 84 genera. The Solanum genus is by far the largest, containing somewhere between 1,700 and 2,000 different species that exhibit a remarkable range of form (trees, shrubs, vines, small herbs) and habitat tolerance. In Australia there are around 186 species overall, 30 of which are naturalised. Many of the latter have a weedy habit, such as the introduced Black Nightshade (Solanum nigrum) and the American Nightshade (S. americanum). Others are shrubby rainforest pioneer plants or tropical ornamental vines.

Brazilian Nightshade (Solanum seaforthianum), of tropical South America, widely naturalised along the Queensland coast, ranging to New South Wales (and occasionally found in other mainland states).

Flowers of the Eggplant (Solanum melongena) and the Potato (S. tuberosum). (Image on left courtesy Bruce Allen)

Solanum rostratum (USA, Mexico) is naturalised in southern Queensland, New South Wales, Victoria, South Australia and Tasmania. (Image on right courtesy Kim & Forest Starr, Hawaii)

The Solanum genus is characterised by distinctive starry five-petalled flowers in a colour range that encompasses pure whites, brilliant blue hues, delicate lilacs and a remarkable vibrant rich purple. The

Brazilian Potato Tree (Solanum wrightii), a tropical American ornamental. 451

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blossom centre displays five prominent bright yellow anthers. Yellow-flowering species such as the Spiny Nightshade (Solanum rostratum) are less common – although in the closely related Lycopersicon genus, from which the Tomato is sourced, small yellow flowers are characteristic. Lycianthes is another closely related genus, a few of whose members have striking purple flowers and were formerly classified as Solanum. The genus Cyphomandra, from which the Tamarillo is sourced, has also been reclassified as Solanum. While the most familiar Solanum-sourced foods are the Eggplant and Potato, there are numerous species that yield smaller crops of edible fruit. Notably, the Australian ‘Bush Tomatoes’ have been a significant outback fruit resource.1

Top: The Flannel Bush (Solanum lasiophyllum) is a ‘Bush Tomato’ resource that is widespread throughout the arid regions of Western Australia and South Australia. A decoction of the roots has also been utilised as a poultice on leg ‘swellings’ (Isaacs 1994). Solanum quadriloculatum (bottom) shares a similar arid habitat, although it favours the central part of the continent (Northern Territory, northern Western Australia, South Australia, outback Queensland and New South Wales). This is a toxic species, which means the fruit are inedible, even when ripe. (Images courtesy Craig Nieminski) 1 This topic is discussed in detail in Volume 3.

Solasodine for Steroid Production

The Solanum genus, like Dioscorea (discussed in the previous chapter), is of particular commercial importance for steroid production. Numerous species contain solasodine, which (similar to diosgenin) provide raw materials for the manufacture of oral contraceptives and anti-inflammatory agents. In the mid-twentieth century two Australian species gained a significant measure of international fame – the Kangaroo Apples Solanum aviculare and S. laciniatum. These plants contain high levels of solasodine, particularly in the unripe berries – which are toxic, albeit they may be edible when ripe.2 When these and related species were discovered to be useful drug resources they were intensively researched in Russia and nearby Eastern European countries (Hungary, Bulgaria, Czechoslovakia, Poland and Romania), China, India, Egypt and New Zealand (Collins 1976). This resulted in extensive phytochemical reviews of the Solanum genus during the 1960s. Solasodine was already commercially produced by Russia and Hungary, and numerous candidates from around the globe were found to have potential for steroid production. Eligible plants included (Collins 1972): • Solanum incanum: Africa. • Solanum indicum (now S. lasiocarpum): the Indian Nightshade, which ranges from China, India and Indochina, to Malesia and the Solomon Islands. • Solanum trilobatum: India. • Solanum eleagnifolium: the Silver-leaf Nightshade from North and South America. This species has a noxious weed status in many places, including Australia3, Africa and the Mediterranean. • Solanum platanifolium (now S. mammosum): Nipplefruit. from South America, widely naturalised in Central America and the Caribbean. Found as an ornamental in Australia. • Solanum khasianum: India. • Solanum marginatum: North America. • Solanum paludosum, S. sessiliflorum and an unclassified Solanum species: Brazilian investigations 2 Although many ripe fruits of Solanaceous herbs are utilised as vegetables, there are species of Solanum whose ripe berries have substantial potential for disaster. For instance, one Indian study that examined 31 Solanum species, found 23 solanines that were, in some cases, present at high levels (up to 6.1% of the dry weight) (Frohne & Pfander 1984). 3 Naturalised in the southern half of the continent: Western Australia (southwest), South Australia, Victoria, New South Wales and Queensland (south).

KANGAROO APPLES AND BLACKBERRY NIGHTSHADES

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identified significant amounts of solasodine in their fruits (Barbosa-Filho 1991) However, it was found there could be substantial chemical variation between species. For instance, reports of high levels of solasodine in Solanum sisymbriifolium fruit (7.2%) led to initial evaluations that appeared to compare favourably with that of S. khasianum (5.2%) – a species that was regarded as a particularly rich resource. However, later analysis gave disappointing results, with the level of solasodine in Solanum sisymbriifolium considerably less than the original estimation (leaf 0.93%, stem 0.73%, berries 0.23%). Thus cultivation of the plant as a drug resource became an uneconomic prospect (Subramani 1989). Despite this, other compounds with pharmacological properties such as solamargine and β-solamarine were present (Bagalwa 2010). Root extracts were of particular interest as they demonstrated significant experimental hypotensive activity, with nuatigenin-3O-β-chacotriose showing good antihypertensive properties (Ibarrola 2011, 2000, 1996).

Solanum aviculare.

Solanum laciniatum.

The Viscid or Sticky Nightshade (Solanum sisymbriifolium) is a thorny species with a sticky characteristic. Native to South America, this herb is now considered an invasive weed in some countries, including South Africa, Japan and some Pacific Islands. In Australia, it is found in southern Queensland, New South Wales and Victoria. It is one of the species with molluscicidal properties that has attracted serious research interest – as have Solanum nigrum, S. nigrum var. villosum (S. villosum), S. lycocarpum and S. xanthocarpum. Molluscicidal (snail-killing) activity is important because snails are the intermediate hosts for many parasitic infections, including schistosomiasis (bilharzia) (see Table 12.4, page 484). (Courtesy Hubert Smietanka, Wikipedia)

Egg of the parasite Schistosoma mansoni, a source of the schistosomiasis infection. (Courtesy US Federal Government)

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A Weedy ‘Bitter Apple’

Solanum incanum is a weedy import that is found in the Calliope area of Queensland. Its native distribution is from sub-Saharan Africa and the Middle East, ranging to India. (Image courtesy Nepenthes, Wikimedia Commons, CC-by-SA 3.0 Unported)

The Bitter Apple (Solanum incanum) is so named due to its characteristically bitter qualities, although the leaves of less bitter cultivated varieties have been utilised as a vegetable. All parts of the plant contain solasodine, albeit the level can vary significantly, with smaller leaves having the highest concentration. While there is no current commercial use of this weedy plant, it is a prolific species that may well be a suitable candidate for steroid production. The fruit contains glycoalkaloids, mainly solasonine (as well as solasodine, solamargine, diosgenin, and yamogenin) and flavonoids (chlorogenic acid). However, the herb also contains the carcinogen dimethylnitrosamine – which appears to be linked with a high incidence of oesophageal cancer in parts of Africa where the sap is used to curdle milk (Matu 2008). Bitter Apple has a substantial medicinal reputation as an analgesic agent that has been utilised for numerous painful conditions (sore throat, toothache, stomach-ache, headache, angina, pleurisy, pneumonia, rheumatism, liver pain, menstrual pain) – with just about every part of the plant being deployed in some form or other: decoction (roots), infusion (leaves, plant), paste (leaf ), ash (burnt plant) or fresh applications (leaf sap, chewed root, pounded fruit). It has an equally good reputation for treating skin disorders (wounds, infections, whitlows, burns, sores, wounds, warts, skin growths, carbuncles), eye disorders

(conjunctivitis, ophthalmia, and the pain associated with ‘River Blindness’4) and venereal disease. Unsurprisingly, fruit extracts have strong antifungal properties, as well as a range of antibacterial activity (Matu 2008; see also Table 12.4). The fruit has been utilised as an arrow poison ingredient, and as a fish poison, in Africa. The fruit sap, mixed with butter, has been rubbed on cattle to kill ticks, and experiments tend to confirm its activity against Boophilus decoloratus5 (Matu 2008; Regassa 2000). 4 Onchocerciasis or ‘River Blindness’ is a distressing parasitic disorder due to filaria of Onchocerca volvulus that is characterised by severe inflammation and a highly irritant itching in the eye. 5 Euphorbia obovalifolia and Ficus brachypoda were shown to be the most effective anti-tick agents, reducing the tick burden in Ethiopian cattle by up to 70% (Regassa 2000).

Australian Kangaroo Apples In the 1970s, the commercial success of Australian species as a solasodine resource overseas provided inspiration for an in-depth survey of the native Solanum resources. The results were published in 1978 by Bradley and colleagues, who determined that 29 native species have an appreciable solasodine content. The evaluation was comprehensive, involving the collection of 85 species out of the total 94 representatives of the Solanum genus that had been identified at that time. Investigations confirmed that the highest solasodine levels were present in Kangaroo Apples (Solanum aviculare and S. laciniatum) and S. simile. Other useful species included Native Pepper (Solanum capsiciforme), Mountain Kangaroo Apple (S. linearifolium), S. symonii and S. vescum. A few species contained some additional alkaloids of interest: Solanum callium (isosolafloridine, solacallinidine), S. dunalianum (tomatidine, sola-dunalinidine) and S. dimorphispinum (tomatidine) (Bradley 1978). The wild Kangaroo Apples Solanum aviculare and S. laciniatum, which are difficult to tell apart, contain similar levels of solasonine. This can be used to produce solasodine, an anti-inflammatory and immunomodulating compound from which steroid drugs (cortisone and sex hormones) are manufactured.


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Table 12.1 Summary of Important Medicinal and Toxic Glycoalkaloids in Common Solanaceae

The steroidal alkaloids of the Solanaceae form the basis of most of their therapeutic and toxic potential. At least 90 unique steroidal alkaloids have been identified in over 350 Solanum species, with most of the glycoalkaloids belonging to the solanidane and spirosolane classes (see Milner 2011 for further details, including experimental anticancer properties as noted below). This table outlines the glycoalkaloids that are of particular interest in Solanaceae of culinary impoartance – tomato, potato and eggplant – as well as the medicinal Bittersweet and Nightshade herbs. Plant species Lycopersicon esculentum*

Solanum dulcamara Solanum melongena

Solanum nigrum and other ‘Blackberry Nightshades’

Solanum tuberosum*

Details of important glycoalkaloids (and aglycones: the steroid that is formed during metabolic processing in the plant) α-tomatine and dehydrotomatine are present in the tomato plant (aglycones: tomatidine is produced from α-tomatine, and tomatidenol from dehydrotomatine): tomato glycoalkaloids are relatively nontoxic and have shown anticancer properties. α-tomatine has shown anti cholesterol (cholesterol binding), antimetastatic and chemopreventive activity, and can be used as a starting point for steroid synthesis. Soladulcine B and β-soladulcine are important glycoalkaloids in Bittersweet herb Soladulcine B is also present in S. lyratum. α-solamargine and α-solasonine are the primary alkaloids in the Aubergine or Eggplant (aglycone: solasodine): these glycoalkaloids are relatively nontoxic, with highest concentration in the fruit flesh (negligible amounts in fruit skin), whereas in the majority of Solanum species high levels are found in the fruit peel or skin. Solamargine has substantial anticancer properties. Solasonine is reported to act synergistically with solamargine as an anticancer agent. In general, the Blackberry Nightshade group of Solanum contain solasodine as the primary alkaloid (derived from solasonine), with lower levels of solanidine. Solasodine (aglycone of α-solamargine and α-solasonine) is the primary toxic component of the green fruit of the Blackberry Nightshades, including Black Nightshade (Solanum nigrum). Solasodine has also shown potent anti-tumour activity and is utilised as a raw material for steroid production. α-solanine is present in high amounts in Black Nightshade herb; solanine is toxic (see below), although it has shown cytotoxic properties against human liver cancer cells. α-solanine and α-chaconine** are the main alkaloids in the potato plant (from which solanidine is formed). Both compounds are toxic and have anticancer activity; α-chaconine also has antimetastatic properties. Solanine has been used as an agricultural pesticide. High glycoalkaloid levels are found in green potatoes and the tuber sprouts, although significant variation occurs between varieties. Lethal dose 3–6 mg total glycoalkaloid per kg/bw (body weight); mild poisoning 1–5 mg/kg bw (Milner 2011). Toxicity: solanine poisoning includes symptoms of gastrointestinal distress (vomiting, nausea, diarrhoea), dizziness, headache, fever, sweating, loss of speech, tachycardia (fast heartbeat), mental confusion, hallucinations and dilation of the pupils. Severe symptoms involve convulsions, coma and death (Jain 2011).

* See also Volume 3. ** Solanine and ɑ-chaconine also have anti-cholesterol properties, but at a lower level of activity than tomatine (Milner 2011).

The humble Potato (Solanum tuberosum) may be utilised for the production of steroidal drugs. Dried and milled

potato vines and potato sprouts can contain appreciable amounts of solanidine, which is derived from solanine and chaconine in the plant (Nikolic 2005; Nikolic & Stankovic 2003). Potato tuber extracts have also shown analgesic and anti-inflammatory activity (Milner 2011) – as well as interesting mosquito larvicidal activity (Singha & Chandra 2011). Potato tubers have long been utilised as an antitumour remedy and were applied to growths, warts, callosities, corns and subcutaneous tumours – as well as being used for facial growths, throat cancer, carnosity (fleshy excrescence) of the eyes, and uterine cancer (Hartwell 1971). (Image courtesy Sanjay Acharya)

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The solasodine levels of the wild Kangaroo Apples are (Everist 1981): • Solanum aviculare: leaf 0.3–3.1 per cent and 1 per cent; stems 0.2–0.4 per cent; green fruits 1.7–3.5 per cent; ripe fruit 0.8–1.7 per cent. • Solanum laciniatum: leaf 1 per cent; stems 0.1 per cent; green fruit 0.3–3.5 per cent; ripe fruit 0.1–0.3 per cent

manufacture of Eastern European contraceptives. The Australian market was not so successful. While it was possible to supply solasodine commercially to overseas companies from Australia, attempts at local production failed due to management problems (Collins 1976). Despite the fact that the raw materials are readily available, Australia has continued to import the contraceptive pill.

Considerable natural variation in the steroid content could occur. The potential yield from naturally propagated plants was equally likely to be inconsistent – a problem that was overcome when strains suitable for commercial development were found. Cultivation of the Kangaroo Apple thus ultimately relied on cuttings sourced from high-yielding plants. Farming operations were set up in Europe and the crop adapted so successfully that for a long time these species provided the basic raw materials for the

Kangaroo Apple (Solanum aviculare) in Aboriginal medicine display, Garden of World Medicine, Chelsea Physic Gardens, Chelsea, London.

The Wild Tobacco (Solanum mauritianum, formerly S. auriculatum) is a pioneer species, originally from Argentina, which has become naturalised in the Australian rainforest. It is found along the eastern coastline from northern Queensland to New South Wales and Victoria, extending to South Australia. Solasodine is present in low levels in the leaves and stems (0.1–0.2%). Higher amounts can be found in the fruit (1.1%). South African folk healers used Wild Tobacco in the treatment of menstrual disorders, particularly for pain relief. This use appears to be supported by investigations that showed extracts could inhibit uterine muscle spasm (Lindsey 1999).


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Solanum aviculare and S. laciniatum, which are native to New Zealand as well as eastern Australia, are known as Poroporo, Poporo or Kohoho in New Zealand. These herbs gained a measure of fame as traditional remedies in Maori culture. They were utilised as antiinflammatory agents for treating skin problems (notably for the relief of itching) and rheumatic disorders. In an 1883 manuscript for a Maori Pharmacopoeia, J White recorded the following details:

The Felty Nightshade (Solanum densevestitum), with furry leaves and purple flowers, is a native species with a similar appearance to the ‘Wild Tobacco’. Although favouring a similar coastal habitat in northern New South Wales and southern Queensland, it is a smaller shrub with a somewhat different leaf shape. (Image courtesy Keith AW Williams, Native Plants of Queensland, Vol. 3)

A Maori Medicine

The leaf of this plant is applied by placing the underside of the leaf to the skin to cure itch. The leaves are also beaten into a pulp and applied as a poultice for old sores or ulcers. Also in cases where the itch has become sores the inner part of the bark is applied as a poultice to cure it. The leaves and young or tender parts of the branches are steamed in a Maori oven made by digging a hole and placing hot stones in the bottom, placing these leaves on the top of the hole till soft, then steeping these leaves and branches in oil. This oil is used to cure old wounds or sores.

FA Monckton information:

(1958)

provided

further

For skin eruptions like Maori pock where the papular eruption chafes into sores, especially around the joints, and when the intense irritation only starts when the patient comes out of the cold either to the bed or fireside, a strong decoction of the leaves of the New Zealand plant poroporo (which has a potatoe blossom and is called by the whites Bullabull) will, applied externally, effect a speedy cure. I have found it equally useful in other irritable skin eruptions where there is no insect [bite], but I dissolved sufficient carbol to prevent it fermenting and also added some boracic acid (quoted in Riley 1994).

Solanum aviculare.

The herbs were also incorporated into a complex preparation for treating bruising. Newspaper articles by Monckton regarding the ‘Maori itch’ described it as a disastrous contagion. The condition originated around 1867, at a time when there was a population explosion around the gold diggings. The name ‘Maori itch’ was adopted for want of

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a better term, although the condition was new to both the native Maori and the white settlers: ‘It chiefly affected the more clothed and consequently lower parts of the body, especially about the joints, or where there was most friction from the clothing or the seat and flaps of the saddle. Extreme cold produced comparative comfort but once you got before a fire or into bed the irritation prevented sleep and would drive you nearly frantic.’ The settlers appeared to suffer somewhat less than the Maori – with the inflamed patches limited to the elbows, inside of the knee, and areas exposed to friction from riding in a saddle. In many Maori individuals it advanced to form festering and running sores. The symptoms sound very much like scabies infection (see page 322, Chapter 7).

oxide of mercury and sapo mollis6 … It was years afterwards that I learnt that the nearest bush would have supplied me with a ready simple and effective remedy for application. There is a native shrub, with a potato blossom … It is non-poisonous, and a decoction made from the leaves and shoots is a bright, transparent, reddish-yellow liquid. It should be diluted until its application will not smart. It can be prevented [from] fermenting by adding one part of carbolic acid and glycerine to 80. I have some by me made years ago, and it remains good to the present day, only having lost its smell of fresh cut raw potato.

The herb also provided a useful hair shampoo. In contrast, a somewhat more unexpected recommendation was its use as a contraceptive by the Maori, taken just before the menstrual period (Riley 1994). 6 This is a type of soft soap prepared by heating olive oil with potassium hydroxide and water. It has also been known as Sapo Viridis or Green Soap, as it has a transparent yellow-green colour due to the olive oil component. Copper compounds or chlorophyll were occasionally added for colour enhancement.

The Feral Devil’s Fig

The main sites where the scabies mite causes irritation are highlighted in pink. It is a characteristic feature of mite infection that the pain is significantly worse at night, with intense itching. (Image courtesy CDC’s Division of Parasitic Diseases and Malaria)

Monckton found that effective treatment of the condition was extremely difficult: Eventually I did succeed in curing myself and a good many other persons by an application, the ingredient of which chiefly consisted of red

The unripe green fruit of many Solanum species are generally considered to be poisonous – although not all fruits are considered hazardous. The Devil’s Fig or Turkey Berry (Solanum torvum) is an introduced species with a small orange berry that is of culinary interest in Africa, India and Southeast Asia. Henry Burkill (1935) commented: ‘the yellow fruits are eaten in curries, in many parts of Malaysia; they are preferred unripe; make a very good flavouring; that they are poisonous seems to be [an] erroneous [belief ]’. The fruit also has an interesting medicinal reputation. Traditionally it has been recommended as an anti-diarrhoeal agent, a cough remedy, and used for pain relief. Moreover, the fruit (unripe or ripe) were said to have a strengthening or tonic effect that was particularly useful post-partum or for anaemia (Koffuor 2011; Sivapriya 2010; Muthu 2006). Devil’s Fig also has a good reputation as an antidiabetic remedy (see Table 12.4, page 483).


The Devil’s Fig (Solanum torvum), once thought to be an Australian native, was given the name S. longiflorum until its true identity was ascertained. The herb, which became particularly widespread in coastal Queensland, has a preference for areas of high rainfall, and has become a nuisance thorny weed. Many tropical countries classify it as a noxious invader that tends to colonise newly cleared land, creating impenetrable thickets and completely disrupting the natural ecology. Native to Central and South America (Mexico, Peru and Venezuela), the Antilles, West Indies and Bermuda, it has become a problematic weed in countries as widely separated as the United States (Florida), Papua New Guinea, Hawaii and the Pacific Islands. (Images of leaves and fruit courtesy Kim & Forest Starr, Hawaii)

In Malaysia, Solanum torvum fruit not only provided an aperitif and appetite stimulant, it was also utilised as an antihypertensive remedy (Zakaria & Mohd 1994) – a recommendation supported by recent studies showing that extracts had a blood pressurelowering effect in animals (Mohan 2009). In Sierra Leone, on the African west coast, the fruit decoction was taken as a cough medicine for children, while in India it was considered to be a useful remedy for an enlarged spleen. Devil’s Fig fruit, which contains sitosterol D-glucoside and carpesterol (0.04%), has

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shown anti-inflammatory properties comparable to hydrocortisone (Oliver-Bever 1986; Perry & Metzger 1981). A recent evaluation determined the Devil’s Fig (dried leaf extracts) had a 0.12 per cent total alkaloid content, which was comparable between Indian and Mexican sourced samples. However, in comparison to the Indian-grown herb, the glycoalkaloid level in Mexican samples was low (0.038%) – primarily composed of the solasodine derivatives solasonine and solamargine. Interestingly, the parent compound solasodine was only present in Mexican plant samples, demonstrating chemical variability in the species (Perez-Amador 2007). Prior investigations have established that solasonine levels of up to 1.0 per cent were present in the fruit, although this could vary, with the ripe fruit containing considerably less (i.e. 0.2%) (Oliver-Bever 1986; Everist 1981). This variation appears to be associated with occasional incidents of poisoning associated with the use of Jamaican ‘Susumber Berries’ (Solanum torvum) – with toxic and non-toxic varieties apparently being indistinguishable. A range of glycoalkaloids were present, including solasonine, and larger amounts of solamargine. Steroidal glycoalkaloid poisoning was associated with symptoms of substantial neurological dysfunction (dizziness, slurred speech, facial paralysis, ataxia, weakness), hypertension, confusion and gastrointestinal distress. A couple of severe cases required admission to intensive care with respiratory failure, requiring emergency ventilation (Smith 2008). However, the medicinal reputation of the plant has been substantiated by studies demonstrating that Solanum torvum (fruit) shows a wide spectrum of antimicrobial activity, as well as antiviral potential (Arthan 2002; Chah 2000). The antibacterial properties support the traditional use of the fruit juice in Cameroon for treating infections: abscesses, jigger (parasite) wounds, skin infections (ringworm, athlete’s foot), as well as skin problems in animals. It was particularly active against Streptococcus faecalis.7 In addition it was antifungal against a range of fungi, including the yeast Candida albicans (Chah 2000; Ajaiyeoba 1999). Interestingly, recent studies of the antibacterial activity of water-based fruit-coat extracts, 7 Extracts of Solanum macrocarpum have similar antimicrobial properties, with good activity against Bacillus subtilis and Streptococcus faecalis (Ajaiyeoba 1999).

