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Traditional, current and potential uses of Australian medicinal plants.

Abstract

Plants and plant extracts have been central to traditional medical practice since time immemorial. In addition to their use in the various traditions of herbal medicine that have arisen in every part of the world, plants remain the source of most of the effective drugs used in orthodox medicine. This paper outlines the history and current economic importance of Australian medicinal plants and examines the potential for future development.

Reference

Jones GL. Traditional, current and potential uses of Australian medicinal plants. Journal of the Australian Traditional-Medicine Society 2006;12(4):201-205. (33 references).

Keywords: Aboriginal medicine; Eucalyptus; Tea tree; Lemon myrtle; Duboisia; Eremophila.

Introduction

Plant-derived medicines have been part of traditional healthcare in most parts of the world and constitute an integral part of the human experience.

The earliest written record of medicinal usage of plants, the Chinese pharmacopoeia, appeared about 5,000 years ago. Some of the medicinal lore of other major population groups has been recorded in written form, although a lot of valuable information has been transferred in non-written ways through shamanistic initiation, ancestral example and tribal ritual.

Given the alarming rise of antibiotic resistance in bacteria and other organisms of medical importance, there is a continuing need for new and effective therapeutic agents. Historically, herbal extracts have provided the basis for much of contemporary orthodox pharmacology but now, more than ever, it is necessary to establish the scientific basis for any reported or observed therapeutic activities of such crude extracts with the aim of identifying novel molecular motifs that will form the basis of improved therapeutic regimes.

This article will describe various therapeutic activities of crude plant extracts, essential oils and purified molecules from Australian medicinal plants.

Aboriginal Medicine

Traditional medicine is still practised by tribal Aborigines in central and northern Australia and much of this knowledge has been documented (1). In most other areas of Australia the record is fragmentary or it has been lost irrevocably.

Limited research and reports of Aboriginal traditional medicine were first published in the mid to late nineteenth century (2). At one stage, all members of the Aboriginal family knew their medicinal plants, their location, structure, value and their application. The botanical knowledge committed to memory was comprehensive and essential for their survival. With no written language, they remembered the optimal seasonal time for selection, and the correct method of preparation and indications for use. Such knowledge was passed on through example and through tribal ritual involving song and dance (1).

Early colonial botanists described a wide variety of medicinal uses by Aboriginals of plants from the genera Eucalyptus, Melaleuca, Acacia and Eremophila among others, and early European settlers began to use several of the plants already in use by Aborigines as well as adapting plant extracts, particularly essential oils, to new purposes after comparison with their own European plants.

Perhaps the first Australian plant used medicinally by the British settlers was the Sydney peppermint (Eucalyptus piperita) probably because the crushed leaves are roughly redolent of the English peppermint (Mentha piperita) whose oil was used to treat colds and colic. The major component of the peppermint gum essential oil, piperitone, is only a minor component of English peppermint oil even though the two oils may have similar medicinal qualities (3).

Be this as it may, this steam distilled essential oil along with essential oils and kino from other Eucalyptus species were among the first exports of the colony of New South Wales to England. These early successes lead to a much greater interest in Australian medicinal plants in the nineteenth century leading to the discovery and use (often as tonic to aid digestion) of among others Sebacca orata, Alstonia constricta, Doryphora sassafras and Similax glyciphylla (3).

It is not my intention in this brief review to dwell on traditional medicinal usage since there are already a number of admirable publications in this area (4,5) but rather to give a brief summary of current usage of Australian medicinal plants as crude extracts, essential oils and pharmacological feedstock and examine the potential for future development in this regard.

Eucalyptus Oils

Eucalyptus oils are obtained by steam distillation of the leaves of Eucalyptus spp and have aromas characteristic of the particular species used. Depending on the taxonomic approach employed in their categorisation, there may be as many as 700 species of eucalyptus with many individual species displaying multiple chemotypes whereby the composition of the essential oil bears a direct relationship to the particular genetic variant. There is therefore an immense range in the percentage composition of the oil with usually only a few distinct aromatic molecules constituting the bulk of any given oil but with each oil having hundreds of minor constituents (6,7).