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which had a high phenolic and flavonoid content, showed activity comparable to the commercial antibiotics chloramphenicol and streptomycin (Sivapriya 2010). In addition, isoflavonoids from this species have significant antiviral activity (Ndebia 2007). Solanum torvum leaves and root preparations have had an extensive medicinal reputation around the world: • Yucatan: the plant was said to possess narcotic, diuretic, sudorific and healing properties. It was recommended for treating convulsions, cough, asthma, gout, rheumatism, syphilis and skin diseases (Quisumbing 1951). • Papua New Guinea: Devil’s Fig was used to treat headaches and malaria.8 The juice was extracted from fresh fire-heated leaves and taken diluted in a cup of water (Holdsworth 1993). • Africa: in Ghana the herb was used as an antimalarial remedy (Asase 2010). • Africa: in Cameroon the leaf has been utilised as an analgesic and anti-inflammatory remedy, which has been supported by pharmacological studies confirming its activity. It also had a haemostatic reputation (Ndebia 2007). • India: leaf juice was used to reduce body heat (Muthu 2006), which also suggests its use for feverish conditions. • Fiji: the leaf liquid was employed for the treatment of gonorrhoea, and as a styptic agent to ‘stop bleeding’; a liquid extracted from pounded roots provided a remedy for tuberculosis and infected sores (Weiner 1985). • Philippines: the fresh leaves were poulticed on wounds and injuries (Quisumbing 1951), while the root decoction was taken by women after giving birth to reduce blood loss. Furthermore, it was considered to have antidotal properties for poisoning (Perry & Metzger 1981). • Malaysia: the pounded roots were applied to heal cracks in the feet (Perry & Metzger 1981). The 8 Steroids isolated from Solanum nudum have also shown anti-plasmodial activity, reducing the number of hepatic Plasmodium vivax trophozoites (Arango 2006; Londono 2006). The compound SN1 isolated from S. nudum has shown a synergistic effect with chloroquine and quinine (Pabon 2011). Other studies suggest that glycoalkaloids with chacotriose components (chaconine and solamargine) were more active than those with solatriose (solanine, solasodine), with chaconine being the most active for antimalarial activity (Chen 2010).

leaf also provided a remedy for giddiness and rheumatism (Zakaria & Mohd 1994). • Indonesia: the chopped root was steeped in distilled rice alcohol (arak) for two weeks, and the resultant tincture taken nightly to promote weight gain. It was ‘usually taken by slender young women who want to become more voluptuous’ (Leaman 1991).

Nipple Fruit (Solanum mammosum)

Nipple Fruit (Solanum mammosum).

The South American herb Solanum mammosum has gained fame as an ornamental due to its small breast-like fruit, from which it acquired the common names ‘Nipple Eggplant’, ‘Nipple Nightshade’ – and ‘Cow’s Udder’. The plant can be utilised for solasodine extraction – although other Solanum species are more suited to commercial production. The herb has been deployed as a cockroach poison, and also has a medicinal reputation. Central American remedies utilised the seeds for the treatment of colds, and the leaves for kidney problems. The


fruit tincture, boiled and the fumes inhaled, was used for the relief of sinusitis in Costa Rica, despite the steam having an irritant effect on the eyes. In El Salvador the roots were recognised as having diuretic and purgative properties, while in Mexico the leaf decoction was applied to cleanse wounds (Riley 1994; Quisumbing 1951). The Bolivian Mosetene Indians used Solanum mammosum fruit as a remedy for scabies – and it has shown moderate antimalarial activity in studies (Munoz 2000). Extracts have also shown anticancer (antiproliferative) properties against a range of cell lines, with indioside D (a furostanol glycoside) attracting particular interest (Wong 2008).

A Weedy Solasodine Resource

Solanum erianthum, from Francisco Manuel Blanco, Flora de Filipinas, Manila, 1880–83.

The Mullein or Velvet Nightshade (Solanum erianthum), also known as the Potato Tree, is a weedy species naturalised in many tropical countries that originates from the West Indies, Central America and Mexico. In Australia it is found along the coastline of the Northern

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Territory (Arnhem Land) and Queensland (Cape York to the Gold Coast), ranging into northern New South Wales. The fruit of this species has been responsible for cholinergic poisoning which involved symptoms of acute cerebrovascular disease (Huang 2009). The total alkaloid content of the leaf and fruit is around 0.4 per cent, although the solasodine content of Indian fruit samples was found to vary considerably (0.01–0.7%). Leaf samples from Vietnam contained solasodine (0.26%) and tomatidine (0.05%) – and in India the herb has been cultivated as a source of solasodine, yielding 40–50 kg/hectare. Diosgenin was also present in callus tissue samples of the plant. Despite its culinary use in India, in many places the fruit has been considered poisonous (with symptoms of nausea, headache, cramps) – and was even utilised as an arrow poison ingredient in tropical Asia (Modise & Mogotsi 2008). However, Solanum erianthum does have a number of medicinal uses. The leaves, which are considered to have significant diuretic properties, provided a cleansing agent, particularly for the treatment of leucorrhoea. They were also reputed to be abortifacient. Other leaf-based preparations have been recommended for haemorrhoids, scrofula (poultice), vertigo (decoction drunk), mouth sores (juice as mouthwash), stomach-ache (taken internally), rashes and sores (applied externally). The herb was used as an analgesic for treating headache (heated leaf applied locally), and to ease violent body pain (root decoction). The root (decoction) also has a reputation as being useful for gastrointestinal disorders: for the relief of digestive discomfort and to ease dysentery or diarrhoea – as well as for feverish conditions. The root bark, which is considered poisonous, has anti-inflammatory properties useful for treating arthritis (Blomqvist & Nguyen 1999). In South Africa a leaf decoction was recognised as having diuretic and purgative effects. It was taken as a cure for malaria, leprosy and venereal disease, and to stimulate liver function. Animal studies indicate that the

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leaf extract has a prophylactic effect against the malaria parasite, although it was not effective once the infection had developed. A flavonoidrich leaf extract has also shown antibacterial and antifungal properties against gram-positive bacteria, Aspergillus flavus and Candida albicans (Modise & Mogotsi 2008; Makinde 1987). The essential oil has substantial antibacterial effects – as well as cytotoxic activity in breast and prostate cancer cells (Essien 2012).

The leaf oil of Solanum erianthum is rich in α-terpinolene (18%), α-phellandrene (17.5%), p-cymene (16%) and β-pinene (12%) – while the fruit is humulene-rich (α-humulene 23%; humulene epoxide II 20%), with good amounts of caryophyllene oxide (16.5%), methyl salicylate (12%) and β-caryophyllene (11%) (Essien 2012). (Image courtesy JM Garg, India)

poisoning. Toxic reactions vary in severity, depending on the ripeness and amount of the fruit ingested, with symptoms of headache, vomiting, diarrhoea, hallucinations and coma (El-Ashaal 1999).

Black or Deadly Nightshade?

Black Nightshade (Solanum nigrum), from John Lindley, Medical and Economical Botany, Bradbury & Evans, London, 1849.

The Blackberry Nightshades

One of the most familiar members of the Solanum genus is a small weedy herb that is widely distributed throughout the world – the Black Nightshade (Solanum nigrum). In European and Asian traditions this plant has a surprisingly diverse medicinal reputation – and it can rate consideration as a commercial alkaloid resource due to its solasodine content. Tissue-cultured plants yielded the highest level of alkaloids (solasonine, solamargine and solanine) from the roots. This is not too surprising, as many Solanum species contain a greater complexity of root glycoalkaloids in comparison to the aerial parts. However, because substantial amounts of alkaloids are present in the fruit (whether ripe or unripe), they have been responsible for numerous incidents of

Berries of Solanum nigrum.

Solanum nigrum ‘Red Makoi’, a cultivar with edible red fruit. (Courtesy Vishal Sharma)


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The toxic reputation of Black Nightshade (Solanum nigrum) has long been a subject of debate. This may have resulted from the common name being confused with the Deadly Nightshade (Atropa belladonna), although the two plants are easily distinguished. Indeed, some older references quite erroneously refer to the Black Nightshade as the Deadly Nightshade, and say that it contains the same components (hyoscyamine, scopolamine and atropine) as Belladonna and Henbane (Hyoscyamus niger, confusingly known also as Stinking Nightshade or Black Henbane). Black Nightshade has a different glycoalkaloid profile, primarily based on solanine and related alkaloids9 – as does Bittersweet (Solanum dulcamara), which has also been mistakenly called ‘Deadly Nightshade’. Nonetheless, both Black Nightshade and bittersweet can have toxic potential.

Bittersweet (Solanum dulcamara), from Edward Hamilton, Flora Homoeopathica: Illustrations and descriptions of the Medicinal Plants used as Homoeopathic Remedies, Leath & Ross, St Paul’s Churchyard, Oxford St, London, 1852.

The berries of Solanum dulcamara have toxic potential similar to the Black Nightshade.

9 Solanine makes up around 95% of the total alkaloid component of Solanum nigrum, primarily as ɑ-solanine, although it readily hydrolyses to β- and y-solanine. However, solanine can be toxic even in small quantities (Jain 2011).

The Blackberry Nightshades, small white-flowered herbs, are a group within the Solanum genus (Section Solanum) with very similar botanical characteristics that can make it extremely difficult to distinguish between them. Various species have been easily confused, with differentiation made even harder when native species closely resembling introduced weeds are found in the same area. Originally it was thought that the majority of these herbs were a single species, the Black Nightshade (Solanum nigrum), but later refinements determined that the situation was much more complex, with the classification containing around 30 species – albeit only an experienced botanist could tell the difference between those that are more closely related (Mohy-uddin 2010). Around 12 species from this category are present in Australia – all but one, Solanum opacum, are introduced. The Blackberry Nightshades have toxic green berries, which become edible upon ripening and usually turn a dark purple-black colour. Green berries tend to cause gastrointestinal irritation, which does not occur when they ripen. The symptoms of

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poisoning can be variable and are probably influenced by the plant form or variety, as well as by growing conditions. The closely related herb, Bittersweet (Solanum dulcamara, Section Dulcamara), which is more easily distinguished by its petite purple flowers and red berries, can also be considered toxic.

similar to the spinach of Europe. I remember in the year 1852, during the rush of people to the Victorian goldfields, that persons coming from the Mauritius [Islands] often brought seed of this plant to grow for vegetables about their camp.’ Joseph Maiden also recorded the use of these ‘native currants’: ‘Mr. Agard Hagman informs me that these fruits are used for making jam in the [Richmond River] district. It requires comparatively little sugar in its preparation. They were also used for food by the prisoners at Norfolk Island in Mr. Backhouse’s time’ (Maiden 1900b).

Blackberry Nightshades in Australia

The most notable species in the Blackberry Nightshade classification are the common Black Nightshade (Solanum nigrum) and the American Nightshade (S. americanum). These white-flowered herbs favour similar habitats and are classified as weeds throughout the world. Their appearance is almost identical, making them almost indistinguishable, and the literature reflects this lack of discrimination. Although Solanum americanum has smaller flowers, they both produce small green berries that ripen to a glossy black.

The Black Nightshade (Solanum nigrum), despite its reputation as a weedy nuisance, is a highly underestimated and valuable medicinal herb. Even in the late 1800s FM Bailey noted that the Black-fruited Nightshade grew abundantly around Brisbane and was known by the children as the ‘Native Currant’. Two distinct forms were mentioned – the typical annual herb and a variety identified as Solanum nigrum var. humile. Of the latter he commented: ‘It is pretty generally allowed that the fruit of this form is unwholesome, yet the herbage of this and other forms of Solanum nigrum in the islands of Mauritius and Bourbon is highly prized as a culinary vegetable,

Solanum americanum in coastal habitat. (Images courtesy Kim & Forest Starr, Hawaii)


Black Nightshade (Solanum nigrum) and the American Nightshade (S. americanum) are widespread. Black Nightshade is found throughout the entire Australian continent, ranging from the coast to the arid regions of central Australia. The American Nightshade favours the eastern coastline (ranging inland) from Cape York to Victoria – albeit occasionally found in coastal regions of the other states. Overall there are 11 introduced species in the Blackberry Nightshade complex (Section Solanum), with many having a limited distribution. The other introduced species are: S. chenopodioides (S. chenopodinum is a different native species), S. douglasii, S. furcatum, S. nodiflorum10, S. physalifolium var. nitidibaccatum, S. radicans, S. retroflexum, S. sarrachoides and S. villosum. Only one native species belongs to this classification, the Green-berry Nightshade (Solanum opacum) – which was formerly thought to be various varieties of S. nigrum (var. chlorocarpum, var. humile, var. pterocaulon). It is a widely distributed herb that is found along the entire eastern coastline, throughout inland Victoria and New South Wales, extending to South Australia, Tasmania – and Papua New Guinea. The alkaloid profile of these herbs can be used to understand the botanical relationships between the species and their classification. An analysis of Solanum americanum, S. chenopodioides, S. nigrum, S. retroflexum and S. villosum showed that the principal glycoalkaloid was solasodine (67–86%) with much lower levels of solanidine (9–20%). Solasonine, ɑ-solanine and solamargine (ɑ- and/or β-) were also present in all these species (Mohy-ud-din 2010).

10 S. nodiflorum has attracted a fair amount of debate as some Australian authorities consider this species should be classified as S. americanum.

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Woolly Nightshade (Solanum villosum) is a weed found in a few places in northern Queensland, Adelaide (South Australia) and southwest Western Australia. (Courtesy Teun Spaans)

The numerous traditional recommendations associated with Blackberry Nightshades verify a long history of clinical use. These herbs have had extremely useful medicinal applications, although today their therapeutic reputation would be unfamiliar to most of us. Black Nightshade (Solanum nigrum), doubtless the most familiar, has long been utilised as a wound-healing agent and possesses effective antimicrobial activity, including broad-spectrum antibacterial properties. In Europe the fresh leaf poultice was applied locally to ease pain and reduce inflammation – an extremely versatile remedy that was employed for diverse skin disorders: boils, ulcers, burns, cancerous growths, eczema and pyoderma (infected eczema). The leaf juice has been variously utilised for treating ringworm, gout and earache, or as a gargle and mouthwash. The herb even had a reputation for being useful in the treatment of snake bite (Roberts 1990; Perry & Metzger 1981). A number of studies support this herb’s therapeutic reputation. In Ayurvedic medicine Black Nightshade was traditionally recommended for treating gastric ulcers – and studies have verified its ulcer-preventative and ulcer-healing properties. This was linked to an influence on secretory functions. Its use for the treatment of gastrointestinal (enteric) infections such as dysentery also suggested investigations into its potential against multi-drug resistant Salmonella typhi – against which it has shown moderate antibacterial activity (Jainu & Devi 2005; Rani & Khullar 2004; Akhtar & Munir 1989).

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Studies have indicated that a glycoprotein from Solanum nigrum has useful activity for the prevention of colitis (colonic inflammation) – a particularly distressing and painful condition (Joo 2009). There are a couple of related species with similar gastrointestinal potential. The Brazilian Solanum variabile and S. paniculatum have been utilised as folk medicines for digestive tract problems. The former had significant experimental preventive and curative effects on both duodenal and gastric ulceration. Root extracts of Solanum paniculatum were also found effective as an anti-ulcer agent with an anti-secretory effect (it reduced gastric acid secretion) (Antonio 2004; Mesia-Vela 2002). The Chinese Medicinal Herbs of Hong Kong (1984) mentions the use of a Black Nightshade tea as a febrifuge, anti-inflammatory and diuretic remedy. It was utilised for a remarkable array of inflammatory conditions and associated infections – respiratory disorders (chronic bronchitis), urinary tract infections, acute nephritis (kidney inflammation) and mastitis (inflammation of the breast). Traditionally, it was taken for feverish conditions (relieving heat), and was regarded as being useful for easing cough, as well as to remove phlegm congestion. Its diuretic effect was valued for reducing ‘swelling’ (oedema) (Kun 1985). There is also the suggestion of anti-histaminic activity of value for treating inflammatory and allergic skin reactions. The antioxidant, anti-inflammatory, antipyretic and analgesic (antinociceptive) properties of the herb have been confirmed experimentally (Milner 2011; Lomash 2010; Zakaria 2006, 2008; Reddy 1990).

Solanum americanum voucher specimen. This herb was formerly classified as Solanum nigrum or S. nigrum var. americanum. Many of the uses in Table 12.2 will also refer to the American Nightshade and, possibly, other varieties of S. nigrum. However, these plants can be extraordinarily difficult to tell apart – and, for medicinal and culinary purposes, would often have been used interchangeably. (Image courtesy Kim & Forest Starr, Hawaii)

The Chinese ‘Black Nightshade’ (Solanum photeinocarpum) has a similar medicinal reputation to S. nigrum. It has been recommended as a cooling febrifuge, while the marinated fruit was used to prepare a wine taken for asthma. The juice from the chewed leaf could ease throat infections – and it was used as a detoxicant to neutralise poisons. Decoctions of the plant have been taken to treat mastitis, stomach-ache and hernia, while a liquid (a simmered decoction) provided a wash for tinea infections (Chang 1989).

Table 12.2 Summary of the Medicinal Use of Solanum nigrum in Different Cultures Country China

Hong Kong, Chinese medicine

Southeast Asia

Preparation and medicinal use (reference) Duke & Ayensu (1985), Stuart (1911): • Leaf, root and stalk: cancerous sores, leucoderma (white skin patches), wounds. • Stem: young shoots used as potherb tonic for virility in men and dysmenorrhoea in women. • Plant: diuretic, febrifuge. Decoction applied to abscesses, cervical cancer, leucorrhoea (vaginal discharge), skin problems (dermatitis open sores), diarrhoea. Chinese Medicinal Herbs of Hong Kong, Vol. 3 (1984): Whole herb decoction (9–30 g herb): • Antipyretic: colds, fever, sore throat. • Infection and inflammation: chronic bronchitis, urinary tract infection, acute nephritis (kidney infection), mastitis (breast inflammation). • Anticancer: malignancies. • Externally: skin infection (boils, pyoderma), irritation and inflammation (impetigo, eczema), and as an antitoxic agent (snake bite). Perry & Metzger (1980): • China: leaves or shoots and seeds used medicinally; seeds have same property as young shoots; drug said to disperse congestion, prescribed especially for dysentery, sore throat, whitlow (nail infection).


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• Indochina: root expectorant, dried leaves evacuant, fruit laxative. • Indonesia: juice from ripe fruit used to cure sore eyes of hens. • Philippines: leaves applied to skin eruptions, also rubbed on depigmented areas of skin; tincture for relief of neuralgic pain. Southeast Asia

Malaysia, Southeast Asia

Oceania Papua New Guinea New Zealand

Hawaii

India

FAO, Rome (1984): Philippines: • Ripe fruit eaten raw; also made into jams and pies in rural areas; leaves and young shoots cooked and eaten as spinach-like vegetable. • Decoction of leaves: fomentation for various skin diseases, wounds, sore eyes; applied externally as a cooling agent and for vulnerary and vaginal irritation. • Fresh seeds: cosmetic use, rubbed on the cheeks to remove freckles and improve the complexion. • Valued as an antidiabetic remedy. Burkill (1935): • Vegetable: potherb; tender shoots boiled as spinach in India, Indochina, and throughout Malaysia. • Plant decoction: lotion for yaws; this use seems widespread in Malaysia, extending to Philippine Islands. • China: leaves, stalk and roots applied to wounds and sores; the young shoot used as a spinach and is considered to be a tonic. • India: berries and juice medicinal; plant considered beneficial when used as spinach; action is laxative and diuretic; juice may be applied in dropsy. Riley (1994): • Widely used as a tonic and for treating cancerous growths. • Popular healing remedy for wounds and sores. • New Zealand: ripe fruit eaten and used in jams; green leaves served as vegetable; ripe berries mixed with honey and taken for tuberculosis. • Samoa: ingredients in mixture for treating peritonitis; used for sunstroke with bark of the edible orange. • Tahiti: leaf juice (S. nigrum var. americanum): toothache. • Papua New Guinea: top leaves and stem cooked, and added to food for babies to stop diarrhoea; leaf sap placed on cuts. Riley (1994): • Highly respected herb in medicine and mythology. • Migraine, headache: treatment of very strong headache (migraine) with ‘dizziness affecting the eyes’, the berries are cooked with salt and the mixture squeezed into nose, which acted as a purgative. • Enema: 8 berries pounded and cooked with salt and soft bitter gourd. Mixture placed in shoots of Paper Mulberry (Broussonetia papyrifera syn. Morus papyrifera) for use. • Thrush infection: fruit given to infants. • Eye problems: coconut milk applied to eye and the herb also used as a wash; herb juice and salt put into eye to promote healing after cataract removal from eye. • Wounds: herb was used on perineal lacerations following childbirth. • Tonic properties: flowers given to babies; leaves eaten for debility. • Digestive tract tonic (shoots made into tea); digestive upset (leaves bruised and rubbed over abdomen); bloated stomach (young leaves eaten). • Respiratory tract disorders (asthma, lung congestion) or stomach cramps: leaves (also bark of roots and shoots) used in combination with other herbs; cough medicine, for colds, sore throat (leaf juice taken); colds (root chewed). • Sexual disorders (leaf added to mixtures); ‘womb troubles’: leaves mixed with Morinda citrifolia fruit and taken; young shoots mixed with Sida and coconut to treat womb collapse. • Healing and injuries: swollen tendons (leaf juice); sprains (leaves, stems, fruit); blisters on hands (leaves with salt made into paste). Kapoor (1993), Chopra (1956): • Herb: alterative, sedative, diaphoretic, diuretic, expectorant. • Liver and fluid retention: used as a vegetable or decoction in dropsy, enlargement of liver (hepatomegaly) and jaundice; chronic enlargement of liver (plant juice taken). • Inflammatory disorders: inflamed, irritated and painful body parts (plant decoction used as an anodyne wash); inflammation of kidneys, bladder and gonorrhoea (leaf juice taken). • Skin disorders: skin disease and psoriasis (young shoots); chronic skin problems (plant juice). • Miscellaneous: Blood spitting (haemoptysis), piles, dysentery (plant juice taken); fevers, diarrhoea, eye diseases, hydrophobia: berries considered alterative, tonic and diuretic. • Tamil Nadu: stomach-ache or stomach ulcer (fresh leaves cooked with onion bulbs and cumin seeds or the leaf juice taken); wounds or rabies (leaf paste applied directly as a healing agent); cough (whole plant taken) (Jain 2011). • Assam: asthma and whooping cough (root juice taken) (Parveen 2007). • Thar Desert: increase fertility in women (root decoction taken with sugar) (Sikdar & Dutta 2008).

468 Africa

South Africa

MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary anzania: ringworm (leaf paste applied topically); warts (leaf pounded and baked, used as dressing); children • T bed wetting (ripe fruits taken) (Moshi 2009). • Tunisia: erysipelas (acute streptococcal skin infection (sap used locally) (Leporatti & Ghedira 2009). • United Republic of Congo: snake bites or stings by venomous animals (whole plant macerated and applied) (Chifundera 1998). • Algeria: eye disorders including blindness, conjunctivitis, glaucoma, trachoma and cataract (diluted berry infusion); burns and skin infections (plant decoction) (Boulos 1998). Margaret Roberts (1990): • Respected traditional medicinal plant that has been used for centuries for a wide variety of ailments. • Vegetable: leaves cooked as spinach, considered to be blood cleansing, revitalising and energising, and can be cooked on their own or combined with other green herbs (nettle, amaranth species, purslane, sow’s thistle and fat hen). • Enema: used for abdominal ailments (leaf infusion); haemorrhoids, varicosities and bruises (leaves used as soothing application). • Respiratory disorders: ripe berries have a liquorice-like flavour and were steeped in brandy to make a gargle; ripe fruit crushed and mixed with honey as a gargle or used as a cough mixture for lung ailments including tuberculosis, for post-nasal drip, coughs and colds. • Skin problems, injuries: wounds, ulcers, infected rashes, scratches and bites (leaf infusion used as a wash); Xhosa and Zulu used leaf and green berry paste externally for wounds and ulcers; ringworm remedy used paste of unripe berry applied frequently to area; Xhosa used this as remedy for anthrax, and ringworm in dogs and children. • Excellent salve was made from Nastergal (S. nigrum) and Sow Thistle (Sonchus oleraceus) with lard or fat, applied to wounds and ulcers for cleansing and healing (recorded in 1772 by Thunberg). • Miscellaneous: Fruit used to treat heart conditions, liver ailments, eye diseases, tonic (infusion: 1 teasp fruit to ½ cup water, taken 2–4x daily); leaf tea: popular for fevers, malaria, convulsions, headaches, dysentery, diarrhoea, and as a sedative.

lack Nightshade for Environmental B Remediation?

Wild Black Nightshade herb (Solanum nigrum). (Image above courtesy Juni, Wikimedia Commons, CC-by-SA 2.0) The safe use of Solanum nigrum as a vegetable could well be linked to a detoxification effect during the cooking process – as well as variations in toxicity of the variety utilised (Jain 2011). An example is provided by Solanum scabrum (pictured), an edible African species classified in the Solanum nigrum (Blackberry Nightshade) complex – and formerly classified as the latter species. Solanum scabrum appears to have been farmed alongside S. nigrum, gradually resulting in the cultivation of intermediate plant forms suitable for use as a vegetable – in contrast to the more toxic varieties of S. nigrum found elsewhere (Olet 2005).

The fact that Black Nightshade will tolerate, even thrive, in a diversity of degraded environments accords the plant serious consideration for use in revegetation programs. While the herb’s weedy reputation has usually seen it


relegated to the category of a nuisance, there is some very interesting research on its remedial effects for heavy metal-contaminated soils. Solanum nigrum, along with Conyza canadensis (Horseweed) and Lobelia chinensis, can accumulate high concentrations of cadmium. Black Nightshade was found to be very tolerant of soils polluted with a combination of cadmium, lead, copper and zinc – common contaminants from industrial waste. In particular, the herb tends to accumulate arsenic (Ji 2011; Peng 2009, 2006; Wei 2010, 2006, 2004; Gisbert 2008). However, a number of factors were found to influence the plant’s concentration capacity for these metals: Salt could benefit plant growth by • counteracting the inhibitory effects of cadmium accumulation – in fact, the presence of salt enhanced accumulation11 (Xu 2010). The fact that salt exposure could benefit growth patterns has practical implications as increasing soil salinity is a worrying problem in many Australian environments. • Other compounds have demonstrated similar benefits on heavy metal uptake: iron-deficient soil conditions enhanced cadmium uptake, while proline pretreatment reduced stress to the plant and thereby improved the cadmium tolerance (Bao 2009; Xu 2009) • In the presence of zinc pollution, soil fungi (Glomus intraradices and G. claroideum) promoted uptake and accumulation – they enhanced zinc accumulation up to 49 per cent and 83 per cent, respectively (Marques 2008a, 2007, 2006). Cadmium-tolerant bacterial endophytes can similarly enhance bioremediation activity (Luo 2011). • Other strategies to enhance metal uptake in Black Nightshade have included the addition of EDTA (ethylene diamine tetraacetic acid), which substantially increased the concentration of zinc: up to 231 per cent in 11 Similar results were seen with Arabidopsis thaliana (Mouse-ear or Thale Cress), even at a low salt concentration (Xu 2010)

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the leaves, 93 per cent in the stems and 81 per cent in the roots. EDDS (S,S-ethylene diamine dissucinic acid) enhanced zinc accumulation in leaves, stems and roots: up to 140 per cent, 124 per cent and 104 per cent, respectively (Sun 2009; Marques 2008b). • Black Nightshade grows rapidly and there is the potential for two crops to be harvested on polluted sites annually – thereby substantially enhancing removal of soil contaminants.

Neurological Influences

A number of Solanum species have potent effects on nervous system function that appear to support many of their traditional uses. Since antiquity Solanum nigrum has been utilised as a sedative agent. Indeed, the Queensland Government botanist FM Bailey mentioned that Black Nightshade had a narcotic reputation, albeit not exceptionally potent: ‘the extract is said to possess the same power as lettuce opium [lactucarium; see page 470]. The leaves have been used with advantage in dropsical affections. Its action is diuretic and laxative’ (Bailey 1880). Black Nightshade has appreciable sedative, narcotic and emollient (mucilaginous) properties that have led to its use in many analgesic ointment formulations. The berry juice provided a painkilling remedy for toothache (a drop or two applied to the offending tooth) – although it was regarded as too poisonous to be regularly recommended for internal use. In Mexico the decocted fruit (a yellow liquid) was taken daily as a folk remedy for nervous conditions. This led researchers to investigate its neuropharmacological properties – which were found to be linked to a sedative effect on the central nervous system. The extract was without toxic side-effects (Perez 1998). The fruit contains acetylcholine (250 mcg/g fruit), which can influence nervous system function (de Melo 1978). Solanine (in the unripe fruit) is also considered to have analgesic and sedative properties and has been employed as an analgesic in migraine and gastralgia, as a nerve sedative in paralysis agitans, and for the treatment of chronic pruritus (itching skin conditions) (Oliver-Bever 1986).

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Latex from Lactuca virosa. Lactucarium is an interesting product from Lactuca virosa latex that was fancied to resemble opium and, therefore, utilised as a sedative and analgesic. It was reputed to have a mild euphoric effect, although this has been highly debated. Various other Lactuca species have been utilised as Lettuce Opium resources, including common lettuce (L. sativa) (Felter & Lloyd 1898). Experimentation with the making and use of ‘lettuce opium’ has (somewhat surprisingly) persisted to this day – with varied reports surfacing with regard to its euphoric value. However, Lactuca virosa does have poisonous properties, which can be quite serious. Some individuals have been admitted to intensive care for treatment after mistakenly utilising the wild herb as a vegetable (Besharat 2009).

Black Nightshade has been recommended for hydrophobia (tetanus) in Indian medicine – a condition characterised by increased excitability of the spinal cord that results in prolonged muscular spasms throughout the body. The seizures, which are extremely painful, are even provoked by minor stimuli. This infection has been known as ‘lockjaw’ because the initial symptoms are characterised by jaw stiffness that becomes an increasingly severe form of jaw spasm. The herb has also been used for the treatment of epilepsy in Nigeria. Studies of the anti-seizure potential of Black Nightshade leaf extracts showed an anticonvulsive activity that tends to support its traditional use (Wannang 2008). This may be linked to the herb’s solasodine component, as this compound possesses anticonvulsant and CNS depressant effects12 (Chauhan 2011). 12 In this study solasodine was isolated from the Sticky Nightshade (S. sisymbriifolium), which has also been utilised for treating disorders of the central nervous system (Chauhan 2011)

There are a few additional species with neurological potential. These include the Brazilian species Solanum paludosum. Root-bark extracts have exhibited a curare-like activity that was attributed to the alkaloidal components. Later studies demonstrated a vasorelaxant effect for an alkaloid fraction of the herb, which could be linked to hypotensive potential. Other components with neuropharmacological properties are present in the genus. For instance, examination of stembark extracts from Solanum pseudoquina revealed convulsive and excitatory activity. The active principle was identified as isosoalafloridine – a compound that also had antimicrobial properties (Monteiro 2012; Barbosa-Filho 1991; de Oliveira 1988). Solanum torvum seed extracts have shown interesting antidepressant potential (Momin & Mohan 2012).

A Bittersweet Herb

Decoction of Woody Nightshade, from Phillips’ Translation of the Pharmacopoeia Londonensis, 1841.

The old European physicians greatly valued Bittersweet (Solanum dulcamara) in medicine and surgery. The name Bittersweet originated


Dulcamara, from British Pharmacopoeia, 1867.

Bittersweet (Solanum dulcamara), from Heber W Youngken, Pharmaceutical Botany, 6th edition, P Blackiston’s Son & Co. Inc., Philadelphia, 1938.

from the old practice of chewing the green twigs – which initially had a nauseous bitter taste that later became sweet. This property is due to a chemical called dulcamarine. Closely related to Black Nightshade, this small European herb has a similar wound-healing and sedative reputation (Der Marderosian & Liberti 1988). The herbalist John Gerarde (1597) wrote of Bittersweet: ‘The juice is good for those that have fallen from high places, and have been thereby bruised or beaten, for it is thought to dissolve blood congealed or cluttered anywhere in the intrails [entrails] and to heale the hurt places’. The finely chopped leaves, made into a poultice, have provided a cellulite treatment, with ‘good results’ being reported. The herb has been used as a substitute for Sarsaparilla (Smilax

spp.) in skin disorders and as an alterative (blood-cleansing) agent. It is also useful for as an antiarthritic remedy, and its properties are listed as being diaphoretic, diuretic and narcotic (Kumar 2009). The American herbalist, Professor Harvey Wickes Felter (1922), noted that this plant was ‘a possible remedy in chronic skin diseases of a pustular, vesicular or scaly type, particularly the latter. It may also be tried in pundendal [vaginal] itching’. Somewhat more extreme was its recommendation for treating acute mania, nymphomania and satyriasis (excessive male sexual desire). The unripe fruit contains the alkaloid solanine, which has slight narcotic and analgesic properties (Kumar 2009; Oliver-Bever 1986). Solasodine has been isolated from the flowers, while β-solamarine13 is present in the roots. These alkaloids have all shown antibacterial activity against Escherichia coli and Staphylococcus aureus, although there was no significant activity against another common pathogen, Enterobacter aerogenes. Interestingly the three alkaloids, individually, showed better results than the standard drug streptomycin against S. aureus – with a longer duration of activity (Kumar 2009). Extracts of Solanum dulcamara (aerial parts) have also shown antibacterial activity against Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis (Turker & Usta 2008) – as well as anti-inflammatory properties (Tunon 1995). In addition, the herb contains the flavonoid kaempferol, which has shown male antifertility effects via alteration of sperm production and testicular function (Kumar 1989). Green Bittersweet berries are toxic, causing gastrointestinal distress and neurological problems. Ingestion results in burning of the throat, dilation of pupils, nausea and other symptoms of GIT irritation (anorexia, vomiting, constipation, diarrhoea). There may also be generalised problems such as muscular weakness, dizziness, drowsiness and convulsions. While poisoning is not usually fatal, death can 13 β-solamarine has also shown tumour inhibitory activity (Kupchan 1965).

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Anticancer Solanaceae

The use of Solanum for treating skin cancer, although controversial, appears to deserve continued clinical evaluation. Bittersweet has had a long history of use in treating skin growths ranging from warts to tumours, including warts or excrescences of the eyes, as well as a few other cancerous conditions. In Europe and the Americas all parts of the plant were utilised (leaf, leaf juice, root and bark). The herb poultice or ointment was of particular repute for the treatment of breast cancer (Hartwell 1971). Across the world, numerous other Solanum species provided anticancer folk medicines, usually applied locally for the treatment of tumorous growths (Riley 1994; Hartwell 1971; see also Table 8.1, page 355, for other anticancer Solanaceous herbs): In Australia, Bittersweet is found naturalised in Tasmania.

result from paralysis (Der Marderosian & Liberti 1988). An incident of solanine poisoning in a 4-year-old child, who presented as an acute cholinergic crisis at an emergency department in Chicago in the United States, is illustrative. The symptoms, although they appeared to be Belladonna (atropine) poisoning, were actually due to Bittersweet fruit toxicity. Physostigmine was deployed as an antidote (Ceha 1997).

Bittersweet, Woody Nightshade (Solanum dulcamara) contains interesting compounds called thermal hysteresis (antifreeze) proteins that act to reduce the freezing point of water. These proteins have been previously found in fish and terrestrial arthropods and, only relative recently, in plants. Those isolated from Bittersweet had a lower specific activity than those found in animals (Newton & Duman 2000; Duman 1994).

• Solanum atriplicifolium or Solanum frutescens (Argentina) • Solanum incanum (Africa) • Solanum melongena (West Indies, Venezuela and China) • Solanum nigrum (Indochina14 and the West Indies) • Solanum nodiflorum (Venezuela and French Guiana) • Solanum nigrum var. americanum (Colombia) • Solanum valdiviense and Solanum scolentum (Chile) • Solanum virginianum (American Indian) • Solanum racemosum (West Indies) • Solanum sisymbriifolium (Uruguay). An equally diverse number of species have been utilised as wound-healing, anti-inflammatory and antibacterial agents in the treatment of sores, ulceration, carbuncles, whitlows, herpes, leprosy and gangrenous ulcers. Solanum nigrum leaf preparations were mentioned as being a useful treatment for yaws (a serious bacterial infection of the skin, joints and bone due to Treponema pallidum pertenue15), swollen and painful testicles, as well as for ‘virulent gonorrhoea’ (due to Neisseria gonorrhoeae bacterium) – while the roots were said to have been employed as a remedy for bubonic plague (Riley 1994; Quisumbing 1951). In Africa, Black Nightshade was even utilised as a local application to anthrax pustules (Watt & BreyerBrandwijk 1962). 14 Floristically, the Indochinese region refers of a specific part of Southeast Asia. 15 This bacterium is closely related to the causative agent for syphilis (Treponema pallidum pallidum).


Nightshades for the Immune System

The ability to alter immune function, and antiinflammatory properties, are important clinical tools for the treatment of allergic reactions. Investigations of the immunomodulating properties of solasodine from Solanum nigrum identified an immune-depressive action (Oliver-Bever 1986), while the antihistaminic and antiallergic properties of berry extracts also support the use of this herb in the treatment of asthma and allergic disorders (Nirmal 2012). Solanum lyratum has shown strong antiinflammatory and anti-anaphylactic activity, with the potential to mediate the effects of severe allergic reactions (Zhang 2012; Lee 2001; Kim 1999; Kim & Lee 1998; Kang 1997). Other species with an effect on immune function include the Ethiopian Eggplant or ‘Garden Egg’ (Solanum aethiopicum), which has shown anti-inflammatory (anti-oedema) and anti-ulcer activity (Anosike 2012; Chioma 2011), while S. torvum has immunomodulatory and tonic properties (Koffuor 2011). Anti-inflammatory, antioxidant and immunomodulatory properties are also important for maintaining normal cellular function for the prevention of cancer.

A water extract of white Eggplant (Solanum melongena) has shown immunemodifying properties with good antiallergic potential (Lee 2001).

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Numerous investigations have been inspired by the traditional use of Blackberry Nightshades (notably Solanum dulcamara, S. nigrum, S. lyratum) as anticancer remedies. In particular, the Black Nightshade (ripe fruits and herb) has undergone extensive evaluation. Glycoalkaloids were the main focus of research, as solasodine derivatives (mono-, di- and tri-glycerides) have shown protective activity against skin cancer. Early evaluations of the anticancer components in Solanum nigrum identified the main cytotoxic compound as solamargine16 – which demonstrated potential in experimental lung cancer. Solamargine and solanine were able to induce apoptosis (programmed cell death), which is a valuable step in the restoration of normal cellular function and eradication of cancer cells. This led to clinical research into the use of glycoalkaloid extracts (solasonine, solamargine etc.) as skin cancer treatments.17 However, polysaccharides also appear to have an important role to play – showing substantial immunomodulatory and anticancer activity against cervical cancer in animal studies (Jain 2011; Li 2010a, 2010b; Ji 2008; An 2006, 2005; Wang & Lu 2005; Liang 2004; Son 2003; Kuo 2000). Numerous studies have continued to evaluate the mechanisms by which Solanum nigrum exerts its anticancer effects (Ding 2012; Kang 2011; Wang 2011a, 2010; Huang 2010). The anticancer potential of the plant appears to be a complex chemical affair with other active components playing a role. For instance, a glycoprotein with strong antioxidant properties has shown anticancer (apoptosis-inducing, cytotoxic), detoxicant and cholesterol-lowering activity (Li 2009, 2007; Lee & Lim 2008a, 2006a, 2006b; Lim 2005; Lee 2005, 2004a, 2004b; Heo & Lim 2005, 2004; Heo 2004). A strong polyphenolic extract of the ripe berries also exhibited anticancer potential in prostate and hepatocellular carcinoma cells (Nawab 2012; Yang 2010; Hsu 2009). In addition, a cancerpreventive (chemopreventive) peptide named lunasin, which has strong antioxidant and cellular protective properties, has been isolated from Solanum nigrum. This compound has also been found in soybeans, barley and wheat (Jeong 2010, 2007). 16 Solamargine is present in a number of medicinal Solanum species, including S. lyratum. Other alkaloids of interest in this species include strychnine, soladulcidine and glycoalkaloid A (Jia 2012). 17 Proposals have been made regarding the use of solasodine for innovative biochemical delivery methods for anti-cancer drugs.

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Clinically, the anticancer effects of Solanum nigrum have long been appreciated, particularly in cancers of the digestive tract. The whole herb has been a valued ingredient in Chinese cancer treatments, notably as a diuretic and toxin-removing agent (Zhang 1989). It was described by Chang (1992) as ‘one of the frequently used effective anticancer drugs’. It has entered into prescriptions for treating cancer of the throat, oesophagus, stomach, breast, lung, liver, ovary and bladder, as well as for brain tumours and soft tissue growths. Investigations continue to evaluate the herb and its glycoprotein components, particularly for clinical use in the treatment of liver and cervical cancer. The immunomodulating effects of the polysaccharide components18 have received particular attention (Hsu 2009; Li 2009, 2008a, 2008b, 2007; Lee & Lim 2008, 2006a, 2006b; Lin 2007).

White Nightshade

The White or Lyre-leaf Nightshade (Solanum lyratum) appears to have equally interesting potential – demonstrating experimental activity against a range of cancer cells lines (lung, cervical, hepatoma, colon adenocarcinoma and stomach carcinoma). This supports its clinical use as an anticancer agent, particularly in treatments for liver tumours (hepatoma), uterine, bladder and cervical cancer (Lee 2009; Hsu 2008; Liu 2008; Ren 2006; Shan 2002; Hsu 1990; Zhang 1989; Lu & Wang 1987). The Chinese Medical Dictionary recorded the traditional use of Solanum lyratum (Bai Ying) as an effective analgesic and diuretic indicated: ‘for oedema, migratory arthralgia, stranguria complicated by haematuria, lower abdominal pain related to qi, rheumatic arthralgia, abdominal pain due to ascariasis [worm infestation] in children, pain due to pus and blood in the ear’. Its analgesic properties, which are effective for pain relief in cancer patients, have seen the herb incorporated into many formulations, usually in combination with Black Nightshade. A popular treatment for stomach cancer utilised a prescription of Black Nightshade, White Nightshade, Chinese Sage (Salvia chinensis), Barbat Skullcap (Scutellaria 18 The anticancer properties of polysaccharides from a number of other valued medicinal plants have attracted similar interest: Platycodon grandiflorum, Cordyceps sinensis, Vernonia kotschyana, Panax notoginseng, Phellodendron amurense and Sparassis crispa (Li 2009).

barbata) and Mock Strawberry (Duchesnea indica). The herbs were boiled (decocted) and taken once daily (Chang 1992). Recent investigations of White Nightshade have indicated that it has significant immune-supportive properties. These appear to be associated with its anticancer effects, suggesting that the herb can have a chemopreventive role in the development of cancer, particularly gastric cancer19 (Liu 2011; Yang 2010). Extracts have shown activity against stomach cancer cells – as well as Helicobacter pylori. The latter suggests that the herb may also be useful in the clinical treatment of diverse gastric disorders. This not only supports its traditional use for treating cancer, particularly gastric cancer (adenocarcinoma, lymphoma) – but provide evidence that White Nightshade may be useful for other gastrointestinal disorders such as chronic gastritis, gastric and duodenal ulceration (Hsu 2010a; Wang 2009). Interestingly, Solanum torvum leaf extracts have shown similar potential against Helicobacter pylori and cellular-protective anti-ulcer properties, while the fruit had immunomodulatory activity (Koffuor 2011; Hsu 2010b; Nguelefack 2008).The antioxidant properties of White Nightshade may also be useful for preventing arteriosclerosis and associated cardiovascular disease (Kuo 2009). 19 Similar to S. nigrum, polysaccharide components may play a role in its activity (Yalin 2005).

Solanum lyratum berries and herb. (Images courtesy Dalgial, Wikimedia Commons, CC-bySA 3.0 Unported)


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Table 12.3 Traditional Chinese Medicine Anticancer Preparations Utilising Solanum nigrum This herb’s popular use for the treatment of traumatic injuries supports its anticancer reputation. The remedy acts to resolve swelling, reduce inflammation and alleviate blood stasis. Solanum lyratum has been incorporated into a number of prescriptions as a supportive analgesic agent (Chang 1992). In anticancer treatments the effect of Solanum nigrum can be enhanced by combination with Agrimonia pilosa (herb) and Sanguisorba officinalis (root). Combinations with Solanum lyratum (herb) and Duchesnea indica (herb) also form the basis of many anticancer prescriptions. Treatment Anticancer medicinal wine recipe

Preparation S. nigrum, S. lyratum, Duchesnea indica (Mock Strawberry), Salvia miltiorrhiza (Chinese or Red Sage): 30 g each; made into a medicinal wine with: Millett Wine (1.5 kg), Angelica sinensis (Dong Quai: 15 g root), Curcuma longa (Turmeric: 9 g root), toads (10). Epithelial tumour of urinary bladder S. nigrum herb with S. lyratum herb: 30 g each; decoction for oral administration, taken daily. Post-op chorioepithelioma S. nigrum herb 45 g, with Scutellaria barbata (Barbat Skullcap: 60 g herb) and Arnebia (a malignant fast-growing uterine euchroma (45 g root). tumour) Cancerous hydrothorax and ascites 500 g fresh herb decocted in water and taken daily. (fluid accumulation in the chest cavity and abdomen, respectively) Cancer of the liver S. nigrum (herb 60 g), with Ilecis (Ilecis folium 30 g): decoction taken daily. Note: Ilecis [sic] refers to Ilicis cornutae, the Chinese Holly (Ilex cornuta). Cervical cancer Decoction of herb either fresh (30–60 g) or dry (90–150 g), taken for a course of 15 days. S. nigrum condensed decoction prepared as a filtered tincture (alcohol removed and extract refined) for use as an injection. Fibrosarcoma (malignant tumour of S. nigrum herb (60–90 g) decoction taken daily. connective tissue of bone and muscle) Oesophageal cancer S. nigrum with S. lyratum (30 g each herb), with 15 g each of Oldenlandia diffusa (herb) and Scutellaria barbata (herb); prepared as a decoction and taken daily. Cancer of plica vocalis (vocal cord) S. nigrum with S. lyratum (30 g each herb), with 15 g of each of following: Duchesnea indica (herb), Salvia chinensis (herb) and Fagopyrum cymosum (Perennial Buckwheat root); prepared as a decoction and taken daily.

A Curative Anticancer Cream

Apple of Sodom (Solanum linnaeanum) is a thorny coastal shrub found in southern Queensland, New South Wales, Victoria, South Australia and Western Australia. It is one of a number of Solanum species that have been known by this name or as ‘Devil’s Apple’ – thus these common names should be used with care, ensuring the exact species is specified. (Images courtesy Kim & Forest Starr, Hawaii)

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Solanum linnaeanum (syns S. hermannii, S. sodomaeum) is an introduced weedy African plant that came to Australian shores in 1881. The herb had a good reputation in South Africa as an effective treatment for skin cancer, which inspired its widespread use – and its import to Australia by returning troops from the Boer War. Later, farmers reported that animals eating the plant (which, by then had acquired a weedy status) had a reduced incidence of skin cancers, notably cancer of the eye in Hereford cattle. The farmers themselves began using the fruit sap to treat sunspots on their hands. In 1987 a mixture of solasodine glycosides (solasonine, solamargine, diand monoglycosides, originally known as BEC) was extracted from the herb. Dr Bill Cham of Brisbane became interested in undertaking trials for treating skin cancer (squamous cell carcinoma) in cattle, horses and, ultimately, clinical applications for humans (Cham 2007; Cribb 1985b). The treatment of animals was highly successful. Remarkably, in many instances the cancer not only went into remission, its complete eradication occurred, with animals continuing to live out their normal life span (Cham 2008, 2007). This research resulted in the development of a flower-derived cream named Curaderm for the treatment of sunspots and skin cancers. Since then, the extraction process has changed and the cultivated Eggplant (Solanum melongena) has become a major source of the anticancer components. Clinical trials have shown that Curaderm is effective in a range of skin lesions and growths: keratoses (scaly skin due to cellular overgrowth that is potentially cancerous), keratoacanthoses (a form of fast growing skin cancer that may spontaneously resolve or turn invasive), and non-melanoma skin cancers – malignant skin tumours known as basal cell and squamous cell carcinomas (BCC and SCC respectively). BCC is a slow-growing tumour that tends to ulcerate and spread (a ‘rodent ulcer’), while SCC is usually a solar (UV) keratosis, although it can develop from skin ulcers, scar tissue or radiation (X-ray) damaged tissue. SCCs are serious and have deadly potential. Importantly, the use of Curaderm showed full resolution of the cancerous skin condition in all cases. It gave excellent cosmetic results, without scarring, and minimal side-effects. There is also a sunscreen product called Curasol (Cham 2007; Cham & Meares 1987). Unfortunately, in Australia there was an early

history of controversy over its use that resulted in bureaucratic restrictions that prevented its classification as an over-the-counter medication. However, Curaderm has been readily available over the internet, which allowed widespread use of the product. There is no doubt as to its efficacy in the majority of cases. However, despite its general popularity, there have also been confusing counter-claims with regard to the aggravation of some skin conditions. Importantly, as with the treatment of any disorder, proper diagnosis and professional advice is essential where there is any cause for concern. Despite the product’s good track record, there is always the possibility of inappropriate use or individual sensitivity. Until recently, proper double-blind trials have been lacking. This problem was addressed in a report on a product called Zycure (Curaderm, containing 0.005% solasodine glycoalkaloid mixture) for the treatment of basal cell carcinoma (Punjabi et al. 2008). The authors concluded: ‘We feel that this novel agent, Zycure, has overall efficacy, patient acceptance, low incidence of local adverse events and no systemic sideeffects. While surgery may remain a more appropriate treatment for many patients, we feel treatment with Zycure may prove advantageous if there are multiple small tumors of recent onset and perhaps in these patients where the location of the tumor makes other therapeutic approaches difficult.’ Ninety per cent of the treatment group maintained follow-up for a year, with 78 per cent of these individuals showing no recurrence of the condition. There is certainly a need for further good-quality product asessments and development. Future developments may well result in products that are suitable for internal use in a range of other cancers. Investigations into SRGs (solasodine rhamnosyl glycosides) have proposed injectable treatments for large solid tumours. Solbec Pharmaceuticals20 began trials of a product called Coramsine (previously known as BEC), which was proposed as a treatment of malignant mesothelioma (Cham 2008; van der Most 2006; Amalfi 2006). This is the cancer that results from asbestos exposure. Trials have also been planned for malignant skin melanoma and renal cell carcinoma (Amalfi 2006). 20 Solbec became Freedom Eye in 2008 – which, in turn, became FYI in 2010, which continues to market Curaderm.