E. globulus, the best known variety for medicinal oil production, is the blue gum tree of Victoria and Tasmania where it attains a height of more than 110 metres ranking as one of the tallest trees in the world. It is also called the fever tree, being largely cultivated in unhealthy, low-lying or swampy districts for its antiseptic qualities and its ability to lower the water table. Baron Ferdinand von Muller, from 1857 to 1873 Director of the Botanical Gardens in Melbourne, made the qualities of Eucalyptus known all over the world, and so led to its introduction into Europe, North and South Africa, California and non-tropical districts of South America.

The medicinal oil whose useful properties reside largely in its 1,8 cineole content is commonly sold in pharmacies and general retail outlets or in the form of sprays, cough lollies and ointments or in formulation with other oils as a general purpose liniment designed to provide relief from muscular aches and pains. It may be used as an inhalant or chest rub to ease breathing difficulties, or as a disinfecting and soothing mouthwash in water.

Although it does have certain medicinal properties, the pleasant and 'healthy' flavour and fragrance of cineole-rich eucalyptus oil plays an important role of perception in their acceptance and widespread use. Acompound found in smaller amounts in the oils of many Eucalyptus, p-menthane-3.8-diol, is a biochemical pesticide. This active ingredient is used to make products that are applied to human skin and clothing for the purpose of repelling insects, such as mosquitoes.

The oil from the lemon scented gum Eucalyptus citriodora contains citrinellal, rather than cineole, as the major constituent. The oil is used in whole form for fragrance purposes, usually in the lower cost soaps, perfumes and disinfectants, but also as a source of citrinellal as feedstock for the chemical industry.

Several hundreds of species of Eucalyptus have been shown to contain volatile oil though, historically, fewer than 20 of these have been exploited commercially for global oil production (7). In Australia, the reduced level of oil production compared with several generations ago is a result of the inevitable rise in labour costs associated with production rather than a depletion of the trees.

In this context it should be noted that most eucalyptus respond well to coppicing. Coppicing is the deliberate harvest of most of the secondary branches and leaves to encourage thicker leaf growth at an appropriate harvest height for subsequent harvesting. The advent of mechanical harvesting coupled with newer agronomic approaches and the exploitation as plantation timber of species other than those of current and/or past commercial importance ensures the ongoing relevance of the Australian Eucalyptus oil industry.

Eucalyptus Resin

E. nostrata and some other species of Eucalyptus yield eucalyptus or red gum, a ruby-coloured exudation from the bark. Red gum is a very powerful astringent prepared in the form of tinctures, syrups, lozenges etc.

E. globulus, E. resinifera and other species yield what is known as Botany Bay kino, an astringent, dark-reddish, amorphous resin, which is obtained in a semi-fluid state by making incisions in the trunk of the tree and is used for similar purposes.

Formylated Phloroglucinol Compounds from Eucalyptus

Recently Foley and Lassak have reported on the potential of formylated phloroglucinol compounds (FPCs) from Eucalyptus spp which demonstrate a wide range of bioactivities including tumour suppression as well as antibacterial and antiviral properties (8).

Sideroxylonal C, isolated from the flowers of Eucalyptus albens, has been noted as a potent inhibitor of human plasminogen activator inhibitor type 1 (PAI-1) and therefore potentially useful in the treatment of thrombotic diseases (9).

Tea Tree Oil (TTO)

Many different plants of the genera Melaleuca and Leptospermum have been referred to as tea trees perhaps because of the brown colour they impart to water due largely to tannins in the bark.

Many of these plants also yield essential oils, although by far the most important of these from a commercial perspective is the oil from Melaleuca alternifolia (TTO) which in recent times has spawned an industry of global proportions.

The tree is a paperbark shrub whose native habitat is swampy coastal regions of northern NSW. The Bundjalong Aboriginal people of northern NSW were said to be aware of the healing powers of the Melaleuca leaves.

In 1923 AR Penfold at the then Technological Museum in Sydney discovered the high germicidal activity of the steam distilled essential oil and established that the activity was largely associated with terpinen-4-ol, the major component of one chemotype which is now grown commercially in northern NSW (10).

A different chemotype has a higher level of 1,8 cineol, the major component of many Eucalyptus oils (3). The germicidal properties of TTO led to its incorporation into Australian soldier's medical kits in World War II and into machine cutting oils in ammunition factories.

After the war the popularity of TTO began to wane but with a resurgence of interest in natural remedies during the 1970's and 1980's, the TTO industry moved into high gear as new uses were found. The broad spectrum antimicrobial activity of TTO had been confirmed by many authors (11).

The mechanism of action is relatively non-specific but this very non-specificity may be important in its demonstrated activity against antibiotic resistant bacteria (12). The oil has been used as an antibacterial in the treatment of acne and as a suggested topical antifungal in the treatment of onychomycosis (13), candiasis (14) and tinea (15). Its value as a mouthwash has been emphasised by recent studies on the susceptibility of oral bacteria (16), while its value as an inhalant is indicated in studies on the antibacterial activity against respiratory tract pathogens (17).

The oil also shows promise as a topical anti-inflammatory which, combined with its strong topical bactericidal and fungicidal activity, recommends it as an aid to accelerated wound healing (18). The oil shows promise as a topical antiviral agent (19).

The oils of several other Melaleuca spp notably quinquinervia (nerolidol, linalool and 1,8-cineole chemotypes) and ericifolia are also strongly bactericidal(20) and may find uses in the future whereas the oil of Melaleuca cajuputi (cajuput oil) containing 50-70% 1,8 cineol and 30% terpineol is known for its antispasmodic and antihelmintic properties (3).

Lemon Myrtle Oil

The tree Backhousia citriodora was named after the colonial botanist James Backhouse. The oil was first steam distilled from the leaves in 1890 by a German doctor who sent it back to Germany to be used in the essential oil industry. Schimmel & Co of Dresden carried out the first analysis of the oil observing an extremely high (90-97%) citral content.

In the early 20th century lemon myrtle was used in Australia as a source of citral-rich essential oil for culinary lemon flavouring and fragrance but was replaced by citral-rich oils distilled from lemon grass and litsea.

Again, the more recent global interest in natural products has seen a resurgence in the lemon myrtle industry currently promoting the use of the essential oil and strong smelling foliage and fruits of lemon myrtle in perfumes, food flavourings, confectionery, herbal teas and in aromatherapy, emphasising the rainforest origins of the species. Commercial plantations of lemon myrtle were established in the late 1990's and expansion of planting is expected as demand for the products grows.

Lemon myrtle oil has been noted to exhibit even higher antibacterial and antifungal activities than Melaleuca (tea tree) oils (20). Some caveats have been expressed however with regard to the widespread use of the neat oil as a topical agent largely due to the extent of its cytotoxicity against skin cells (21). Used as a 10% solution, lemon myrtle oil has demonstrated potential value in the treatment of molluscum contagiosum virus (MCV) in HIV negative children without any irritant effects (22). MCV is a very common skin lesion in HIV-positive individuals.

Aniseed Myrtle Oil

Another essential oil, useful in the food industry, is steam distilled from the leaves of the aniseed myrtle (Backhousia anisata, now known as Anethole anisata) which is indigenous to the subtropical rainforest of the Bellingen and Nambucca rivers in northern NSW.

Two chemotypes have been observed. Both the trans-e-anethole and methyl chavicol chemotypes have antifungal and antibacterial activity although the methyl chavicol chemotype may be carcinogenic in mice (20).

Australian Sandalwood Oil

Australian sandalwood oil is produced by steam distillation of the heart wood of the tree Santalum spicatum. The tree is a native of Western Australia occurring in medium to low rainfall areas from Carnarvon to north of Albany. Topically, the oil may be of use as an antibacterial and antifungal agent (23).

In particular, these properties combined with its mild sedative activity, its anti-inflammatory activity and its pleasant aroma indicate its medicinal as well as aesthetic value as an additive to massage oils (24).

The main components a and a santalols (also occurring in the closely related Indian sandalwood Santalum album) have been shown to act as potent antagonists of dopamine and 5-HT receptors (23). One of the components of S. spicatum not found in S. album, [alpha]-bisabolol, has been shown to block pathways leading to the formation of inflammatory leucotrienes and prostanoids (25).

Duboisia and other Solanaceae

The genus Duboisia is represented by three species, D. myoporoides (R. Br.), D. hopwoodii (F. Muell) and D. leichhardtii (F. Muell.), described by colonial botanists in 1802, 1861 and 1867 respectively. D. myoporoides is found mainly along the east coast of Australia in warmer areas of relatively high rainfall, whereas D. leichhardtii is restricted to a relatively small, drier inland region in south-east Queensland.