Eggplant (Solanum melongena) fruit. The Eggplant contains a mixture of glycoalkaloids (BEC5) that form the basis of the anticancer cream Curaderm. An extremely low concentration of purified BEC5 (0.005% = 5 g eggplant fruit) is used in the cream formulation. However, because this is not the same as the glycoalkaloid mixture naturally present in the fruit, including Eggplant in the diet will not have an equivalent anticancer effect (Cham 2005; Jones & Fenwick 1981). The fruit also contains flavonoids with potent antioxidant properties. Of these, delphinidin (in the fruit peel) has shown experimental anticancer activity associated with an inhibition of fibrosarcoma tumour cells (Sudheesh 1999; Nagase 1998; Noda 1998). (Image courtesy Bruce Allen)

Unsurprisingly, studies of the Solanum genus suggest that other species possess useful anticancer properties. • Formosan Solanum species: a review of cytotoxic compounds focused on S. capsicastrum (rootbark) and S. indicum (fruit). The compounds capsimine, naringenin, capsicastrine and etioline21 had significant cytotoxic activity, while other components had strong liver-protective properties (Gan 1993; Chiang 1991). • Solanum incanum: extracts have cytotoxic and hepatoprotective properties. Carpesterol and β-sitosterol, isolated from the fresh berries, were identified as the liver-protective components. The anticancer alkaloid solamargine (as well as other steroids) was isolated from the herb and

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Solanum incanum is a wild species that is closely related to the Eggplant (S. melongena) and the Devil’s Apple (S. linnaeanum). This species not only contains the anticancer glycoalkaloid solamargine but a number of pharmacologically active saponins are also present (dioscin, protodioscin, methyl-protodioscin and indioside D) (Manase 2012). (Image courtesy Philipp Weigell)

fresh ripe fruit of this species, as well as from S. khasianum (ripe fruit)22 (Wu 2011; Liang 2004; Liu 2004; Kuo 2000; Hsu 1996; Fukuhara & Kubo 1991; Lin 1990, 1988; Chiu 1989). Solamargine exhibited potent cytotoxic activity against breast cancer cells and is a candidate for use in combination anticancer therapies (Shiu 2008, 2007). • Solanum sisymbriifolium (flower), S. amygdalifolius, S. chacoense (leaf ) and S. verbascifolium: extracts have experimental anticancer potential, with variable activity depending on the cell line studied. The latter was particularly active against human melanoma B16 line (Mamone 2011) – as were S. torvum root extracts (Arung 2009). • Solanum muricatum: extracts can induce apoptosis (Ren & Tang 1999). 21 Etioline has also been found in Solanum diphyllum and Lilium candidum. 22 Solamargine from this species has also shown antiparasitic activity against filarial worms (Ghosh 1994).

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• Solanum crinitum: Brazilian studies identified the flavonoid tiriloside and the glycoalkaloid solasonine as active anticancer (cytotoxic) compounds (Esteves-Souza 2002). • Solanum lycocarpum: extracts had significant antimutagenic activity against the chemotherapy drug doxorubicin (Tavares 2011) – as well as cytotoxic and anti-genotoxic properties (Vieira 2010). S. torvum has also shown a significant protective effect against doxorubicin nephrotoxicity in animal studies (Mohan 2010). • Solanum sodomaeum: studies have shown that steroidal glycosides had strong anti-leukaemic (antiproliferative) activity (Ono 2006).

Wolf Apple (Solanum lycocarpum) contains solasonine (6.6%), solamargine (4.6%), flavonols (0.04%) and polyphenols (3.6%). The herb, which is popular in Brazil, has antiepileptic, antispasmodic, sedative, blood sugar regulation, antioxidant and diuretic properties. It has also been utilised for the treatment of diabetes and obesity, and to reduce cholesterol levels (Tavares 2011). (Image courtesy Joao Medeiros, Wikipedia CC-by-SA 2.0)

The Jerusalem Cherry (Solanum pseudocapsicum) is naturalised in southern Queensland, New South Wales, Victoria, South Australia and Tasmania. Alkaloid extracts, particularly from the leaves, have substantial cytotoxic activity worthy of further investigation (Vijayan 2004; Badami 2003). (Image courtesy Kim & Forest Starr, Hawaii)

An Indian Anticancer Remedy

Solanum trilobatum. (Image © Edd Russell, San Jose, California, USA)


In Indian medicine Solanum trilobatum (roots, berries, flowers and/or herb) has been traditionally recommended for a variety of diseases – including respiratory distress (asthma), chronic feverish diseases, difficult parturition, cancer, kidney, heart and liver disorders (Nadkarni 1976). The herb has numerous pharmacological properties that support its traditional use: anti-inflammatory, analgesic, antidiabetic, antioxidant, hepatoprotective, anti-ulcer and antimicrobial. Recent studies have also shown that root extracts possess analgesic and anti-inflammatory activity (Pandurangan 2011; Ramakrishna 2010; Emmanuel 2006; Swapnalatha 2006). A range of glycoalkaloids are found in Solanum trilobatum, including ɑ-solamarine, solanine, solasodine, tomatidine and diosgenin23 (Vijaimohan 2010). Of particular interest has been the development of an anticancer product called Sobatum, which has shown antioxidant, antiinflammatory, cytotoxic and hepatoprotective activity, including experimental benefits for chemically-induced liver cancer. Sobatum has also demonstrated significant radiationprotective properties and a lack of toxic sideeffects in animal studies (Emmanuel 2006; Shahjahan 2005, 2004; Mohanan & Devi 1998, 1997, 1996; Mohanan 1996). Its protective effects extend to a reduction in toxic side-effects on heart and liver tissue that are associated with chronic lithium therapy – a drug that is utilised in the treatment of psychiatric disorders (Vijaimohan 2010). 23 The presence of diosgenin (and diosgenin glucuronides) in S. lyratum suggests this compound is potentially present in other Solanum species (Sun 2006).

The Medicinal Attributes of Plant Sterols Cholesterol is a natural precursor for steroid compounds in the body (sex hormones, corticosteroids). Very similar compounds are produced by plants (plant sterols or phytosterols) – with the most commonly encountered being campesterol, sitosterol (β-sitosterol) and

stigmasterol. Fungi produce ergosterol and brown algae contain fucosterol (Derwick 2002). In general, phytosterols are found in human tissues at concentrations 800–1000 times lower than that of cholesterol. Compared to cholesterol, plant sterols are less readily absorbed because they are bound to fibre. However, they are not particularly abundant in the modern diet due to the use of highly processed foods, a predominance of animal products, and a low intake of fresh fruit and vegetables. Plant oils contain high levels of phytosterols, while nuts and seeds contain moderate amounts. Lower phytosterol concentrations are found in fruits and vegetables. β-sitosterol, the primary phytosterol found in plants, appears to have rather remarkable pharmacological potential. It has shown a wide spectrum of activity – antibacterial, antifungal, antipyretic, anti-inflammatory and immunomodulatory attributes. Its potential for use as a supportive agent for immunological function includes an influence on diverse disorders such as stress-induced immune suppression, tuberculosis, chronic viral infections, allergies, cancer, rheumatoid arthritis and other autoimmune conditions. Furthermore, β-sitosterol has a diverse range of hormonal influences that can influence fertility, including antifertility and spermicidal activities. Significant beneficial effects have been seen on the prostate in clinical studies, and it has been investigated as an anticancer agent for prostate, breast and colon cancers – although studies remain inconclusive (Altern Med Rev 2000; Awad 2000a, 2000b, 2000c; Awad & Fink 2000; Klippel 1997; Malini & Vanithakumari 1990). Recent investigations also suggest that β-sitosterol has antioxidant and antidiabetic properties (Gupta 2011). The potential dietary benefits of phytosterols have attracted an enormous amount of research interest, mainly with regard to their cardioprotective and anticancer activity. Phytosterols have good antioxidant, radicalscavenging and anti-cholesterol attributes – effects that are complemented by various

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common dietary components – antioxidants, phytoestrogens, vitamins (B, C and E) and the carotenoids. The ability of sterols to effectively reduce the absorption of dietary cholesterol has led to the development of phytosterol-enriched foods such as margarines, salad dressings, orange juice, and even chocolate! Interestingly, the level of phytosterols found useful for lowering blood cholesterol may have a cancer-protective effect. However, studies have shown that the phytosterol component of the diet can vary dramatically between a Western-style diet (80 mg/day), a vegetarian diet (345 mg/day), and the Japanese diet (400 mg/day). The best natural resources are unrefined plant oils, seeds, nuts and legumes – although processing a plant oil will reduce its phytosterol component, and frying has an oxidising effect. Sterols have other potential dietary benefits. Soy-based products, rich in sterols and phytoestrogens, can be utilised as dairy and wheat substitutes with useful anti-allergic attributes24 (Fernandez & Vega-Lopez 2005; Ho & Pal 2005; Cicero 2004; Devaraj 2004; Hendriks 2003; Yoshida & Niki 2003; Davidson 2001; De Graaf 2001; Wong 2001; Awad 2000; Awad & Fink 2000). 24 Concentrated seaweed extract may contain extremely high levels of iodine, which leads to a cautionary tale of its use as an additive in soy milk. Bonsoy soy milk was withdrawn from the market throughout Australia due to extremely high iodine levels that resulted in clinical thyrotoxicosis (symptoms: palpitations, extreme fatigue, weight loss) – and, less commonly, hypothyroidism (usually in infants). Further investigation has shown that another dried seaweed product also had high levels of iodine. This level of exposure can be of particular concern in pregnant women due to the risk of foetal and neonatal hypothyroidism, with consequent developmental problems (www.health.gov.au/internet/main/publishing.nsf/Content/recallsoymilk, accessed July 2012).

Soya beans (Glycine max: 0.2% sterols in the seeds) contain sitosterol (50% total sterols), campesterol (20% total sterols) and stigmasterol (20% total sterols) at levels that are suitable for commercial extraction (Derwick 2002). (Image courtesy Antuco-Pandamon from Flickr)

Psyllium seed husks (Plantago ovata), which have been utilised as a water-retentive intestinal lubricant for conditions such as constipation, are a rich β-sitosterol resource (with lower levels of stigmasterol) (Nakamura 2005). (Image courtesy Bastique, Wikimedia Commons, CC-by-SA 3.0 Unported)

(Left) Sesame seeds (Sesamum indicum). The phytosterol content of sesame seeds and wheat germ was found to be quite high (400–413 mg/100 g), pistachio and sunflower kernels had mid-range levels (270–289 mg/100 g), while that of Brazil nuts was substantially lower (95 mg/100 g) (Phillips 2005). (Image courtesy ivcooking. com, Wikimedia Commons, Public Domain)


Aloe vera, gouache on vellum, from HansSimon Holtzbecker, Gottorfer Codex, 1649–59. Investigations have suggested that β-sitosterol from Aloe vera could have useful angiogenic effects on damaged blood vessels, supporting the body’s healing efforts after ischaemic injury (loss of blood supply to tissues) (Choi 2002). This would lend support to the traditional use of the herb as a mucilaginous healing agent.

More Medicinal Solanum

The Solanum genus has a wide range of medicinal prospects. These plants have been popular as remedies for innumerable conditions, many of which have utilised the anti-inflammatory and antibacterial properties of the genus for treating arthritis, gout, liver dysfunction, fevers, urinary tract dysfunction, skin disorders (eczema, psoriasis), and gastrointestinal problems (diarrhoea, dysentery). Individual herbs have been recommended for a multitude of other conditions, ranging from woundhealing to musculoskeletal problems, venereal disease and respiratory distress, as well as nervous system 25 This reference provides an extensive review of the folk uses of the Solanum genus.

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The Indian medical herb Kantakari (Solanum xanthocarpum), which has anti-inflammatory properties, contains solasodine in the berries. Leaf extracts possess significant wound-healing attributes (Dewangan 2012), as well as antidiabetic properties in animal studies. Lupeol (a triterpene) has been identified as a potent antioxidantcomponent (Gupta 2011a; Poongothai 2011). Lupeol also has significant experimental antiinflammatory properties, comparable to (but not the same as) indomethacin (Geetha & Varalakshmi 2001). In addition, male antifertility activity has been demonstrated, which suggests the herb has anti-androgenic properties (Gupta & Dixit 2002; Kanwar 1990; Dixit 1989; Bhargava 1988; Dixit & Gupta 1982). Solanum xanthocarpum has also shown hepatoprotective, antifungal, molluscicidal and mosquitocidal properties (see Table 12.4). (Image courtesy Arayilpdas, Wikimedia Commons, CC-by-SA 3.0 Unported)

dysfunction (Riley 199425). Diverse investigations have revealed a vast array of pharmaceutical potential for these plants: including antiviral, anti-allergic, anti-asthmatic, anti-parasitic, antimicrobial, anticholesterol, anticancer and calcium metabolismregulating activities. Glycoalkaloids (ɑ-solanine, ɑ-chaconine and tomatine), which often work in a synergistic manner to potentiate their effects, have well-documented antimicrobial properties as they are part of the plant’s chemical defence against pathogens (see Milner 2011 for further details).

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Table 12.4 Research into Medicinal Uses of the Solanum Genus Type of activity Antifungal agents

Anti-asthmatic remedies

Investigations Solanum aviculare Steroidal compounds can have interesting antimicrobial properties, for instance solamargine and solasodine from S. aviculare extracts have antifungal activity. Studies have shown this was enhanced by a combination of solasonine and solamargine due to a synergistic effect (Fewell & Roddick 1994; Rowan 1983).

Solanum chrysotrichum This herb has been traditionally utilised for the treatment of fungal infections in Mexico. A potent antifungal agent named SC-1 was isolated and found clinically effective for treating tinea pedis. A herbal extract was equally useful as an anti-dandruff (pityriasis capitis) treatment (HerreraArellano 2004, 2003; Alvarez 2001; Villarreal 1999; Lozoya 1992). Later studies established that other antifungal saponins in this species had similar potential with commercial prospects (Caspeta 2005; Zamilpa 2002). SC-2 was the most potent, with anti-Candida activity (fungicidal, fungistatic) against a number of strains of C. albicans, including drug-resistant strains, as well as other Candida spp. (Herrera-Arellano 2007). Subsequent clinical studies have shown good results for a refined herbal product, comparable to conventional treatment with ketoconazole, with further investigations undertaken to maximise its practical efficacy (HerreraArellano 2009a). Investigations of its potential use for other types of fungal skin infections (dermatophytoses) are underway (Herrera-Arellano 2009b). Note: S. chrysotrichum is naturalised in Queensland and New South Wales, primarily around the coastal border region of the Gold Coast, ranging to the Sunshine Coast. Solanum nigrescens Has a good reputation as a traditional remedy for fungal infections including vaginitis. Investigations of its antifungal activity against Candida albicans and Cryptococcus neoformans identified cantalasaponin-3 as the active principle (Caceres 1998, 1991; He 1994; Giron 1988). Note: Cantalasaponins were originally isolated from Agave cantala. The Guatemalan Sarsaparilla (Smilax regelii) has also demonstrated an anti-dermatophyte activity against skin fungi. Solanum xanthocarpum Has shown antifungal activity against Aspergillus, as well as possessing anti-inflammatory properties (Dabur 2004; Thenmozhi 1989). Carpesterol and other sterol glycosides from the herb showed antifungal properties (Singh 2007). Other species: Solanum hispidum: antimycotic saponins active against Trichophyton were isolated from the leaves (Gonzalez 2004). Solanum nigrum: investigations of antifungal compounds have led to the isolation of a protein with interesting antifungal activity that was active against plant pathogenic fungi: species of Fusarium, Colletotrichum, Macrophomina and Phytophthora (Campos 2008). Solanum niger: a study of medicinal plants employed in Hawaii as antimicrobial and antiinflammatory agents identified significant antifungal properties for extracts, albeit no activity was shown against Candida albicans or Aspergillus (Locher 1995). Solanum incanum: fruit extract had strong inhibitory effects against fungal pathogens (including yeasts and dermatophytes), as well as gram-positive and gram-negative bacteria and some pathogens of agricultural importance (Alamri & Moustafa 2012; Al-Fatimi 2007; Beaman-Mbaya 1976). A number of the Solanaceae have been utilised as anti-asthmatic remedies. Solanum xanthocarpum and S. trilobatum: Indian Siddha traditions employed these herbs for the treatment of respiratory disorders with studies confirming that extracts significantly benefited lung function. Clinically, progressive improvement was seen in the ventilatory function of asthmatics (measured by peak expiratory flow rate, PEFR) with a concurrent decrease in the symptoms of rhonchi, cough, breathlessness and sputum production. The results clearly indicated a bronchodilatory effect, associated with reduced swelling (oedema) and secretions in the airways. The action of the herbal remedy was rated equivalent to that of the bronchodilator deriphyllin (theophylline) although it was less than that of salbutamol (Govindan 2004, 1999; Jain 1984). Solanum americanum: In Hawaiian medicine the American Nightshade was used to treat asthma (Hope 1993). Solanum nigrum: Antihistaminic and anti-allergic actions of berry extracts have potential for use in the treatment of asthma and support its traditional use for this condition in Indian medicine (Nirmal 2012).


Antidiabetic properties

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Solanum torvum The Devil’s Fig has been utilised as an antidiabetic remedy in Brazil. Studies have shown antioxidant and antidiabetic activity. Methyl caffeate was isolated as the major antidiabetic component, which had substantial potential for clinical use (Gandhi 2011a, 2011b; Takahashi 2010). The antioxidant properties of the remedy were also linked to polyphenolic components that could reduce cellular stress in diabetic patients (Kusirisin 2009). Solanum xanthocarpum and S. muricatum (Pepino) Antidiabetic properties were linked to blood sugar regulatory, antioxidant, and anti-inflammatory activity (Hsu 2011; Poongothai 2011). Other species with traditional reputation as antidiabetic remedies include: Solanum nigrum and S. trilobatum, S. lycocarpum (Tavares 2011). Solanum surattense Recent studies have suggested that β-sitosterol has antioxidant and antidiabetic potential (Gupta 2011c). Protection of kidney and liver Solanum nigrum function Traditionally used for the treatment of genitourinary disorders, specifically to alleviate kidney and bladder pain. An examination of the remedy as a cytoprotective agent found that extracts (whole plant) had significant renal cellular-protective effects in a gentamycin-induced toxicity model. The benefits were associated with antioxidant properties of the herb (reducing free radical damage) (Prashanth Kumar 2001). Extracts have shown significant hepatoprotective effects in a number of forms of liver damage in animal studies. Clinically, leaf extracts were found useful for the treatment of cirrhosis of the liver. Their use could also assist in the prevention of serious side-effects associated with conventional drug use. The use of NSAIDs and various antibiotics (e.g. cephalosporins, amphotericin B, erythromycin, aminoglycoside antibiotics) can result in kidney damage. Liver damage is likewise associated with many drugs, chemical exposure, and excessive alcohol consumption (Hsieh 2008; Lin 2008; Raju 2003; Nadeem 1991a, 1991b). Fruit extract showed antioxidant and antihyperlipidaemic activity offering protective against ethanol-induced toxicity in animal studies (Arulmozhi 2010). Solanum lyratum Intraditional Chinese medicine the White Nightshade has a good clinical reputation for the treatment of liver dysfunction. It has been employed in hepatitis, inflammation of the gall bladder, and the early stages of liver cirrhosis. Its hepatoprotective action was attributed to scopoletin – a compound that has anti-inflammatory, antipyretic and analgesic attributes. The use of the herb for treating eczema would also appear to be linked to its scopoletin content – although other constituents (polysaccharides, flavonoids) can contribute to its overall activity. In addition, the herb has been utilised as an antibacterial agent for carbuncles and ‘toxic swellings’ (Qu 2005; Lin 2000, 1995; Kang 1998; Sultana 1995; Moundipa 1991; Hsu 1990). Note: Scopoletin has multitudinous pharmacological properties: anti-asthmatic, antiseptic, antitumour, central nervous system stimulant, cancer-preventive, hypoglycaemic (blood sugarlowering), hypotensive (reducing blood pressure), muscle relaxant and antispasmodic activity, as well as a uterine sedative action (Taylor 1998). Other species: Solanum xanthocarpum: hepatoprotective effects of fruit extracts shown against acute carbon tetrachloride toxicity in animal studies (Gupta 2011b). Insecticidal and antiparasitic Antiparasitic: leishmania, trypanosoma potential Solanum americanum: Antifungal and antiparasitic properties effective for the treatment of skin conditions. Many skin disorders have a parasitic component, particularly those contracted in the tropical regions of the world. Brazilian healers found American Nightshade useful for treating skin ulceration due to the Leishmania parasite. The herb has also shown antiprotozoal activity against the causative organism of Chagas disease (Trypanosoma cruzi) (Franca 1996). Anti-schistosomal: Solanum lycocarpum: schistosomicidal properties were linked to solamargine and solasonine (Miranda 2012). Solanum incanum: extracts have shown immune-stimulatory properties and anti-schistosomal activity (Mose 2011). Molluscicidal, mosquito larvicidal: Solanum nigrum: molluscicidal activity against a number of snail hosts, and could also kill the liver fluke parasite Fasciola hepatica. Comparisons of leaf, ripe and unripe (green) fruit determined that the latter was the most effective. Black Nightshade has demonstrated antiparasitic activity against Schistosoma mansoni, significantly reducing the infection burden in the snail host.