Around 1880, scopolamine and hyoscyamine were identified as the main active principles of pharmaceutical importance in leaves of D. myoporoides and D. leichhardtii and cultivars derived from selected crosses of these species are now plantation grown to provide the raw material for the drug Buscopan[R].

Duboisia hopwoodii, the pituri bush, was one of the most important plants of commerce among pre-contact Aboriginal people and complex trading routes existed which were well recognised across tribal boundaries. The plant was chewed with ash to aid in the extraction of the active alkaloids, chiefly nicotine (26). Whether or not Australian Aboriginals used the other Duboisia spp containing the tropane alkaloids (common psychoactive drugs in many other indigenous cultures) is a moot point (5).

Another Australian representative of the Solanaceae which has proved useful as a source of natural precursors for synthetic reactions in the pharmaceutical industry is kangaroo apple (Solanum laciniatum), which is endemic to temperate regions of south eastern Australia and New Zealand. The fruit and leaves are harvested as a source of solasodine, similar in structure to the diosgenins obtained from Dioscorea spp, and used like the diosgenins as a precursor for the synthesis of pharmaceutical steroidal hormones (27).

Current and Future Research in Australian Medicinal Plants

In the light of the relative paucity of knowledge concerning bioactive compounds extractable from Australia's rich and in many cases unique flora, and in recognition of the value of indigenous knowledge in this regard, a number of very recent scientific initiatives have arisen within Australia which will stimulate future research. One of the more interesting is the Plants for People program launched in early 2005 under the direction of Professors Louis Evans and Brian Cheers which is part of the Desert Knowledge Cooperative Research Centre (28).

A number of laboratories have recently identified bioactive compounds with medicinal potential from plants used traditionally by native Australians. Pennachio et al (29) have demonstrated bactericidal activities in the species Acacia auriculoformis and Acacia bivenosa whereas Li et al (30) have isolated several potent anti-inflammatory agents from extracts of Tinospora smilacina (Benth).

Currently in our laboratory we are actively engaged in the identification, purification and molecular characterisation of useful bioactive compounds from plants of the genus Eremophila which occur naturally only in Australia. We have identified two serrullatanes from E. duttonii with strong bactericidal activity (31).

Furthermore, we have identified two new chemotypes of E. longifolia, one of which produces an antifungal essential oil in particularly high yield (32). We have also demonstrated anticancer activity of some Eremophila extracts (33).

Oils produced from plantations of cultivars derived from these new chemotypes may prove to be useful natural products both as chemical feedstock in the fragrance and flavouring industries, and like tea tree and lemon myrtle oil as additives in the cosmetic/pharmaceutical industry thus providing the basis of a new export oriented agricultural industry while revegetating degraded mining and/or otherwise unusable marginal arid land.

Conclusion

The Australian medicinal plant industry has had an interesting past with much to look forward to in the future. Australia has more endemic flora species than any other country in the world and many of these species produce unusual and, in many cases, unique secondary metabolites.

Activity guided fractionation of plant extracts, particularly those selected on an ethnopharmacological basis, followed by molecular characterisation, will no doubt reveal hitherto unsuspected structural motifs with novel bioactive compounds.

Australia has a reputation for being a clean-green agricultural producer and this, coupled with the mystique associated with the oldest continuous Aboriginal human culture, has been successfully used to market medicinal products (particularly those used by the complementary health sector) worldwide. With the advent of further activity-led research, including areas mentioned in this article, the range of medicinal oils and ointments as well as personal care products from plantation grown Australian plants is likely to expand considerably.

References

(1) Barr A, Chapman J, Smith N, Beveridge M. Traditional bush medicines --An Aboriginal pharmacopoeia. Aboriginal Communities of the Northern Territory of Australia, 1988.

(2) Maiden JH. The useful native plants of Australia. Sydney: Turner and Henderson, 1889.

(3) Lassak EV, McCarthy T. Australian medicinal plants. Melbourne: Kew, 2001.