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MEDICINAL PLANTS IN AUSTRALIA Volume 4 An Antipodean Apothecary S. nigrum (black fruit) was more toxic than either S. nigrum var. villosum (yellow fruit) and S. nigrum var. juidaicum (red fruit) (Hammami 2011; Hammami & Ayadi 2008; Ahmed & Rifaat 2005; El-Ansary 2003, 2000; Ahmed 2001; Ahmed & Ramzy 1998, 1987). S. nigrum leaf extracts have also shown good molluscicidal properties (El-Sherbini 2009). Black Nightshade extracts possess larvicidal properties against mosquito larvae, some species of which are vectors for disorders such as filariasis, malaria, dengue fever etc. (Rawani 2010; Raghavendra 2009, Rahuman 2009, Ahmed 2001). Molluscicidal, mosquito larvicidal: Solanum xanthocarpum: investigation of molluscicidal activity identified α-solamargine as highly effective against Oncomelania snails (Li 2005). Fruit extract also had mosquitocidal properties against the vector for dengue fever in India. The extract was biodegradable, demonstrating ecologically friendly potential (Mahesh Kumar 2012a, 2012b). Other studies have confirmed molluscicidal and mosquito larvicidal properties for plant and fruit extracts; with methanol extracts of the fruit and seeds showing higher larvicidal activity (Changbunjoing 2010; Mohan 2010, 2007, 2005; Bansal 2009a, 2009b; Wei 2002). Other species with molluscicidal properties: Solanum aculeastrum: fresh root bark and berry extracts molluscicidal; berry extracts had more potent activity (Wanyonyi 2003); as well as a broad range of antimicrobial properties (Milner 2011). Solanum aculeatum: berry extracts had potent activity superior to S. incanum or S. nigrum (Mkoji 1989). Brazilian spp.: Solanum asperum, S. diamantinensis, S. paludosum, S. sisymbriifolium and S. stipulaceum have shown molluscicidal properties (Bagalwa 2010; Silva 2005). Solanum sodomaeum (leaves) and S. elaeagnifolium (berries): glycoalkaloid extracts (Bekkouche 2000). Solanum mammosum: α-solasonine and α-solamargine demonstrated potent molluscicidal properties (Alzerreca & Hart 1982). Other species with mosquitocidal activity: Solanum torvum: larvicidal activity of leaf and seed extracts (Kamaraj 2009, 2010). Solanum villosum: mosquito larvicidal and antimicrobial activity of mature leaf extracts (Chowdhury 2008a, 2008b). Solanum trilobatum: leaf extract had mosquito deterrent activity (Rajikumar & Jebanesan 2005).

healing reputation in Mexico for fungal disorders and inflammatory conditions. In Central and South America a leaf decoction of the American Nightshade (Solanum americanum) was utilised for treating skin fungi and gynaecological infections (leucorrhoea, vaginitis) – as was the related species S. nigrescens. In Guatemala the antibacterial properties of the latter were useful for respiratory disorders. It was also a valued folk medicine for fungal infections (He 1994; Giron 1988). (Image courtesy Efren Alvarez, flickr)

Anti-Herpes Solanaceae

Solanum nigrescens. Traditional remedies have effectively harnessed the antimicrobial properties of numerous Solanaceous herbs – a few of which have inspired investigations that confirm various Solanum species may have potential for commercial development. Of particular interest is the fact that a number of species possess effective antifungal activity. Solanum chrysotrichum has been the subject of intensive investigations based on its traditional

A number of Solanum species have antiviral properties with practical medicinal potential. Antiviral actions against Herpes simplex were demonstrated by various Solanum-sourced steroidal glycosides (Ikeda 2000). They include solamargine and solasonine (extracted from Solanum americanum) which provided the basis of a cream formulation utilised in a small clinical study. Excellent results were seen with its use in 90 patients infected with Herpes


Solanum americanum. (Courtesy Kim & Forest Starr, Hawaii)

zoster, H. simplex or H. genitalis. The success rate was high, with around 90 per cent of the infected patients showing no recurrence of their condition after 12 months of treatment. The remaining 10 per cent had the reappearance of their infection delayed (Chataing 1998). Recent investigations support the antiviral properties of Solanum torvum against Herpes simplex type-1 (Arthan 2002); S. nigrum seed extract against Hepatitis C (Javed 2011); and S. erianthum against Hepatitis B. Three different compounds from the latter showed good activity: a flavone, solamargine (glycoalkaloid) and ɑ-linolenic acid (unsaturated fatty acid) (Chou 2012). Solanum paniculatum showed activity against Herpes virus type 1, but not encephalomyocarditis or vaccinia viruses (Valadares 2009).

Cardioactive Alkaloids

Interestingly, a number of Solanum species have cardioactive properties, notably hypotensive potential: S. marginatum, S. distichum (S. indicum subsp. distichum), S. sisymbriifolium and S. giganteum. Solanogantine, isolated from Solanum giganteum, had hypotensive and spasmolytic activity that resulted in vasodilation (dilation of blood vessels) (Abdel-Aziz 2011; Ibarrola 2011; Gomes 1988). This is probably

Green Eggplant fruit. Glycoalkaloids in tomatoes and potatoes, such as tomatine and β-chaconine, have demonstrated a cardiotonic action on heart function (Bergers & Alink 1980; Nishie 1976). Interestingly, an extract prepared from the fresh berries of the green Eggplant have shown a significant hypotensive effect. Eggplant fruit was traditionally regarded as a useful diuretic and cholagogue (bile-normalising agent) (Shum & Chiu 1991). (Image courtesy Kok Robin at Aziatische-ingredienten.nl)

due to the presence of glycoalkaloids. However, when injected, various alkaloids demonstrated toxic potential – with effects similar to those of the cardioactive substance k-strophanthoside, a cardioactive glycoside from the African arrow poison Strophanthus kombe (and related species; see also page 449) (Shum & Chiu 1991). There has been a suggestion that some steroidal alkaloids in the Nightshade family resemble those found in the Veratrum genus (Melianthaceae) – which has suggested other avenues of investigation into Solanaceae alkaloids as cardioactive agents. However, their practical value may be limited. Veratrum alkaloids are well-known toxins.26 They affect the cardiovascular system, causing bradycardia (slowing of the heartbeat) and hypotension, as well as respiratory depression. 26 There are over 200 different veratrum alkaloids, with a compound called veratrine being the major focus of toxicological concern. It contains veratridine and cevadine as the main alkaloidal components (Schep 2006).

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Solanum marginatum, native to Ethiopia, is naturalised in South Australia, Tasmania and possibly Victoria. Extracts of this species can induce bradycardia (slowing the heartbeat) of a ‘veratrumlike’ nature (Vidrio 1988). (Image courtesy Leif & Anita Stridval, Wikimedia Commons, CC-by-SA 3.0 Unported)

While they were formerly utilised as hypotensive agents, the therapeutic index is very narrow, which means that the effective dose is very close to toxic levels. Thus the clinical use of veratrum alkaloids is dose-limited and can easily result in side-effects. Acute symptoms of veratrum poisoning include gastrointestinal distress (nausea, vomiting, diarrhoea, abdominal pain), as well as neurological dysfunction (paraesthesia, numbness, headache), muscle weakness, collapse and, occasionally, seizures (Schep 2006). As an aside, the name ‘Hellebore’ has been applied to various toxic plants in the genera Veratrum and Helleborus that are no longer utilised in medicine or herbal practice – although they remain in ornamental cultivation. However, some confusion in identification has occurred due to the similarity of their common names: White Hellebore (Veratrum album), Foetid Hellebore (Helleborus foetidus), Black Hellebore (Helleborus niger), Black False Hellebore (Veratrum nigrum) and Green Hellebore (Helleborus viridis). All of these plants contain toxic alkaloids, those in Helleborus (helleborin, hellebrin and helleborein) differing somewhat from the veratrum alkaloids.

Black False Hellebore (Veratrum nigrum). (Courtesy Agnieszka Kwiecień, CC-by-SA 3.0 Unported)

Decoction of White Hellebore, from Phillips’ Translation of the Pharmacopoeia of the Royal College of Physicians of London, 1836.


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Poison Cestrums, Calcium and Vitamin D

Jessamine or Red Cestrum (Cestrum elegans) is a Mexican native that is a garden escapee in southeast Queensland and Victoria. (Courtesy Philipp Weigell, Wikimedia Commons, CC-by-SA 3.0 Unported) Black Hellebore (Helleborus niger), from Prof. Dr Otto Wilhelm Thomé, Flora von Deutschland, Österreich und der Schweiz, Gera, Germany, 1885. According to the British Pharmaceutical Codex of 1934, Black Hellebore was: ‘a powerful hydragogue cathartic and emmenagogue. It is poisonous in large doses, producing violent inflammation of the gastric and intestinal mucous membranes. Applied locally, the fresh root is violently irritant’.

The poisonous European White Hellebore (Veratrum album) favours a similar alpine habitat to Gentian (Gentiana lutea) – and has been mistaken for the latter herb, which is wild-harvested for use as a bitter digestive tonic.

Early Jessamine or Red Cestrum (Cestrum fasciculatum) is a native of Mexico that is found naturalised in New South Wales and Tasmania (northwest).

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Night-blooming Cestrum (Cestrum nocturnum), from Francisco Manuel Blanco, Flora de Filipinas, Manila, 1880– 83. This species originates in tropical America and the West Indies.

Flowers of the Night-blooming Cestrum. (Courtesy Asit K Ghosh, Wikimedia Commons, CC-by-SA 3.0 Unported)

One other Solanaceae genus, Cestrum, is of considerable medicinal and toxicological importance. A number of introduced species can be found in Australia, both ornamental and weedy. Among those those classified as weeds are Jessamine (Cestrum elegans), Early Cestrum (C. fasciculatum), Orange Cestrum (C. aurantiacum), the Night-blooming

Jessamine (C. nocturnum) and the Green Cestrum (C. parqui). The latter has become so prolific along the east coast that it has been declared a noxious weed, in New South Wales, Victoria and Queensland (Lazarides 1997). All the Jessamines (Cestrum species) contain steroidal saponins at levels that can be potentially dangerous – a number of species are well known for being toxic to stock (goats, sheep, cattle). In the garden, children are attracted by the rich-looking toxic berries, although other parts of these plants have similar harmful potential. The purple-black fruit of Green Cestrum (Cestrum parqui) are regarded as particularly toxic, earning this shrub the title ‘Green Poisonberry’, and it has long been associated with animal poisoning (cattle, poultry). The Nightblooming Jessamine (Cestrum nocturnum) has been similarly implicated in cases of poisoning in children and pets – as has the Day Jessamine (Cestrum diurnum). The symptoms described in a case report of a poisoned child resembled atropine poisoning – muscular and nervous irritability, hallucinations, rapid heartbeat and repetitive movements. Not only is the fruit of Day Jessamine toxic – the leaves, despite a low alkaloid content, contain cardioactive saponins that resemble ouabain27 (Morton 1982). The Cestrum genus provides an interesting illustration of how investigations of animal poisoning can lead to significant pharmacological insights. In the 1970s reports of Cestrum diurnum toxicity in cattle and horses involved incidents of excessive blood calcium (hypercalcaemia) that resulted in calcinosis (calcification) of soft tissues (tendons, ligaments and vital organs) and serious wasting – as well as reduced fertility. In Argentina, Solanum malacoxylon (now S. glaucophyllum) was implicated in similar incidents.28 Investigations determined that an excessive amount of a hormonally active form of vitamin D, which was present in both species, was responsible for the excessive calcium deposition (Gimeno 2000; Wilson 1997; Boland 1988; Morton 1982; Norrdin 1979; de Vernejoul 1978; Krook 1975). The levels of the 27 Also known as g-strophanthin: a poisonous cardioactive glycoalkaloid from some African Apocynaceae herbs that was formerly used for treating heart problems, notably atrial fibrillation and cardiac failure. Due to its toxicity and problems with bioavailability it was replaced by Digitalis. 28 Reports from various countries have indicated other species have calcinogenic properties: S. torvum (Papua New Guinea), S. esuriale (Australia), S. verbascifolium (South Africa) (Mello 2003).


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Interestingly, Solanaceae with calcinogenic (calcification) potential include the Tomato (Lycopersicon esculentum, plant), Eggplant (Solanum melongena, herb) and Tree Tobacco (Nicotiana glauca) (Krishnaswamy & Raghuramulu 1998). (Image courtesy David Besa, Wikimedia Commons, CC-by-SA 2.0)

active form of vitamin D were determined: Solanum malacoxylon (82,800 IU vit D/kg), Cestrum diurnum (63,200 IU vit D/kg)29 (Mello & Habermehl 1998). This calcinogenic property may have some practical benefits. Vitamin D3 is used for the prevention of disorders such as osteoporosis to increase the intestinal absorption of calcium. The hormonal properties of calcium are essential to calcium and phosphorus metabolism. Vitamin D2 (ergocalciferol) is a plant sterol and is the most common dietary source of this vitamin. However, vitamin D3 (cholecalciferol) can have significantly more activity – up to 2–30 times that of vitamin D2. Hormonally active forms of vitamin D are therefore of significant clinical interest where there are compromised calcium levels, particularly in metabolic disorders affecting bone integrity (Mello 2003). Moreover, these plants have potential for use in poultry farming. Eggshells become increasingly fragile at the end of the annual egg-laying cycle and supplementation to prevent this could be of significant economic benefit. Studies of the use of Cestrum diurnum as a food supplement for poultry showed that eggshell thickness was enhanced and breakages thereby reduced (Chennaiah 2004). Solanum glaucophyllum supplementation in broilers has also shown benefits for phosphate metabolism and bone integrity (Cheng 2004). 29 Lower levels were found in Trisetum flavescens (12,000 IU vit D/kg), and Nierembergia veitchii (16,400 IU vit D/kg) (Mello & Habermehl 1998; Wilczek 1978).

Green Cestrum (Cestrum parqui) is a toxic shrub that has been linked to incidents of cattle poisoning in Australia (McLennan 1984). Strangely enough, there have been reports of Cestrum laevigatum and C. parqui being sold in Brazil as marijuana substitutes – a use more likely to land the participant in hospital than elicit a recreational experience. Green Cestrum contains solasodine and has demonstrated anti-inflammatory and anti-aggregatory effects on blood platelets. Decoctions of the Mexican herb Cestrum dumetorum have been used for the treatment of skin disorders (Shehnaz 1999; Lewis & Elvin-Lewis 1977).

 It is obvious that the remarkable medicinal value of the Solanum genus lies not only in the provision of steroidal substances that inspired a revolution in birth control strategies and the treatment of innumerable inflammatory disorders. Although a couple of Australian species gained international recognition for providing solanine resources for drug development, there is a paucity of knowledge with regard to the other native species. Their role as Aboriginal medicinal

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plants is largely obscure – although their widespread culinary use continues. Certainly, we know much more about the naturalised weedy species. The successful use of these plants as anti-fungal, antiviral (anti-Herpes), immunomodulatory, hepatoprotective, antidiabetic and anticancer agents suggests that there is much to learn – and highlights how little we truly know about the remarkable diversity of native species that inhabit this continent.

Native bees (Tetragonula sp.) feeding on Solanum echinatum, a tropical Australian species of Western Australia (Kimberley region), the Northern Territory and Queensland (west).

Solanum echinatum has been an important food resource for wildlife. Not only do bees seek the flower pollen, the herb is known to be part of the diet for Rock-rats and the Black Wallaroo in Arnhem Land (www.flora.sa.gov.au). Doubtless other native animals utilise it as a part of their diet. The fruit has a very prickly cover (calyx), within which is a typical Solanum berry. Nutritional analysis has shown it is a good source of carbohydrate, fibre and moisture, with various minerals: calcium, magnesium, phosphorus, zinc and fairly high levels of potassium, although no data is available on the vitamin content (NUTTAB database: Nutrient Tables for use in Australia, Indigenous Foods Data File, 2010). This is one of the species that was collected in 1810 by Robert Brown and included in his Prodromus Florae Novae Hollandiae. (Images courtesy Craig Nieminski)

Burdulba Creek, Northern Territory. An evocative image of the Australian bush showcases the unique beauty of this ancient land. (Courtesy Craig Nieminski, flickr)

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INDEX α α-aescin 125 α-bisabolol 67–70 α-cadinol 82 α-calacorene 82 α-cedrene 328 α-chaconine 455 α-copaene 97, 104 α-cubebene 70 α-humulene 101, 142, 462 α-linolenic acid 34, 119 α-muurolene 82 α-phellandrene 177, 316, 462 α-pinene 33, 43, 56, 95, 101, 104, 177, 300, 315, 316 α-solamargine 455 α-solanine 455, 465 α-solasonine 455 α-terpineol 44, 101, 320 α-terpinolene 95, 104, 462 α-terpinyl acetate 95 α-terthienyl 85, 86, 87 α-thujene 104 α-tocopherol 31, 119, 140 α-tomatine 455 α-zingiberene 104 β β-aescin 125, 128 β-bisabolene 44 β-bourbonene 104 β-carotene 31, 32, 33, 117, 119, 142 β-caryophyllene 97, 104, 142, 319, 462 β-chaconine 485 β-cryptoxanthin 33 β-eudesmol 313, 318 β-farnesene 104 β-ionine 82 β-lactamase 321 β-phellandrene 44, 104 β-pinene 33, 95, 104, 315, 316, 462 β-selinene 101 β-sesquiphellandrene 44 β-sitosterol 150, 171, 435, 445, 477, 479, 481 β-soladulcine 455 γ γ-cadinene 82 γ-elemene 88, 315, 318 γ-muurolene 82, 319 γ-terpinene 43, 101, 104, 316 δ δ-cadinene 82 κ κ-strophanthoside 485 ρ ρ-amino salicylic acid 174

ρ-cymene 43, 101, 104, 462 ρ-cymol 142, 149 ρ-methoxyphenylacetone 42 A Abrus precatorius 184 Acacia 149, 391 ancistrocarpum 256 aneura 269, 392, 407, 426 aulacocarpa 133 auriculiformis 324 bivenosa 324 complanta 133 cuthbertsonii 377 hakeoides 373, 392 kempeana 324 leiophylla 308 ligulata 182, 324, 392 nilotica 83 pendula 299 salicina 375, 391 spp. 394 stenophylla 392 Acanthamoeba castellanii 97 polyphaga 97 Acanthocheilonema vitae 282 Acanthospermum australe 97 acetaminophen 54 acetyl salicylic acid 54 acetylcholine 261, 361, 364, 365, 366, 368, 396, 469 acetylcholinesterase 102, 103, 261, 363, 366 acetyleugenol 43 Achillea millefolium 158 Achyranthes arborescens 184 aspera 184 margaretarum 184 acid acetyl salicylic 54 asiatic 142 benzoic 20 betulinic 150 brahmic 143 caffeic 57, 108 carnosic 144 centellic 143 chaulmoogric 164 chicoric 73 chlorogenic 73, 108, 356, 454 dicaffeoyltartaric 73 gallic 104 hydnocarpic 165 isobrahmic 143 kaurenoic 54, 56, 57, 66

linolic 164 madasiatic 142 madecassic 142, 143 nicotinic 415 oleanolic 56, 80, 338 polygalacic 50 rosmarinic 102, 104, 144, 145 taraxinic 76 terminolic 143 thankunic 143 ursolic 144, 398 Ackama muelleri 393 Acmella brasiliensis 54–57 calva 56, 57 grandiflora 52, 61 grandiflora var. brachyglossa 52 grandiflora var. discoidea 52 grandiflora var. grandiflora 52 oleracea 51, 52, 56 paniculata 52 uliginosa 52 Acmena smithii 91 Aconite 10, 47, 212 Aconitum napellus 10, 212 Acorus calamus 151, 152 Actinomadura madurae 200 Actinomyces antibioticus 200 actinomycin 200, 205 Adansonia gregorii 133 adonidin 25 adonilide 26 adonin 26 Adonis 24, 25, 26 Amur 26 amurensis 26 microcarpa 24, 25 Summer 25 vernalis 25, 26 adonitoxin 25 adrenaline 12, 325 adriamycin 201 Adriana glabrata 420 Adrucil 35 Aedes aegypti 87 fluviatilis 64 Aegiceras corniculatum 182, 183 aegicerin 182 Aeromonas hydrophila 148 aescin 124–9 aesculin 73, 124, 125, 130 Aesculus hippocastanum 124–6 indica 126 affinin 57 African Marigold 84, 85

541

Agave 447, 482 amaniensis 447 americana 448 cantala 482 rigida 447 sisalana 447, 448 spp. 451 aglycone 455 Agrimonia pilosa 475 Agrobacterium tumefaciens 55 Agrostis stolonifera 330 Ailanthus altissima 184 glandulosa 184 integrifolia 184 triphysa 184 Ajuga australis 133 Alchemilla speciosa 129 aldrin 237 Aleurites moluccana 156 Allium bakeri 65 sativa 158 sativum 174 Allocasuarina littoralis 133 Allolobophora caliginosa trapezoides 288 allopurinol 130 Aloe vera 121, 481 Alpinia arctiflora 184 arundelliana 184 caerulea 184 galanga 184 hylandii 184 modesta 184 racemigera 184 Alstonia 393 actinophylla 316, 393 constricta 392, 394 scholaris 393 Alternaria alternata 103 solani 335 Amanita muscaria 123, 367 phalloides 368 Amaranthus chlorostachys 82 Amegilla cingulata 308 American Nightshade 451, 464–6, 482–4 aminoglycoside 483 Amitermes laurentis 302 meridionalis 302 Amla 151 Amorphophallus

542


campanulatus 184 galbra 184 paeoniifolius 184 amphotericin 483 Amulla 294 Amur Adonis 26 Amyema quandong 133 anabasine 396, 398, 406, 407, 412, 415, 416 anagyrine 415 Ancylostoma caninum 276 duodenale 274, 276 Andrographis paniculata 64 androstenedione 434 anethole 42, 44 Anethum sowa 39 Angel’s Trumpet 354, 350, 395 Angelica sinensis 69, 475 Anise oil 20, 42 Aniseed 42 anisodamine 359, 360 anisodine 359, 360 ankaflavin 441, 443, 444 Annona cherimolia 54 glabra 54 senegalensis 54 squamosa x A. cherimolia 55 anonaine 177 Anopheles stephensi 101, 116, 149 subpictus 87, 149 anthecotulide 68 anthelminthicin 170 Anthemis arvensis 66, 67 cotula 68 nobilis 66, 68 Antheum graveolens 43 Anthocercis aromaticus 398 fasciculata 398 frondosa 398 genistoides 398 ilicifolia 398 littorea 398 viscosa 398, 399 anthocyanidin 19, 130 Anthotroche myoporoides 398 pannosa 398 walcottii 398, 399 antimony 209, 210 anymol 327 apigenin 66, 67, 69, 120, 171, 172, 179, 429 apigenin 7-glycoside 70 Apis 47 Apis mellifera 307 apoatropine 355, 358, 396, 398 Apocynum 212 Apodemus sylvaticus 281 aporphine 177 aposcopolamine 396, 398 Apple Bitter 454 Custard 55 Devil’s 477 Kangaroo 454, 456 Mountain Kangaroo 454 Winter 294 Wolf 478

Apple of Sodom 475 Applebush 96, 182 Ara chloropterus 223 Arabidopsis thaliana 469 Araucaria bidwillii 133 Areca catechu 372 Armoracia rusticana 378 armyworm, Asian 164 Arnebia euchroma 475 Arnica 47, 59, 79 Arnica montana 58 aromadendrene 300, 318, 327 arsenic 230, 231 Artemisia annua 97, 98 capillaris 129 montana 129 scoparia 129 artemisinin 97 asbestos 226, 236, 237, 476 Ascaris lumbricoides 165, 275, 279, 280 suum 280 trichuris 275 ascorbic acid 32, 33, 119, 445 asiatic acid 140, 142–4, 148, 149 6-β-hydroxy-asiatic acid 143 asiaticoside 140, 142–4, 146, 148, 149, 155 asimilobine 177 Aspalathus linearis 172 Asparagus racemosus 151 Aspergillus 55, 56, 69, 194, 199, 482 flavus 55, 56, 217, 335, 462 niger 50, 55, 56, 121, 133, 135, 148, 335 parasiticus 55 aspirin 54, 57, 130, 149, 192 Asteromyrtus shepherdii 133 symphyocarpa 133 Astragalus membranaceus 64 Astrotricha longifolia 133 Atalaya hemiglauca 306 variifolia 307 Atemoya 54, 55 Athanasia crithmifolia 328 Atropa belladonna 341, 342, 353, 355, 357, 359, 384, 394, 463 atropine 220, 227, 341, 344–6, 349, 353–60, 362, 364, 366, 368, 384–90, 394–6, 401, 415, 463, 472, 488 Attar of Roses 30, 31 aureomycin 198 Australian Buckthorn 123 Australian Corkwood 387 Australian Paralysis Tick 412 Australian Sneezewort 50 Australian Tobacco 404 Azadirachta indica 39, 164, 184 Aztec Marigold 83, 84, 87 azulene 67 B Bacillus cereus 36, 54, 132, 148, 335 dysenteriae 109 megaterium 148 subtilis 29, 55, 56, 80, 98, 103, 109, 121, 133, 148, 244, 334, 459 typhi 109 Backhousia citriodora 131, 133 Bacopa

floribunda 150 monnieri 137, 150, 152, 158, 428 procumbens 150 bacosine 150 Bacteroides vulgatus 36 Bai-ji 174 Baileyoxylon lanceolatum 166, 167 Balanops australiana 133 Bandicoot, Southern Brown 285 Banksia collina 133 Baptisia alba 415 Barbat Skullcap 474, 475 Barmah Forest virus 203 Basil 98, 179 Bastard Sandalwood oil 131 Bat Plant 446 Baylisascaris procyonis 275 Beach Sunflower 53, 56, 59, 60, 61, 156 Bean Calabar 362 Mescal 416 Ordeal 361 Soya 480 beauvericin 435 BEC 476 Bee Blue Banded 308 Cuckoo 308 Belladonna 18, 349, 383–8 belladonnine 355 Belleric Myrobalans 151 Bellis perennis 48, 49, 50 Benamanrka-gunara 266 bentonite 217, 221, 226–8, 234, 238, 240, 253, 254, 256, 271, 273, 275 benzocaine 371 benzoic acid 20 benzoin 46, 437 benztropine 359 berberine 97, 112, 171 Berberis aristata 39 Bergamot oil 105 Bergsmia javanica 167 Berrigan 316, 320 Berry, Turkey 458 Beta vulgaris 344 betalain 122 betaxanthin 122 Betel Nut 116, 372, 373, 392 betulinic acid 35, 143, 150, 171 Beyeria lechenaultii 133 bicyclogermacrene 142 Bidens bipinnata 184 pilosa 184 subalternans 184 tripartita 184 biflorin 316, 318, 319, 328 Bilberry 385, 386 Bilharzia 280, 282 Biomphalaria peregrina 54, 57 bisabolene 315, 327 bisabolol 67, 69, 70, 80 bisphenol A 123 Bitter Apple 454 Bitter Jessie 440 Bitter Yam 438, 439 Bitterbark 394 Bittersweet 189, 455, 462–4, 470, 471, 472 Black Garlic 175 Black Hellebore 486, 487

Black Lily 446 Black Nightshade 451, 455, 462–6, 468–74, 483 Black Orchid 419 Black Pepper 417 Blackbean 2, 131, 418 Blainvillea dubia 52 gayana 52 bleomycin 201 Bletilla striata 174 Blue Coleus 103 Blue Gum 149, 190 Blue Lobelia 423 Blueberry Tree 293 Boerhaavia diffusa 39 Bombyx mori 284 Bontia daphnoides 297 Boobialla Common 293 Creeping 293 Pointed 380 Southern 293 Western 294 Boophilus decoloratus 454 Borage, Indian 100 Bordetella bronchiseptica 334 pertussis 281 borneol 43, 44, 70, 95, 316, 320 bornyl acetate 70, 320 Boronia 32 Boronia megastigma 32 spp. 133 Boswellia carterii 75 Botrytis cinerea 54,135 Bottlebrush 182 Bougainvillea spectabilis 129 Brachychiton acerifolius 133 Brahmi 137, 150, 151, 158, 428 Brahmia indica 150 Brahmic acid 143 brahminoside 143 brahmoside 143 Brazilian Cress 53 Brazilian Nightshade 451 Brazilian Pennywort 139 Brazilian Potato Tree 451 Brown Plum 370, 371 Brucea javanica 172, 184 bruceantin 172 bruceine 172 bruceoside 184 Brugia malayi 280 Brugmansia arborea 395 knightii 395 sanguinea 354, 355, 356 suaveolens 395 x candida 395 Buckinghamia celsissima 133 Buddleia cordata 179 Buddleja davidii 179 globosa 326 Bufo marinus 341 bufotenin 341 Bulbine frutescens 140, 141 Bulrush 220 Bunya Nut 133 Burn Jelly Plant 141 Bursaria calciocola 124

INDEX incana 123 longisepala 124 occidentalis 123, 124 reevesii 124 spinosa 123, 125 tenuifolia. 123 Buruli ulcer 175, 202, 203, 286 Buscopan 401 Bush Cattle 420 Coca 370 Crimson Fuchsia 315 Desert Fuchsia 315 Drummond’s Poverty 324 Ellangowan Poison 294, 311 Flannel 452 Harlequin Fuchsia 314, 321 Kerosene 318 Narrow-leaf Fuchsia 313 Pituri 380 Purple Fuchsia 315 Red Poverty 314 Rock Fuchsia 315 Smelly 88 Spotted Fuchsia 317 Spotted Poverty 323 Tar 297 Turkey 315 Turpentine 314, 318, 321 Warty Fuchsia 311 C Cabbage Rose 38 Cacalia ainsliaeflora 329 decomposita 329 delphinifolia 329 pilgeriana 329 cacalohastin 330 cacalol 325, 330 cacalone 329 Cachexia Africana 273 cactinomycin 200 cadinane 327 cadinene 70, 82 cadmium 233 Caesalpinia bonduc 185 crista 185 digyna 185 erythrocarpa 185 hymenocarpa 185 major 185 nitens 185 pulcherrima 185 robusta 185 sappan 185 subtropica 185 traceyi 185 caffeic acid 57, 70, 104, 108, 119, 144 Calabar Bean 362 calamenene 327 Calamphoreus inflatus 297 calcalone 330 Caldcluvia paniculosa 393, 394 Calendula alata 82 arvensis 67, 81 officinalis 77–9, 81, 141 Calendula oil 80 calenduloside B 81 Callistemon citrinus 133, 182

salignus 133 Caloncoba echinata 163 Calotropis gigantea 170 Camel Poison 378 Camellia sinensis 58 campesterol 435, 445, 479, 480 camphene 44 camphor 20, 43, 178, 185 camphora 47 camphorene 327 Campylobacter jejuni 81 Candida albicans 35, 55, 56, 81, 103, 113, 121, 133, 148, 172, 205, 298, 330, 334, 335, 436, 459, 462, 482 dubliniensis 81 glabrata 81 guilliermondii 81 krusei 81, 139 maltosa 334 parapsilosus 81 tropicalis 56, 81 Cane Toad 341 Canine hookworm 276 Canine roundworm 276 Canine whipworm 276 Canna indica 83 cannabichromene 192 cannabidiol 191, 192 cannabidiolic acid 191 cannabigerol 191, 192 cannabigerolic acid 191 cannabinol 192 Cannabis sativa 185, 191, 347 Canscora decussata 185 diffusa 185 cantalasaponin-3 482 Canthium oleifolium 91 Cape York Lily 159 Capparis spinosa 158 Capraria biflora 319, 320 lanceolata 319 Capsella bursa-pastoris 185 capsicastrine 477 capsimine 477 Caraway 43 Caraway oil 43 carbon-tetrachloride 57 Cardamomum 39, 43 Cardinal Flower 425, 429 cardiogenin 37 Carduus marianus 158 Carica papaya 185 Carissa lanceolata 133 carnosic acid 144 carnosol 144 carotene 40, 142 carpesterol 459, 477, 482 Carpotroche brasiliensis 163, 165, 173 Carum carvi 43 carvacrol 101, 104 carvacrol acetate 104 carveol 43 carvone 43, 45 caryophyllene 43, 88, 101, 104, 142, 149, 462 caryophyllene oxide 104, 462 Casearia grayi 133 multinervosa 133

sp. (Mission Beach) 133 Cassia occidentalis 53, 158 Cassia bark 43 Cassowary 168 Castanospermum australe 2, 131, 133, 418 casuarictin 36 Casuarina cristata 185 cunninghamiana 185 equisetifolia 185 glauca 185 obesa 185 pauper 185 catalpol 317 catechin 128, 142, 445 Catha edulis 373 Catharanthus roseus 10, 185 Cattle Bush 420 Cauliflower, Pink 95 Caulinia nigricans 202 Cedrus deodara 39 Celery seed oil 105 Centella asiatica 137, 138, 140, 141, 144, 147–50, 152, 155, 156, 169, 428 cordifolia 144 centellasaponins 143 centellic acid 143 centelloside 143 Centipeda borealis 105 crateriformis 106 cunninghamii 50, 105, 108, 133 minima 105, 108, 109 minima subsp. macrocephala 105 minima subsp. minima 105 nidiformis 106 orbicularis 105 pleiocephala 106 racemosa 106 thespidioides 105, 106 Ceratanthus longicornis 133 cerubidin 201 Cestrum diurnum 488, 489 dumetorum 489 elegans 487, 488 fasciculatum 487 Green 488, 489 laevigatum 489 nocturnum 488 Orange 488 parqui 488, 489 Red 487 cevadine 485 chaconine 455, 460, 481 chacotriose 460 Chagas disease 57 Chamaemelum nobile 66, 67 chamazulene 67, 69, 70 Chamelaucium uncinatum 94, 95 Chamomile Corn 66, 67, 180 German 66, 67, 81 Lawn 68 Roman 66–68, 81 True 66 Yellow 67 Chamomilla recutita 66 chard 86, 344 Chatham Island Pratia 430 Chaulmoogra 161, 164

543 chaulmoogra oil 161–4, 166, 169, 170, 171, 173 chaulmoogric acid 164, 165,170 chavicol methyl ether 42 Chebulic Myrobalans 151 Chenopodium album 82 Cherimolia 54 Cherokee Rose 33, 38 Cherry, Jerusalem 478 Chestnut Rose 29, 33 Chicoric acid 73 Chicory 48, 73, 129 China Rose 29 Chinese Black Nightshade 466 Dandelion 74, 75, 76 Goldthread 171 Hawthorn 29 Holly 475 Lobelia 428, 430 Sage 146 Tea Rose 38 Wedelia 63, 65 chitinase E 436 Chlamydia pneumoniae 172, 178 trachomatis 208, 278 Chlamydophila pneumoniae 178 chloramphenicol 197, 445, 460 Chlorocebus pygerythrus 263 chlorogenic acid 73, 108, 356, 454 chloromycetin 197, 198 chloroquine 201, 220, 460 chlortetracycline 198 choline 70 Chondrodendron tomentosum 362 Chromobacterium violaceum 29 Chrysanthemum, Florist’s 180 Chrysanthemum leucanthemum 48 morifolium 180 segetum 180 sinense 180 chrysoeriol 171 chrysoplenetin 97, 98 chrysosplenol 96, 97, 98 cichoriin 73 Cichorium intybus 73, 129, 158 Cinchona 377, 388, 394 cineole 43–5, 95, 190, 314, 327 1,8-cineole 95, 327 cinnabarite 213 cinnamic acid 70 cinnamic aldehyde 43 Cinnamomum baileyanum 185 camphora 43, 178, 185 iners 185 laubatii 185 oliveri 185 propinquum 185 virens 185 zeylanicum 43, 178, 185 Cinnamon 29, 43, 67, 178, 211 ciprofloxacin 75 cis-chrysanthenol 108 cis-chrysanthenyl acetate 108 cisplatin 120, 128 Cissampelos pareira 185 Cistuscreticus 19 cis-β-farnesene 70 citral 44, 87 citrinin 443

544


citronellal 44, 87, 95 citronellol 29–31, 33 Citrullus colocynthis 185 lanatus 185 vulgaris 185 Citrus aurantium 42, 44 aurantium subsp. bergamia 44 limon 44 reticulata 75 Cladanthus multicaulis 67 Clausena brevistyla 185 excavata 185 smyrelliana 185 sp. Tipperary 185 Claviceps purpurea 341 Clavija procera 182, 183 Clematis aristata 110 brachiata 111, 113 chinensis 114 cirrhosa 111, 113 dioica 113 Erect 112 flammula 114 glycinoides 110 hirsuta 111, 113 ligusticifolia 112, 113 microphylla 110 montana 113 oweniae 111, 113 papuasica 111, 113 pickeringii 133 recta 111, 113 sinensis 113 Small 110 virgiana 112 vitalba 110, 111 Western 113 Cleome droserifolia 115, 117 gynandra 115, 116, 117 hassleriana 116 rutidosperma 118 viscosa 114–6, 118 cleomin 115 Clerodendron traceyi 134 Clerodendrum floribundum 133 clinoptilolite 240, 242 clofazimine 160 Clonorchis spp. 280 Clostridium difficile 207 perfringens 199, 321 tetani 199 Clove 36, 43, 67, 319 Clove oil 43 cocaine 46, 341, 370 Coccidioides immitis 199 cochlearin 378 Cocky Apple 180, 181 codeine 22, 23, 38, 121, 341 Codonocarpus attenuatus 376, 377 australis 378 cotinifolius 376–8 pyramidalis 376 Coelospermum paniculata var. syncarpum 187 colchicine 130 coleon A 99, 101

Coleus 99 amboinicus 101 aromaticus 101 barbatus 101 coerulescens 101 kilimandschari 101 vettiveroides 102 Colocasia esculenta 439, 441 colupulone 333 Comfrey 48, 50, 51, 120 Commiphora myrrha 75 Common Broom 416, 417 Brushtail Possum 176 Daisy 48 Thornapple 350 coniine 415 Conospermum brachyphyllum 134 incurvum 134 convallamarin 27 Convallaria majalis 26, 27 convallarin 27 convallatoxin 26, 27 Convolvulus angustissimus 185 arvensis 185 clementii 185 crispifolius 185 erubescens 185 eyreanus 185 graminetinus 185 microcephalus 185 pluricaulis 152 recurvatus 185 remotus 185 tedmoorei 185 wimmerensis 185 Conyza aegyptiaca 186 canadensis 469 sumatrensis 186 Copi 267 Coptis chinensis 171 Coptotermes acinaciformis 301 formosanus 300 coramsine 476 Cordyceps sinensis 474 Cordyline terminalis 294 Coriander 43 coriandrol 43 Coriandrum sativum 43 Cork Oak 393 Cork-tree 393 Corkwood 379 Duboisia 381–3, 393, 395–8, 417 Australian 387 Laurel 394 Leichhardt 380, 393, 397 Corn Chamomile 66, 67 Corynebacterium diphtheriae 55, 56, 75 Corynocarpus laevigatus 295 Costus speciosus 449 Cotula tinctoria 67 coumarin 67, 70, 80, 84, 129, 185, 429 Crataegus cuneata 29 oxyacantha 28 pinnatifida var. major 29 Creeping Bentgrass 330

Crenidium spinescens 398 Cress Brazilian 53 Daisy 48, 52, 61 crocidolite 236 Crotalaria incana 92 Cryptocarya corrugata 134 Cryptococcus neoformans 96, 482 Cucumis melo 197 Cucurbita maxima 186 pepo 186 Culex quinquefasciatus 58 Curaderm 476, 477 curare 362–4, 382 Curcuma amada 159 australasica 159, 186 domestica 158, 186 longa 64, 158, 159, 186, 475 curcumene 44 curcumin 159 Curvularia lunata 103 cuscohygrine 359 Custard Apple 55 cyanide 243, 244 cyanidin 119 Cylas formicarius elegantulus 319 cymarin 25, 26 Cymbidium canaliculatum 419 Cymbopogon ambiguus 134, 315 Cyphanthera anthocercidea 398 odgersii 398 tasmanica 398, 399 cytisine 415, 416, 417, 418 Cytisus scoparius 416, 417 D dactinomycin 200 daidzein 443 Daintree ulcer 203 Daisy 10, 46, 55 Alpine 58 Common 48 Singapore 60, 62, 138 Sunflower 59, 61 Daisy Cress 48, 52, 61 Damask Rose 29, 30, 35 Dandelion 46, 48, 64, 70–7, 82, 158, 189 Chinese 74–6 Japanese 75 Russian 70, 77 dapsone 160, 170 dasyscyphin-C 65 Datura 341, 350, 356 Purple 346 White 346 Datura alba 347 arborea 395 fastuosa 354, 356 ferox 346, 350, 351, 356 inoxia 345, 346, 351, 356 leichhardtii 349, 350 metel 345–7, 350, 351, 356 metel var. fastuosa 346, 347 stramonium 346, 349–54, 357, 384 stramonium var. tatula 354 wrightii 350 daturamine 359 daunomycin 201

daunorubicin 201 Day Jessamine 488 DDS 160 DDT 58 Deadly Nightshade 342, 353, 355, 357, 383, 463 dehydrongaione 313, 314, 328 dehydrotomatine 455 dehydroxyserrulatic acid 328 delphinidin 477 deltonin 445 deltonine 435, 436 deltoside 436 dendrolasin 327, 328 Dendrolasius fuliginosus 328 deptropine 359 Desert Poplar 376, 377 Desert Sneezeweed 105 Desert Thornapple 349 desmethylwedelolactone 64 Devil’s Apple 477 Devil’s Fig 458, 459, 460, 483 D-galactosamine 57 D-germacrene 104 D-glucoside 459 DHEA 434 Di Long 287, 288 diamino-diphenyl-sulfone 160 Diamondback moth 116, 300 Dianella callicarpa 134 longifolia var. grandis 134 revoluta var. revoluta 134 dicaffeoyltartaric acid 73 2,4-dichlorophenol 123 Dictamnus dasycarpus 446 Didymotheca cupressiformis 378 dieldrin 237 Digitalis 25–8, 370, 488 purpurea 10, 24, 449 digoxin 225, 227, 449 dihydrocarveol 43 dihydrocarvone 43 Dill 43 dillapiole 43 dimaturin 329 dimerumic acid 441 dimethylnitrosamine 454 Diocirea microphylla 297 ternata 297 diosbulbin 437, 445 dioscin 435, 438, 440, 445–77 dioscorans 438 Dioscorea alata 434, 436, 441 alata var. purpurea 441 batatas 438–41, 444 birmanica 446 bulbifera 436–8, 442, 444, 445 bulbifera var. sativa 437 cayenensis 436, 439 cirrhosa 441 collettii 435, 445 collettii var. hypoglauca 445 composita 433, 435 deltoidea 433, 435 deltoidea var. orbiculata 445 dumetorum 438, 439 elephantipes 433 esculenta 441, 446 floribunda 433, 435 futschauensis 445

INDEX hispida 437, 438, 446 hypoglauca 437 macrostachya 432, 433 membranacea 446 mexicana 435 nipponica 440, 446 opposita 436–8, 441, 442 panthaica 440 polygonoides 439, 440 prazeri 433, 435 pseudojaponica 434, 442 septemloba 437, 440 spongiosa 440 spp. 439, 441–2 sylvatica 435 tokoro 435, 437, 438 transversa 444 villosa 439 zingiberensis 435, 441 dioscorealide 446 dioscoretine 438, 439 dioscorin 441 diosgenin 432–5, 437–42, 445–50, 452, 454, 461, 479 dipentene 44 dipyrone 54 Dirofilaria immitis 149 dl-hyoscyamine 341 Dodonaea angustissima 332 boroniifolia 331 falcata 331 filifolia 331 microzyga 332 physocarpa 337 spp. 334–7 triquetra 332 uncinata 338 viscosa 178, 269, 330–3, 339 viscosa subsp. angustifolia 333 viscosa subsp. angustissima 332 viscosa subsp. burmanniana 331 viscosa var. angustifolia 178, 337 Dog Rose 32 dopamine 122, 325, 428 Doryphora sassafras 134 Doughwood 393 Downy Thornapple 350 doxorubicin 148, 200, 201, 478 Drimia maritima 27 Drymaria cordata 186 Dryopteris crassirhizoma 319 Drypetes lasiogyna 134 DTO 23 d-tubocurarine 362 Duboisia arenitensis 380, 398 campbellii 380 hopwoodii 106, 372, 375, 376, 379–83, 389, 391, 392, 398, 402–4 leichhardtii 379, 380, 389, 393, 397, 398 myoporoides 358, 379–81, 383, 387, 389, 393–8, 401 duboisine 341, 386–90, 392 Duchesnea indica 474, 475 Dudo 163 Dudoa 163, 165 Dugong dugon 285 duingira 266 dulcamarine 471

E earthworm 286, 287 Giant Gippsland 289 Common 288, 289 ecdysteroids 435 Echinacea angustifolia 158 purpurea 158, 159 eclalbasaponin I 65 Eclipta alatocarpa 186 alba 56, 63, 64, 65, 186 platyglossa 186 prostrata 63, 64, 186 EDDS 469 EDTA 82, 469 Eggplant 451, 452, 455, 473, 476, 477, 485, 489 Ethiopian 473 Eglantine 29 Eisenia fetida 289 Elecampane 180 elemene 142 elemicin 44 elemol 313, 314, 328 Elephantopus mollis 186 scaber 186 spicatus 186 Elettaria cardamomum 39 cardamomum var. misicula 43 ellagic acid 128 Ellangowan Poison Bush 294, 311 Embelia schimperi 182 Emblic officinalis 151 Emu-bush 315, 323 Coccid 292 Silver 296 Weeping 316 Encosternum delegorguei 337 Endiandra sieberi 393, 394 Entamoeba histolytica 57, 109, 149, 155 Enterobacter aerogenes 471 Enterococcus faecalis 321, 337 Ephedra distachya 12 equisetina 12 intermedia 12 major subsp. procera 12 sinica 12 ephedrine 12, 341, 363 epi-ɑ-muurol 82 epicacalone 329, 330 Epidermophyton 54 epingaione 295, 328 epipinoresinol 312, 317, 325 epoxycembranediol 328 epsomite 240 eremolactone 315, 328 Eremophila 16, 131, 134, 297, 315, 318 abietina 323 alternifolia 183, 313, 325 beckeri 297 bignoniiflora 292, 313, 325 cuneifolia 313 dalyana 314 debilis 292 decipiens 329 deserti 294, 311 drummondii 324

duttonii 314, 321 elderi 314 fraseri 314, 321 freelingii 315, 323 gibbifolia 292 gilesii 315 glabra 297 hygrophana 293 latrobei 292, 311, 316, 318 latrobei subsp. glabra 316 linearis 321 longifolia 183, 292, 312, 316, 320, 325 maculata 292, 296, 309–12, 317, 324 maculata ‘Aurea’ 310 mitchellii 131, 292, 294, 297–9, 317 neglecta 318, 324 nivea 291 oldfieldii 292 paisleyi 318 racemosa 312 saligna 380 scoparia 296 Showy 312 Silky 291 spp. 327 sturtii 318 subteretifolia 291 virens 324 eremophiladienone 300 eremophilane 300, 325, 327, 329, 330 eremophilone 298, 299, 300, 317, 327 ergosterol 479 ergotamine 370 Erwinia carotovora 29 Erythrina indica 186 variegata var. orientalis 186 vespertilio 134, 186, 315 erythromycin 199, 483 Erythroxylum australe 370 coca 370 coca var. ipadu 370 coca var. truxillense 370 ecarinatum 370, 371 ellipticum 370 monogynum 371 ESBL 202 Escherichia coli 29, 36, 54–6, 80, 98, 121, 126, 132, 148, 150, 179, 181, 199, 202, 203, 205, 298, 305, 321, 337, 435, 471 coli IAM1264 244 esculetin 84, 126–30 esculoside 128 E-sesquilavandulyl 97 Essence de Bigarde 44 Essence de Portugal 44 estradiol 434 estrone 434 ethambutol 176 Ethiopian Eggplant 473 ethyl cyclohexane 177 ethyl-chaulmoograte 170 ethylene diamine tetra acetic acid 82, 469 etioline 477

545 Eucalyptus baileyana 136 botryoides 190 camaldulensis 190, 392, 422 camaldulensis subsp. obtusa 190 citriodora 190 coolabah subsp. arida 392 deglupta 190 globulus 36, 149, 190 grandis 190 maculata 190 major 136 nitens 36 pellita 301 populifolia 299 tectifica 268 tereticornis 190 Eucalyptus oil 44, 46, 89, 90 Eucommia ulmoides 325 eudesmane 327 eudesmol 327 Eugenia 91, 189 brasiliensis 186 reinwardtiana 186 eugeniin 36 eugenol 43, 44, 104 Euphorbia australis 132, 134 drummondii 132, 134 hirta 132 obovalifolia 454 peplus 131, 132, 186 Evodia, Pink-flowered 393 Evolvulus alsinoides 151 Excoecaria agallocha 131, 134 F Fagopyrum cymosum 475 faradiol 81 farnesene 44, 70, 104, 142, 149 farnesol 70, 142 Fasciola hepatica 483 Fasciolopsis spp. 280 fenchol 320 fenchone 44, 313, 327 Fennel 44, 313 Fenugreek 448, 450 Ferula communis 178 Fever-bark tree 394 Ficus brachypoda 454 racemosa 134 Field Poppy 19, 20 Field Rose 32 Fierce Thornapple 350 Fig, Devil’s 459, 460 Flammula Jovis 111 Flannel Bush 452 flatworm 279, 280 flavone 70, 314, 485 fluorouracil 35, 70, 128 fluke 280 intestinal 280 liver 280 lung 280 Schistosoma 109, 274, 280, 282, 283, 453, 483 sheep 149 Fly Agaric 123, 367 Foambark Tree 332 Foeniculum vulgare 44 Foetid Hellebore 486 Forest Red Gum 190 forskolin 102, 103

546


Foxglove 10, 19, 24, 28, 449 Frankincense 75 fraxinol 429 Fraxinus bungeana 129 excelsior 129 rhynchophylla 129 freelingyne 315, 327 French Marigold 82, 83, 84 Frogmouth, Tawny 285 Fruit-salad Plant 96 frusemide 53 Fuchsia Native 309, 310, 315, 316, 317, 325 Rock 315, 323 fucosterol 479 furans 316, 327 furfural 70, 328 Fusarium 235, 482 moniliformis 55 oxysporum 55, 56, 103 G Gag-root 429 Galangal 184 Galanthus woronowii 364 gallic acid 29, 35,104, 306 Gan Cao 75 garlic 81, 107, 158, 174, 175, 231, 443 gazaniaxanthin 33 geebung 94 Gelsemium elegans 147 gemcitabine 128 geniposidic acid 313, 325, 327 genistein 443 gentamicin 121, 179 Gentiana lutea 487 gentisic acid 306 geophagy 246, 261, 264, 265, 270, 273–5 Geraldton Wax 94, 95 geraniol 29, 30, 31, 70, 95 geranyl acetate 44, 327 germacrene 97, 104, 142 germacrene D 97, 104 German Chamomile 66, 67, 81 German Chamomile oil 67 Geum 36 japonicum 36, 37 talbotianum 37 urbanum 37 Giardia intestinalis 109 gibberellic acid 397 gidyea 373, 374 Ginger 44, 46, 443, 449 6-gingerol 443 gitogenin 447 Glebionis segetum 180 globulol 300 Glomus claroideum 469 intraradices 469 Glossocarya calcicola 134 glucocapparin 115, 116 glucocleomin 116 Glycine max 448, 480 glycitein 443 Glycocystis beckeri 297 Glycyrrhiza uralensis 75, 346 Godi 163 Golden Marguerite 67 Golden Seal 171 Goldenrod Atlantic 180

Canada 180 Gonococcus vaginalis 39 Goodenia bellidifolia 422 glauca 422 Hairy 422 Hop 422 lunata 392, 422 ovata 421, 422 scaevolina 422 Gorilla beringei beringei 262 gorlic acid 165 Gotu Kola 81, 137, 138, 140–4, 146–9, 151, 155, 158, 428 gout 129, 130, 442 gracillin 435, 445 Grammosolen dixonii 398 Granadilla 421 Great Blue Lobelia 426 Green Cestrum 488, 489 Green Hellebore 486 Green Poisonberry 488 Green-berry Nightshade 465 Grevillea juncifolia 134 pteridifolia 134, 201 robusta 134 stenobotrya 392 striata 134, 392 g-strophanthin 488 Guaiacum officinale 178 guaiazulene 69, 70 Guayule 77 Guduchi 151 Gum Blue 190 Forest Red 190 River Red 190 Gynandropsis gynandra 117 gynocardase 168 Gynocardia odorata 164 gynocardin 165, 167, 168 gypsum 229 Gyrocarpus americanus 382 jacquini 382 Gyrostemon australasicus 378 ramulosus 378 tepperi 378 H Haemodorum simplex 134 Hairy Goodenia 422 Hairy Thornapple 350 halloysite 227 Hansen’s disease 157 harman 412 Hawthorn 28, 29, 130 head lice 57, 412 Headache Vine 110 Hechtia texensis 448 hecogenin 447 Heicoverpa armigera 337 helenalin 59 Helichrysum umbraculigerum 191 Helicobacter pylori 55, 69, 151, 172, 474 Heligmosomoides polygyrus 80, 281 Heliopsis longipes 57 heliotropin 43 Hellebore 486, 487 Black 486, 487 Foetid 486

Green 486 White 486, 487 helleborein 486 helleborin 486 Helleborus foetidus 486 niger 486, 487 hellebrin 486 helminths 14, 275, 278, 279, 290 Helopeltis theivora 58 Hemlock 146 Henbane 346, 358, 384, 394, 463 Black 341, 342, 348 White 348 heneicosane 30 Henna 39, 69 herniarin 67, 80 heroin 22 Herpes genitalis 69 simplex 36, 76, 81, 97, 100, 145, 191, 484, 485 Herpestris monniera 150 Heterodera zeae 87 Heterometrus indicus 65 Hevea brasiliensis 77 hexatriacontane 30 Hibiscus rosa-sinensis 83 tiliaceus 186 trionum 186 vitifolius 186 Hippobroma longiflora 427 Holly, Chinese 475 Homalanthus nutans 131 honey ants 268 hookworm 14, 266, 271, 274–6, 280 Hop Goodenia 422 Horsechestnut 124–8, 137 Horseradish 378 Horseweed 469 Hop-bush Brilliant 332 Common 332 Large-leaf 332 Slender 332 Thread-leaf 331 Huang Lian 171 Humulus lupulus 178, 320, 332 huntite 248, 249 hydnocarpic acid 165 hydnocarpin 170, 171, 172 Hydnocarpus alcalae 163, 165 alpina 164 annamensis 170 anthelmintica 163–5, 170, 171 castanea 163 ilifolia 164 kunstlerii 163 kursii 163 kurzii 164, 165 laurifolia 163, 165 macrocarpa 163 octandra 164 odorata 164 pentandra 161, 163, 170 venenata 163, 164 wightiana 163–5, 170, 171 Hydnocarpus oil 169, 170 hydnowightin 170, 171 Hydrastis canadensis 171 Hydrocotyle

asiatica 137 bonariensis 138, 139 cordifolia 137 leucocephala 139 sibthorpioides 139 hydrocyanic acid 168 hydrocyanide 169, 311 hydrotalcite 238, 240 hydroxycalamenene 327 hygrine 398 Hymenolepis diminuta 281 nana 57 hyoscine 341, 349, 351, 356, 358, 370, 389, 394–8, 400, 402 hyoscyamine 18, 341, 344, 346, 349, 352, 355–9, 366, 384, 387, 389, 390, 394–400, 463 Hyoscyamus albus 348 niger 341, 342, 348, 353, 358, 384, 463 Hypericum 81, 186 gramineum 186 japonicum 186 perfoliatum 81, 428 pusillum 186 hyperoside 28, 338 hypoxanthine 130 I ibotenic acid 368 Ilecis 475 Ilex cornuta 475 Ilicis cornutae 475 Illicium verum 42 illite 202, 203, 221, 263 Ilpara 392 Indian Borage 100 Indian Horsechestnut 126 Indian Lobelia 424 Indian Snakeroot 10 indioside D 461 indole-3-carboxylaldehyde 66 indomethacin 54, 57, 74, 81, 481 Intal 151 Inula helenium 180 inulin 74, 77 Ipomoea batatas 327 digitata 151 purga 178 isobrahmic acid 143 isoelemicin 44 isoeugenol 44 isohydnocarpin 171 isolobelanine 428 isolobinine 425 isomenthone 45, 316, 320 isomyodesmone 328 isoniazid 174, 176 Isoodon obesulus 285 isoquercitrin 73 isosolafloridine 454 isothakuniside 143 Isothankunic acid 143 Isotoma anethifolia 425 axillaris 425 hypocrateriformis 427 longiflora 427 petraea 134, 424, 426 Isotome, Rock 424, 426, 427 Ixodes holocyclus 412

INDEX J Jacksonia scoparia 134 Jagera pseudorhus 332 Jalap 178 Jambul 178 Japanese Dandelion 75 Japanese Peppermint oil 45 Japanese Scopolia 360 Japanese Yam 435, 437 Jatamansi 151 Javan Ash 166 Jerusalem Cherry 478 Jessamine 146, 487, 488 American Yellow 147 Day 488 jetrorrhizine 112 Jimson Weed 349, 352 Juniper, Native 293 Juniperus communis 178 excelsa 178 procera 178 sabina 105 K kaempferol 40, 119, 120, 142, 334, 356, 471 kakadumycin 201 Kalaw 163 Kallstroemia pubescens 448 Kangaroo, Grey 285 Kangaroo Apple 452, 454, 456 kaolin 214–6, 220, 221, 226, 227, 236, 247, 255, 263, 266, 272, 273 kaopectate 215, 216 karahanaenone 316, 320 Karaka 295 kaurenoic acid 54, 55, 56, 57, 61, 62, 66 Kemiri nut 156 Kennedia nigricans 134, 201, 202 Kerosene Wood 370 Khaki Bush 86 Klebsiella pneumoniae 81, 103, 132, 330 kohl 208, 209, 232 Kohoho 457 Kohuhu 178 Kombe 26 L Laburnum anagyroides 416 Lactobacillus plantarum 37 Lactuca virosa 470 lactucarium 469, 470 Ladanum 19 Lampito mauritii 288 Large-leaf Pennywort 138 Laudanum 19, 20, 23 Laurelia novae-zelandiae 176, 177 sempervirens 177 Laureliopsis philippiana 177 laurionite 209, 210 Lavender 29, 81, 145 Lawn Marsh Pennywort 139 Lawsonia inermis 39 lead poisoning 231 ledene 82 leech 106, 107 Leichhardt Corkwood 380, 393, 397 Leishmania 54, 101, 274, 483 amazonensis 101, 120, 139 braziliensis 57 donovani 172

Lemon 40, 44, 131 Lemon Balm 145, 178 Lepidosperma viscidum 134, 324 Leptospermum petersonii 134 Leptospira 277 Leucojum aestivum 364 levartenol 121 lice 322, 435 head 57, 412 lichen 39, 258 lidocaine 371 lignocaine 371 Ligularia macrophylla 300 Ligustrum lucidum 64 Lillypilly 91, 420 Lily-of-the-Valley 19, 26, 27, 28 limonene 43–5, 85, 87, 95, 313, 314, 316, 320, 327 linalol 44 linalool 30, 33, 43, 95 linalyl acetate 44 linarin 179 linoleic acid 34, 37, 118, 328 linolenic acid 34, 37, 118, 485 linolic acid 164 Lippia chevalieri 53 Liquorice 44, 75, 346 Listeria monocytogenes 104, 321 lithospermic acid 146 Lithospermum erythrorhizon 146 Litomosoides sigmodontis 281 littorine 390, 398 Liv-52 158 L-lysine 418 lobelaine 428 lobelanidine 427, 428 lobelanine 418, 428 Lobelia American Torch 423 Blue 423 Chinese 428, 430 Edging 423 Great Blue 426 Indian 424 Mexican 423 Pale-spike 426 Poison 429 Lobelia angulata 430 arenaria 430 arnhemiaca 423 cardinalis 425 chinensis 428, 429, 469 concolor 429 darlingensis 429 erinus 423 excelsa 424 inflata 418, 424–8, 431 laxiflora 423, 429 macrodon 430 membranacea 423 nicotianifolia 424, 425 nummularia 430 pedunculata 430 pratioides 429 purpurascens 429, 431 siphilitica 425, 426 spicata 426 tupa 423 lobelidine 425 lobeline 418, 424, 425, 428 Lobster Flower 103 Long Yam 444, 445

Lophomyrtus bullata 178 Lophophora williamsii 416 lovastatin 441, 443 Lucilia sericata 87 Luffa aegyptiaca 186 cylindrica 186 graveolens 186 lumbricin I 288 Lumbricus rubellus 288 terrestris 289 lumbrokinase 288 lunasin 473 lupanine 220, 417 lupeol 76, 171, 338, 481 lupinine 417 Lupins 415 lutein 85, 86, 142 luteolin 54, 56, 62, 65–7, 69, 70, 73, 76, 120, 171–3, 312, 325, 326, 429 luteolin 7-glucoside 76 luteolin 7-O-glucoside 65 Lycopersicon esculentum 455, 489 Lygodium flexuosum 186 japonicum 186 microphyllum 186 reticulatum 186 lysine 415, 417 M Ma Huang 12 Macaca mulatta 224 Macadamia integrifolia 135 Macrophomina 482 Macropus agilis 285 fuliginosus 285 giganteus 285 rufogriseus 285 Madagascar Periwinkle 10, 185 Madar 170 madasiatic acid 142 madecassic acid 140, 142, 143 madecassol 142, 149, 155 madecassoside 140, 142–4, 148, 149 Magic Ophthalmia cure 107 Makulu 163 malachite 205, 206, 207 Malaria 33, 57, 58, 87, 101, 102, 109, 111, 116, 134, 149, 153, 172, 185, 189, 201, 277, 287, 288, 336, 460–2 malic acid 32, 85 Mallotus mollissimus 187 philippensis 183 philippinensis 187 spp. 187 Mamane 416 Mandarin Orange 75 Mandragora autumnalis 344 caulescens 344 chinghaiensis 344 officinarum 342, 343, 359 turcomanica 344 Mandrake 342–6, 353, 358 Himalayan 344 True 359 Turkmenian 344 Mangifera

547 indica 148, 187 odorata 187 mangiferin 148, 185 Mango Ginger 159 Mangrove Black 182 River 182 Mangrove worm 267 mannitol 313, 314, 328 maokinine 13 Mapania microcephala 202 Marigold 78, 80, 81, 83, 85, 141 African 84, 85 Aztec 83, 84, 87 Corn 180 French 82–4 Marsilea drummondii 372 maslinic acid 37 Masto 301–3 Mastotermes darwiniensis 301–3 Matai 295 Matricaria chamomilla 66 recutita 66–8 matricarin 70 matricine 69 mekocyanin 19 Melaleuca leucadendra 187, 190 leucadendron 187 Melanthera biflora 60 integrifolia 60 Melia azedarach 184 Melicope elleryana 393 Melipona quadrifasciata anthidioides 55 Melissa officinalis 145, 178 Mentha arvensis 178, 179 canadensis var. piperascens 45 spicata 145, 178 x piperita 45, 145, 173. 178 menthofuran 45 menthol 45, 46 menthone 45, 320 menthyl acetate 45 Mescal Bean 416 mescaline 417 Mesquite 222 metahalloysite 215 metanicotine 396 meteloidine 351, 356, 370, 398 methicillin 207 methoxyeugenol 44 methoxyhydnocarpin 171 methyl anthranilate 44 bromide 116, 234 chavicol 84 eugenol 328 halide 234 thymol 104 methyleugenol 44, 316, 320 methylglucosinolate 115 mevinolins 443 Mexican Lobelia 423 Tarragon 84 Thyme 100 Yam 432, 433 Micrococcus flavus 334

548


luteus 205, 334 tetragenus 98 Microcyclus ulei 77 Microsporum 50, 56, 97 canis 103 gypseum 56, 97, 103, 335 Miliusa balanse 97 Milk Thistle 117, 129, 368 Milkweed 131 Milkwood 316 Milky Mangrove 131 Milky Plum 93, 94 Mimosa diplotricha 187 invisa 187 pigra 187 pudica 187 Mint, Variegated 99 miraxanthin V 122 Mirbelia oxylobiodes 135 mitchellene 317 mite honeybee 58 house dust 280 red spider 99, 116 scabies 322 mitomycin 201 Mock Strawberry 474, 475 Moluccella laevis 91 Momordica balsamina 187 charantia 178, 187 cochinchinensis 187 monacolin K 440, 441, 443, 444 monascin 441, 443 monascorubrin 444 Monascus pilosus 443 purpureus 441, 442 Monkshood 10, 212 monoamine oxidase 56 montera 375 montmorillonite 212, 221, 225–7, 271 Morinda citrifolia 135, 187, 467 spp. 187 umbellata 187 morphine 19, 21–3, 70, 149, 151, 152, 177, 192, 335, 341, 388, 394, 395 Mosqueta Rose 34 Moth, Diamondback 116, 300 Mountain Kangaroo Apple 454 Mountain Pratia 430 MRSA 36, 104, 134, 148, 155, 172, 179, 181, 192, 201, 202, 207, 321, 324, 334 Mud wasp 268 Mulga 426 multiflorin A 40 mumie 260 munumbicin 134, 201 muscaflavin 123 muscapurpurin 123 muscarubrin 123 muscovite 236 Mushroom Death Cap 368 Oyster 443 Termite 305 Mycobacterium africanum 175

avium 285 avium paratuberculosis 175,199 bovis 175, 176, 281, 285, 286 fortuitum 181, 183, 318, 324 indicus pranii 286 leprae 153, 155–8, 165, 170, 175, 278 lepromatosis 175, 278 marinum 202 microti 175 phlei 92 smegmatis 56, 176, 181, 183, 202, 324, 334 tuberculosis 55, 75, 104, 155, 159, 170, 174–6, 178, 182, 191, 201, 205, 334 ulcerans 175, 202–4, 286 myodesmone 311, 328 myoporone 300, 311, 316, 317, 328 Myoporum acuminatum 294, 327, 380 bontioides 295, 300 crassifolium 296 debile 292, 294 deserti 294, 300, 311, 321 floribundum 294 insulare 292, 293 laetum 178, 295, 296, 309, 312 montanum 294 parvifolium 293 petiolatum 294 platycarpum 308, 313 pubescens 296 sandwicense 294, 295 Slender 294 tenuifolium 295, 296 viscosum 294 myrcene 142, 313 Myriogyne minuta 105, 107, 108 Myristica fragrans 44 myristicin 43, 44 Myrmecobius fasciatus 303 Myrrh 75 myrtenal 108 myrtenol 108 myrtenyl acetate 108 myrtine 398 N N,N-dimethyltryptamine 417 N-alkylamides 57 narcotine 23 Nardoo 372 Nardostachys jatamansi 151 Nasturtium 86 Nasutitermes corniger 305 graveolus 302 triodiae 302 Native Box 123 Currant 464 Olive 123 Pepper 454 Ragwort 420 Thornapple 349, 350 Tobacco 372, 379, 402–4, 431 Necator americanus 274, 276, 280, 281 Neem 39, 164 Neisseria gonorrhoeae 113, 172, 472 meningitidis 75 Nelumbo nucifera 39

nematode 80, 87, 281 neohydnocarpin 170, 171 Neolitsea dealbata 135 neomycin 198 neoxanthin 142 nepetin 313 nepetoidin A 104 Nerium oleander 26, 212 nerol 29, 30, 31 nerolidol 44, 70 Ngaio 178, 295, 309, 312 ngaione 311, 312, 316, 327 niacin 130, 274 Nicotiana alata var. persica 411 amplexicaulis 407 benthamiana 405–7 bigelovii 410, 412 burbidgeae 407 cavicola 406, 407 debneyi 407 excelsior 403, 405, 407 fruticosa 410 glauca 405, 407, 409, 489 goodspeedii 405, 407 gossei 405, 407 heterantha 407 maritima 407 megalosiphon 406, 407 megalosiphon subsp. megalosiphon 406 occidentalis 406, 407 persica 410, 411 quadrivalvis 410 repanda 410 rosulata 408 rosulata subsp. ingulba 406 rotundifolia 409 rustica 406, 410–2 simulans 409 spp. 405 suaveolens 376, 389, 403, 404, 409 sylvestris 409 tabacum 403, 405, 406, 409, 410, 412, 422 tomentosa 411 truncata 409 umbratica 409 velutina 404, 405, 409 wuttkei 409 nicotine 227, 361, 366, 388, 389, 391, 395, 396, 398, 403, 404, 406, 407, 409, 410, 412, 414–6, 422, 425, 428 nicotinic acid 415 Nierembergia veitchii 489 Nigella sativa 320 Nightshade American 451, 464–6, 482–4 Black 451, 455, 464–6, 464–74, 483 Brazilian 451 Chinese Black 466 Felty 457 Green-berry 465 Silver-leaf 452 Spiny 452 Sticky 453, 470 Stinking 463 Velvet 461 White 474, 483 Woody 470, 472

Woolly 465 Nipple Fruit 460 Nippostrongylus brasiliensis 281 Nocardia asteroides 200 mediterranea 200 nonadecane 30, 31 noradrenaline 121, 325 noraporphine 177 noratropine 389 norcoridine 177 norepinephrine 12, 121 norharman 412 norhyoscyamine 389, 396, 398 nor-lobelaine 428 nornicotine 391, 395, 396, 398, 406, 407, 412, 415, 416 nor-wedelolactone 64 noscapine 22, 23 novocaine 371 Numbat 303 Nut, Betel 116, 372, 373, 392 Nutmeg 44 Nux Vomica 47 O Oak, Cork 393 Oak-leaf Thornapple 349 ocimene 85, 87 (Z)-β-ocimene 104 Ocimum sanctum 64, 178 scutellarioide 99 1-octen-3-ol 104 Odontotermes formosanus 268 oestradiol 123 oestrogen 434, 441 Oil Anise 42 Bastard Sandalwood 131 Bergamot 105 Bitter Orange 44 Bitter Orange Flower 44 Calendula 80 Camphor 43 Cardamomum 43 Celery Seed 105 Chaulmoogra 161, 162, 163, 164, 169, 170, 173 Cinnamon 43 Clove 43 Coriander 43 Dill 43 Eucalyptus 44, 46, 89, 90 Fennel 44 German Chamomile 67 Ginger 44 Hydnocarpus 169 Japanese Peppermint 45 Lemon 44 Nutmeg 44 Orange 41, 44 Oregano 105 Peppermint 45 Rose 29, 30, 31 Savin 105 Spanish Sage 105 Sweet Orange 44 Old Man Weed 105, 108 Oldenlandia diffusa 475 Oleander, Climbing 25, 449 oleandrin 337 oleanene 338 oleanolic acid 56, 80, 338

INDEX oleic acid 34, 118, 165, 328 Olibanum 75 Oligoceros haemorrhages 328 Onchocerca volvulus 454 Oncoba echinata 163 Oncomelania hupensis 109 Onion, Sea 26 opium 18–23, 109, 362, 370, 373, 388, 469, 470 Oplopanax horridus 178 japonicus 328 oplopanone 328 Orange 40, 42, 44, 488 Orange Cestrum 488 Orange oil 41, 44 Ordeal Bean 361 Oregano, Cuban 100 Oregano oil 105 Oreganum vulgare subsp. vulgare 105 ornithine 415 ouabain 25, 488 oxacillin 36 oxytocin 116, 435 P Pacific Yew 10 paclitaxel 447 Pademelon, Tasmanian 285 Paecilomyces varioti 335 palmatine 112 palmitic acid 34, 37, 118, 165, 328 paludolactone 56 palygorskite 215, 225, 228, 240 Pan troglodytes 262 Panax ginseng 444 notoginseng 474 Pandanus aquaticus 373 Pangium edule 168, 169 Papaver aculeatum 20, 21 argemone 20 dubium 20 horridum 21 hybridum 20 rhoeas 19, 20 somniferum 19, 20 somniferum subsp. setigerum 20 somniferum subsp. somniferum 20 papaverine 22, 69 paracetamol 57, 115, 227, 228 Paragonimus sp. 280 Paramphistomum cervi 149 paraquat 240 paregoric 20 parillin 450 Parmelia perlata 39 Parthenium argentatum 77 parvifloron 104 Pascalia glauca 61 Passiflora foetida 187 quadrangularis 421 spp. 187 patuletin 67, 78 Pediculus humanus 57 pelletierine 398, 417, 418 penicillin 11, 91, 191, 194–9, 202, 321 penicillinase 321 Penicillium 193, 194, 196, 198 camemberti 198

chrysogenum 195, 196, 197 glaucum 196 janczewskii 199 notatum 195, 196 roqueforti 198 Pennywort Brazilian 139 Large-leaf 138 Lawn Marsh 139 Whorled 139 Pentacoelium bontioides 297 pentacosane 30 pepino 483 Pepper, Black 417 Pepper Vine 112, 113 Peppermint 45, 145, 173, 178 Perionyx excavatus 288 Periploca graeca 449 nigrescens 449 Periwinkle, Madagascar 10, 185 Persian Rose 35 Persian Tobacco 410 Persoonia falcata 92, 93, 94 juniperina 92 pinifolia 92, 93 salicina 92 Peyote 416 phellandrene 43 Phellodendron amurense 474 phenyl ethyl alcohol 29 phillyrin 312 Pholidia scoparia 296 phosgenite 209, 210 Phyllanthus fraternus 64 niuri 64 phyllygenin 312 phyoxolin 108 Physalis angulata 187 spp. 187 Physostigma venenosum 361 physostigmine 359, 361–6, 368, 386, 449, 472 phytic acid 270 Phytolacca dodecandra 223 Phytophthora 482 piceine 317 Pigweed 118 Pimelea prostrata 131 Pimpinella anisum 42 pinene 43, 44, 314, 327 Pink Brownii 95 Pink Cauliflower 95 Pink-flowered Evodia 393 pinoresinol 312, 325 pinworm 280 Piper betle 372 nigrum 417 piperidine 415, 417 piperine 417 piperitenone 85, 87 Pitcherry 372 Pitchiri 372 Pithera 391 Pittosporum hirtellus 135 phylliraeoides var. microcarpa 135 tenuiflorum 178

Pituri 106, 318, 369, 370, 372–6, 378, 381, 383, 388, 391, 392, 395, 396, 398, 402–4, 406, 418, 420, 426, 431 Rock 405, 407 Sandhill 406, 408 Planchonia careya 135, 180, 181 Plantago ovata 480 plantolin 108 Plasmodium falciparum 87, 97, 102, 109, 116, 134, 172, 201 vivax 460 Platycodon grandiflorum 474 Plectonema boryanum 244 Plectranthus amboinicus 100, 101, 103, 104, 156 apreptus 100 argentatus 100 aromaticus 101 barbatus 100–4 coleoides 103–5 congestus 99 cylindraceus 103, 104 diversus 135 ecklonii 104 elegans 104 foetidus 100 forskohlii 101 fruticosus 103–5 grandidentatus 104 grandis 101, 104 graveolens 100 habrophyllus 135 heretoensis 104 incanus 104 laxiflorus 156 madagascariensis 99 melissoides 104 neochilus 103, 104 ornatus 103, 104 parviflorus 100 saccatus 99 scutellarioides 99 vetiveroides 102, 156 Pleuranthodium racemigerum 184 Pleurotus ostreatus 443 Plum, Brown 370, 371 Plum-tree, Native 316 Plutella xylostella 133, 300 Podargus strigoides 285 Podocarpus grayae 135 Pohutukawa 178 Poison Lobelia 429 Poison Pratia 429 poliumoside 315 Polyalthia australis 202 michaelii 202 nitidissima 202 patinata 202 polygalacic acid 50 Polygonum bistorta 446 Polysaccum olivaceum 250 Poporo 457 Poppy Bristle 20 Field 19, 20 Long-headed 20 Opium 19, 20, 21 Pale 20 Rough 20

549 Populeon 348 Poroporo 457 Portulaca bicolor 119 grandiflora 119, 122 oleracea 122, 123, 188 pilosa 119, 120 spp. 188 quadrifida 122 tuberosa 123 Potato 220, 221, 319, 455, 458 Potato Rose 32 Potato Tree 461 Pratia angulata 430 arenaria 430 Chatham Island 430 macrodon 430 Mountain 430 nummularia 430 pedunculata 430 Poison 429 Purple 429 White Star 430 Pratylenchus pratensis 87 Premna serratifolia 135 Presbytis rubicunda 262 Prezwalskia tangutica 359 Prickly Fanflower 377 procaine 371 progesterone 432, 433 Propionibacterium acnes 29, 205, 322 Propolis 55, 81 propyl gallate 128 proscillaridin 26 Prosopis juliflora 222 pallida 222 Prostanthera rotundifolia 135 prostigmin 363 prostratin 131, 134 Proteus vulgaris 56, 121 protocatachuic acid 306 protodioscin 440, 477 protoneodioscin 445 protoneogracillin 445 Provence Rose 38 Prumnopitys taxifolia 295 prunasin 311, 312, 317, 328 Prunella vulgaris 145, 446 Prunus sargentii 36 Psacalium compositum 329 decompositum 329 radulifolium 330 sinuatum 329 Pseudocanthotermes spiniger 305 Pseudocheirus peregrinus 204 Pseudomona fluorescens 98 Pseudomonas aeruginosa 29, 56, 75, 80, 121, 132, 148, 199, 202, 205, 206, 298, 321, 334, 337, 435 aureus 56 maltophilia IAM 1554 244 pyocyanea 92 Pseudopanax crassifolium 178 pseudopelletierine 418 psi-taraxasterol 81 psilocin 341 Psilocybe mexicana 341 Psoralea 374

550


Psoroptes cuniculi 87 Psydrax oleifolia 91 Psyllium 480 Pterigeron odorus 88 Pterocaulon alopecuroides 96, 97 balansae 96 glandulosum 96 globuliflorus 88 globulus 96 nivens 96 polystachyum 96, 97 redolens 96 serrulatum 88, 96, 420 sphacelatum 88, 96, 97, 135, 182, 324, 420 spheranthoides 96 verbascifolium 96 Pukatea 176, 177 pukateine 177 Pukeweed 424 pulegone 45 Punica granatum 418 Purple Pratia 429 Purslane 118–23 Pygmaeopremna herbacea 446 pyrazinamide 176 pyrethrin 300 pyrogallol-5–carboxaldehyde 37 pyromorphite 232, 272 pyrrolidine 415 Pythium ultimum 56, 201 Q Quaker Laudanum 20 quassinoid 172, 184 quercetin 35, 67, 69, 70, 97, 119, 120, 142, 313, 338, 356, 429 Quercus suber 393 quinine 220, 224, 341, 377, 388, 394, 460 R rabdosiin 146 radioiodine 240 Radium Weed 131 Radula marginata 191 radulifolin 330 Raillietina echinobothrida 149 Ramarama 178 Rauvolfia serpentina 10 Red Cestrum 487 Red Mold Dioscorea 441 Red Root Gromwell 146 Red Yeast Rice 440–4 Rescue Remedy 48, 111 Rhamnus cathartica 178 Rheum officinale 178 Rhizoctonia solani 56, 335 Rhodotorula rubra 56 Rhoeadine 19 Rhus javanica 36, 184 Rice, Red Yeast 440, 442, 443 Ricinus communis 188 rifampicin 160, 176 rifamycin 200 ringworm 102, 160, 187, 322, 347, 356, 382, 407, 459, 465 scalp 415 River Red Gum 190 Rock Isotome 424, 426, 427 Rock Pituri 405, 407 Roman Chamomile 66, 67, 68, 81 Rooibos tea 172 Rosa

arvensis 32 canina 32–7 centifolia 29, 35, 36, 38, 39 chinensis 29, 38 damascena 29, 30, 33–6, 38 davurica 33, 35 dumalis 33 eglanteria 29, 34, 36 gallica 29, 30 laevigata 33, 36, 38 micrantha 32–5 mollis 32 multiflora 29, 33, 35, 39, 40 pisiformis 33, 34 pulverulenta 33, 34 roxburghii 29, 33 rubiginosa 33, 34 rugosa 32, 35–8 sempervirens 33, 36 villosa 33, 34 rosamultin 36 Rose Cabbage 38 Cherokee 33, 38 Chestnut 29, 33 China 29 Damask 29, 30, 35 Dog 32 English Tea 33 Field 32 Mosqueta 34 Multiflora 33, 35, 39 Persian 35 Potato 32 Provence 38 Rose absolute 31 Rose oil 29, 30, 31 Rose Otto 31 Rose water 31 Rosehips 32, 33, 34 Rosemary 144, 145 rosmarinic acid 51, 102, 104, 143–6, 179 Rosmarinus officinalis 144 Ross River fever 203 roundworm 14, 165, 279, 337 American Racoon 275 Canine 276 Giant Intestinal 280 rubidomycin 201 rubixanthin 33 rubropunctatin 444 Rubus spp. 188 rufocromomycin 201 Russian Dandelion 70, 77 rutin 28, 128, 142, 330, 338 Ryparosa amplifolia 167 anterides 167 javanica 166, 167 kurrangii 166, 167, 168 kurzii 167 maculata 167 maycockii 167 milleri 167 sp. Daintree 167 wrayi 167 S sabinene 44, 316, 320 sabinyl acetate 104, 105 Saccharomyces cerevaceae 148 cerevisiae 195, 334

safrole 42–4, 177, 316, 320, 328 Sage 98, 145, 178 Chinese 146 oil, Spanish 105 Saguinus mystax 262 sakuranetin 338 Salacca zalacca 262 Salak 262 salbutamol 482 Salmonella enterica serovar. typhimurium 202 group C 56 paratyphi 56, 148 typhi 35, 36, 55, 56, 121, 148, 334, 465 typhimurium 35, 36, 132, 148, 298 salvanolic acid 146 Salvia chinensis 474, 475 lavandulifolia 105 miltiorrhiza 146, 475 officinalis 145, 178 Sambucus williamsii 325 Sandalwood Bastard 131, 294, 297–9, 306, 317 Red 298, 308 Sandhill Pituri 406, 408 Sanguinaria canadensis 178 Sanguisorba officinalis 178 santalcamphor 298, 300 Santalum acuminatum 299 cygnorum 298 lanceolatum 135 obtusifolium 393 Santolina chamaecyparissus 180 sapogenin 432, 433, 435, 439, 440, 447 Sapucainha 163, 173 Sarcina lutea 148 Sarcoptes scabiei 323 sarmentogenin 449 Sarsaparilla 482 sarsapogenin 448 sarsasapogenin 449, 450 Savin oil 105 SC-1, SC-2 482 scabies mite 322, 458 Scaevola spinescens 135, 377 Schinopsis balansae 220 Schinus molle 58 Schistosoma 109, 274, 283, 453 haematobium 280, 282 intercalatum 282 japonicum 282 mansoni 281–3, 483 mekongi 282 schistosomiasis 278, 282 schizanthines 390 Schizanthus grahamii 391 Scilla maritima 26, 27 scillaren 26 scillarin A 27 Scolopia braunii 135 scoparone 84, 429 scopolamine 341, 346, 349, 352, 354–6, 358, 359, 366, 370, 387, 389, 390, 395, 398–401, 463 scopolamine butylbromide 353 scopoletin 345, 356, 359, 483

Scopolia carniolica 359, 360 Japanese 360 japonica 359, 389 lurida 359, 360 podolica 360 tangutica 359 scopolin 356 Scute 287 Scutellaria baicalensis 287 barbata 475 Sea Onion 26 Sea Purslane 120 Senecio aegyptius var. discoideus 330 nemorensis. 330 spp. 330 sepiolite 225, 228, 271 sesquithuriferone 300 Sesuvium portulacastrum 120 Shan Yao 436, 441 Shepherd’s Purse 19, 185 Shigella 56, 75 boydii 56, 148 dysenteriae 56, 121, 148 flexnerii 148 sonnei 56 shilajit 260, 261 Sida cordifolia 188 silibinin 368 Silkworm 284 Silver-leaf Nightshade 452 Silybum marianum 117, 368 Singapore Daisy 60, 62, 138 Sisal 433, 447 sitosterol 65, 142, 459, 480, 483 Skullcap Barbat 474, 475 Chinese 287 smectite 202, 203, 215, 217, 221, 224, 227, 253, 263, 272, 273 Smelly Bush 88 smilagenin 450 Smilax 482 aristolochiaefolia 450 corbularia 446 glabra 446 regelii 482 Smyrnium olusatrum 71 Snakegourd 75 Snakeroot, Indian 10 Sneezeweed 105–8, 110, 420 Desert 105 Sneezewort, Australian 50 Snowdrop, Caucasian 364 sobatum 479 sodium aescinate 126 solacallinidine 454 sola-dunalinidine 454 solamargine 435, 453–5, 459, 460, 462, 465, 473, 476–8, 482–5 Solandra grandifolia 390 longifolia 389, 390 maxima 390 solanidine 455, 465 solanine 220, 341, 455, 460, 462, 463, 471, 472, 473, 479, 481, 489 solanogantine 485 Solanum aethiopicum 473 americanum 451, 464–6, 482–4

INDEX atriplicifolium 472 aviculare 452–7, 482 callium 454 capsiciforme 454 chrysotrichum 482, 484 crinitum 478 densevestitum 457 dulcamara 189, 455, 463, 464, 470–3 echinatum 490 eleagnifolium 452 ellipticum 420 erianthum 461, 462 fendleri 220 frutescens 472 giganteum 485 glaucophyllum 489 hispidum 482 incanum 452, 454, 472, 477, 482, 483 indicum 452 jamesii 220 khasianum 452 laciniatum 452, 453, 456 lasiocarpum 452 lasiophyllum 452 linnaeanum 475, 476 lycocarpum 453, 478, 483 lyratum 473–5, 483 macrocarpum 459 malacoxylon 489 mammosum 452, 460, 461 marginatum 452, 486 mauritianum 420, 421, 456 melongena 451, 455, 472, 473, 476, 477, 489 muricatum 477 niger 482 nigrescens 482, 484 nigrum 158, 341, 451, 453, 455, 462–6, 468, 469, 472–5, 482, 483 nigrum var. americanum 467, 472 nigrum var. humile 464 nigrum var. villosum 453 nodiflorum 472 nudum 460 opacum 463, 465 paludosum 452, 470 paniculatum 466, 485 photeinocarpum 466 platanifolium 452 pseudocapsicum 478 quadriloculatum 452 racemosum 472 rostratum 451, 452 scabrum 468 scolentum 472 seaforthianum 451 sisymbriifolium 453, 472, 477 sodomaeum 478 surattense 483 torvum 458, 459, 460, 470, 474, 483, 485 trilobatum 452, 478, 479 tuberosum 189, 220, 342, 455 valdiviense 472 variabile 466 villosum 465 virginianum 472 wrightii 451 xanthocarpum 481, 482, 483 solasodine 447, 452–6, 459–62, 465, 470, 471, 473, 476, 479, 481, 482,

489 solasonine 454, 455, 459, 462, 465, 473, 476, 478, 482–4 solatriose 460 Solenostemon scutellarioides 99 Solidago arguta 180 canadensis 180 Sonchus arvensis 446 Sophora chrysophylla 416 japonica 128 secundiflora 416 tonkinensis 446 Sparassis crispa 474 sparteine 220, 417 spathulenol 70, 300, 313, 318, 328 Spearmint 145, 178 Sphagneticola trilobata 57, 60, 62 Spiderflower 117 Yellow 114 Spilanthes acmella 52, 53, 55–8 acmella var. oleracea 56 alba 56 americana 56 calva 56–8 ciliata 57 grandiflora 52 mauritiana 52, 55, 56, 58 ocymifolia 56 oleracea 52, 53, 55–7 paniculata 53, 56, 58 uliginosa 55 spilanthol 52, 53, 56–8 Spinach 86, 122, 241, 344, 464 Spinacia oleracea 344 Spinifex Hard 269 Lobed 269 Soft 269 Spinifex triodia 268 spiroethers 69 Spodoptera littoralis 99 litura 164 spongolite 253 Squill 26, 27 St Anthony’s fire 73 St John’s Wort 186 St Mary’s Thistle 158 Staphyloccoccus aureus 29, 36, 54–75, 80, 91, 97, 101, 103, 109, 121, 124, 148, 155, 171, 172, 179, 191, 192, 194, 202, 204–7, 298, 321, 322, 334, 337, 471 aureus haemolyticus 191 epidermidis 56, 471, 321 Star Anise 42 stearic acid 34, 118 Stellaria spp. 189 Stemodia grossa 135 lythrifolia 420 viscosa 88 Stemphylium solani 103 Stenochilus glaber 297 Stephania tetrandra 148 Sticky Nightshade 453, 470 stigmasterol 56, 65, 142, 150, 435, 443, 445, 448, 479, 480 Stink Bug 337 Stinking Nightshade 463

Stinking Roger 86, 87, 88, 189 Stramonium 19, 340, 349, 351–3, 357, 358, 384 Strawberry, Mock 474, 475 Streptococcus aureus 75, 205 faecalis 459 haemolyticus 56 mutans 54, 104, 205 pneumoniae 75, 174, 321, 322 pyogenes 322, 334, 471 sanguinis 205, 282 sobrinus 104 Streptoglossa bubakii 88 decurrens 88 odora 88 streptokinase 288 Streptomyces aureofaciens 198 caespitosus 201 chrysomallus 200 coerulorubidus 201 erythreus 199 griseus 198 mediterranei 200 nodosus 200 parvullus 200 peucetius 201 rufocromogenes 201 venezuelae 197 verticillus 201 streptomycin 174, 185, 198, 445, 460, 471 strophanthin 25, 449 Strophanthus gratus 25, 449 kombe 26, 485 Strychnos toxifera 362 Succory 73 Sugarwood 308, 309 sulphur 47 Summer Adonis 25 Sunflower, Beach 53, 56, 59–61, 156 Sunflower Daisy 59, 61 Swainsona 418 swainsonine 418 Sweet Flag 151 Sweetbriar 29 Sweetweed 319 Symonanthus aromaticus 398 Symphytum 51 officinale 120 officinalis 51 Syncerus caffer caffer 262 Syzygium 189, 420 aromaticum 36, 37, 43, 319 australe 135 jambos 178 luehmannii 135 smithii 91 T tabacine 412 tabacinine 412 Tacca chantrieri 446 cheancer 446 leontopetaloides 446 plantaginea 446 subflaellaea 446 Taenia saginata 280 solium 280

551 Tagetes erecta 39, 83–87 filifolia 83, 87 glandulifera 87 lucida 83, 84, 87 minuta 83–7, 189 patula 82–7, 141 rupestris 87 subulata 87 tagetone 85, 87 Tai-fung-tze 163 Tamarillo 452 Tamarix gallica 158 Tanacetum ligulatum 320 Tangerine 75 tapeworm 29, 183, 280, 281 Taraktogeno kurzii 163, 165 Taraxacum albidum 75 aristum 70 coreanum 75, 76 cygnorum 70 formosanum 75 hepaticolor 70 japonicum 75, 76 khatoonae 70 kok-saghyz 70, 77 mongolicum 70, 74, 75, 76 officinale 64, 70, 74, 76, 158, 189 platycarpum 70, 74, 76 sinicum 74 squamulosum 70 taraxasterol 76 taraxerol 76 taraxinic acid 76 Tarragon, Mexican 84 Tasmannia lanceolata 135 Taxus baccata 10 brevifolia 447 canadensis 178 tellimagrandin I 36 teloidine 398 Tephroli 64 Tephrosia purpurea 64 Teredo novalis 267 teriloside 300 termilone 38 Terminalia arjuna 158 belerica 151 chebula 37, 64, 151 ferdinandiana 135 terminolic acid 143 termite 244, 262, 265–9, 275, 300–5, 328, 339 Cathedral 302 Harvester 304 Magnetic 302, 304 Termitomyces albuminosus 305 clypeatus 306 eurirrhizus 306 heimii 306 microcarpus 306 mummiformis 306 reticulatus 305 terpineol 43 4-terpineol 320 terpinolene 85, 320 terpinyl acetate 43, 316 Terra Sigillata 211, 212, 213, 253, 254, 255, 286

552


testosterone 102, 434 tetracycline 36, 195, 198, 227, 228, 238 tetramethylputrescine 398 tetrandrine 148 Tetranychus urticae 99, 135 tetraphyllin 165 Teucrium argutum 100 chamaedrys 178 thalictrine 112 Thalictrum foliolosum 112 thankunic acid 143 thankuniside 143 THC 191, 192 thebaine 22 thiamin 274 Thornapple Common 350 Desert 349 Downy 350 Fierce 350 Hairy 350 Native 349, 350 Oak-leaf 349 Thottea grandiflora 202 Thyme 29, 67, 144, 145, 150, 173 Mexican 100 thymol 101, 104, 108, 109 Thymus vulgaris 145 Tick, Australian Paralysis 412 Tickweed 114, 115, 116, 117 tigloidine 396, 398 tigogenin 447, 449 Tinea capitis 415 Tinospora cordifolia 151 smilacina 135 tiotropium bromide 360 Tobacco 381, 405, 407, 409, 410, 412–6, 418–20, 423, 456, 489 Australian 404 Latakia 411 Native 372, 379, 402–4, 431 Persian 410 Shiraz 411 Turkish 84, 410, 411 Velvet 409 Wild 106, 403, 406, 411, 420, 425–7 Woodland 409 tocopherol 31, 32 tokorogenin 435 tomatidenol 455 tomatidine 454, 455, 461, 479 Tomato 86, 116, 221, 291, 455, 485 Toredo navalis 419 tormentic acid 35 Torreya nucifera 328 Toxocara canis 275, 276 cati 275 Toxoplasma gondii 283, 284 trans,trans-arnesol 70 trans-anethole 44 trans-caryophyllene 104 trans-humulone 333 trans-nerolidol 44 trans-tiliroside 38 trans-β-farnesene 142 Traveller’s Joy 110, 111 trematodes 280, 282 tremolite 226, 236

Treponema pallidum pallidum 472 pallidum pertenue 472 Trichilia roka 113 rubescens 223 Trichinella spiralis 281 Trichodesma zeylanicum 420 Trichophyton mentagrophytes 55, 56, 97 rubrum 56, 97, 103, 335 Trichosanthes kirilowii 75 Trichosurus vulpecula 176, 204 Trichuris suis 280, 281 trichiura 280 vulpis 276 tricosane 30 Trigonella foenum-graecum 448, 450 trihydroxybenzaldehyde (TBA) 37 Trillium spp. 448 Triodia basedowii 269 pungens 268, 269 Triphala 151 Trisetum flavescens 489 triterpene 81, 318, 398 tropisetron 359 troxerutin 128 Trypanosoma brucei 282, 382 cruzi 54, 57, 483 tubocurarine 362 Turkey Berry 458 Turmeric 156, 158, 159, 443 Turpentine Tree 370 Tuvaraka 163 U ulcer Bairnsdale 203 Buruli 203 Daintree 203 umbelliferone 67, 69 undecanal 101 Upright Virgin’s Bower 111 Urginea maritima 26 scilla 27 urokinase 288 ursolic acid 35, 37, 144, 190, 398, 422 Urtica 47 V Vaccinium myrtillus 385 Valeriana officinalis 179 wallichii 151 valtropine 390 vancomycin 321, 324, 445 vanillin 43 Vanillosmopsis erythropappa 67 Varanus gouldii flavirufus 256 Varroa destructor 58 Velvet Nightshade 461 Velvet Tobacco 409 veratridine 485 veratrine 485 Veratrum 485, 486, 487 album 486, 487 nigrum 486 verbascoside 313, 315, 325, 326, 328

Verbascum thapsus 81 verbenone 327 vermiculite 205 Vernonia kotschyana 474 Verticordia brownii 95 plumosa 95 verticordina 95 V-Gel 39 Viannia braziliensis 54 Vibrio cholera 217 cholerae 84, 148 mimicus 56, 148 parahaemolyticus 56, 148 Vigna spp. 189 vincristine 10, 149, 171, 341 violaxanthin 142 Virgin’s Bower 112 viridiflorene 300 viridiflorol 45, 82, 300 virus, Ross River 203 Vitex agnus-castus 297 negundo 39, 98 negundo var. cannabinifolia 98 trifoliata 98 vitexin 28 voleon U 101 Vombatus ursinus 285 Vomit-wort 429 W Wallaby Agile 285 Bennett’s 285 Wasp, mud 268 Waterbush 294, 380 wattle 373 Wattle 256 Umbrella 182 Wedelia asperrima 59, 61, 66 biflora 53, 56, 58, 60, 156 calendulacea 57, 63, 64 chinensis 56, 57, 58, 63, 65, 66 glauca 58, 61 longipes 59 paludosa 54–57 parviceps 57 spilanthoides 59, 60 stirlingii 60 subvaginata 57 trilobata 54–7, 60, 62 urticifolia 60 verbesinoides 60 wedelolactone 63–66 wedeloside 61, 66 wedelosin 57 Weevil, Cotton Boll 58 whipworm 271 Canine 276 Human 280, 281 pig 280 White Hellebore 486, 487 White Nightshade 474, 483 White Star Pratia 430 Whiteroot 429, 430, 431 Whitewood, Desert 306, 307 Wild Tobacco 106, 403–6, 411, 420, 425, 426, 457 Wild Tomato 420 Wild Yam 432–4 wilgi 267

Winter Adonis 19, 25, 26 Witchetty Grub 257 Withania somnifera 151, 158 Wolf Apple 478 Wolfsbane 10, 212 Wollastonia biflora 60 Wombat, Common 285 Woodbridge Poison 427 Woodland Tobacco 409 Woody Nightshade 470, 472 Woolly Nightshade 465 Woolly Rattlepod 92 worm American boll 337 Asian armyworm 164 Canine hookworm 276 Canine roundworm 276 Canine whipworm 276 Egyptian cotton leafworm 99 filarial 53, 153, 280, 282, 454, 477 flatworm 279, 280 giant intestinal roundworm 280 hookworm 14, 275, 276 human hookworm 280 human whipworm 280, 281 meadow eelworm 87 pig whipworm 280 pinworm 280 rat tapeworm 87, 281 roundworm 14, 165, 275, 279, 337 scalp ringworm 415 silkworm 284 tapeworm 280 threadworm 280 whipworm 271, 280 Wuchereria bancrofti 280 X xanthine 130 xanthine oxidase 130 Xie Bai 174 Xylosma terrae-reginae 135 Y Ya Dan Zi 172 Yam Air-Potato 436, 444, 445 Bitter 438, 439 Japanese 435, 437 Long 444, 445 Mexican 432, 433 Wild 432–4 yamogenin 448, 454 Yellow Jessamine 147 Yew, Pacific 447 yonogenin 435 Yucca brevifolia 449 Z zeaxanthin 33, 85 zeolite 205, 238–40, 242, 253 Zi Cao 146 Zingiber officinale 44 zingiberene 44 zingiberol 44 zizaene 327 zucchini 86

Medicinal Plants in Australia Volume 4

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