(4) Devansen DM. Traditional Aboriginal medicine practice in the Northern Territory. Paper presented at International Symposium on Traditional Medicine, 11-13 September 2000, Awaji island, Japan.

(5) Pearn J. Medical ethnobotany of Australia past and present. The Linnean 2005;21(4): 16-24.

(6) Coppen JJW, Hone GA. Eucalyptus and its leaf oils. An indexed bibliography. Chatham, UK: Natural Resources Institute, 1992.

(7) Boland DJ, Brophy JJ, House APN (eds). Eucalyptus leaf oils. Use, chemistry, distillation and marketing, Melbourne/Sydney: Inkata Press, 1991.

(8) Foley W, Lassak E. The potential of bioactive constituents of Eucalyptus foliage as non wood products form plantations. RIRDC Publication No. 04/154, 2004.

(9) Neve J, de Almeida Leone P, Carroll AR, Moni RW, Paczkowski NJ, Pierens G et al. Sideroxylonal C, a new inhibitor of human plasminogen inhibitor type-1, from the flowers of Eucalyptus albens. Journal of Natural Products. 1999;62:324-326.

(10) Penfold AR, Morrison FR. Bulletin No 14. Sydney: Technological Museum, 1946.

(11) Markham JL. Biological activity of tea tree oil. In Southwell I,Lowe R (eds). Tea tree, the genus Melaleuca. Amsterdam: Harwood Academic Publishers, 1999.

(12) Caelli M, Porteous J, Carson CF, Heller R, Riley TV. Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphyloccus aureus. Journal of Hospital Infection 2000;46(3):236-237.

(13) Syed TA, Qureshi ZA, Ali SM, Ahmad S, Admad SA. Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream. Tropical Medicine and International Health 1999;4(4):284-287.

(14) Ergin A, Arikan S. Comparison of microdilution and disc diffusion methods in assessing and the in vitro activity of fluconazole and Melaleuca alternifolia (tea tree) oil against vaginal Candida isolates. Journal of Chemotherapy 2002;14(5):465-472.

(15) Tong MM, Altman PM, Barnetson RS. Tea tree oil in the treatment of tinea pedis. Australasian Journal of Dermatology 1992;33(3): 145-149.

(16) Takarada K, Kimizuka R, Takahashi N, Honma K, Okuda K, Kato TA. A comparison of the antibacterial efficacies of essential oils against oral pathogens. Oral Microbiology and Immunology 2004;19(1):61-64.

(17) Inouye S, Takizawa T,Yamaguchi H. Antibacterial activity of essential oils and their major constituents against respiratory tract pathogens by gaseous contact. Journal of Antimicrobial Chemotherapy 2001;47:565-573.

(18) Koh KJ, Pearce AL, Marshman G, Finlay-Joens JJ, Hart PH. Tea tree oil reduces histamine-induced skin inflammation. British Journal of Dermatology 2002;147(6):1212-1217.

(19) Schnitzler P, Schon K, Reichling J. Antiviral activity of Australian tea tree oil and eucalyptus oil against herpes simplex virus in cell culture. Pharmazie 2001;56(4):343-347.

(20) Wilkinson JM, Cavanagh HMA. Antibacterial activity of essential oils from Australian native plants. Phytotherapy Res 2005;19:643-646.

(21) Hayes AJ, Markovic B. Toxicity of Australian essential oil Backhousia citrodora (lemon myrtle). Part 2. Absorption and histopathology following application to human skin. Food and Chemical Toxicology 2003;40:1409-1416.

(22) Burke BE, Baillie JE, Olson RD. Essential oil of Australian lemon myrtle (Backhousia citriodora) in the treatment of molluscum contagiosum in children. Biomedicine and Pharmacotherapy 2004;58(4):245-247.

(23) Leach D, Myers S, Lin D, Markham J, Alderson S, McPhie K. Efficacy testing on sandalwood oils. Southern Cross University, NSW: Australian Phytochemicals Ltd, 2001.

(24) Okugawa H, Ueda R. Effects of sesquiterpenoids from "Oriental Incenses" on acetic acid induced--writhing and [D.sub.2] and 5-[HT.sub.2a] receptors in rat brain. Phytomedicine 2000;7(5):417-422.

(25) Torrado S. Effect of dissolution profile and (-)--[alpha]--bisabolol on the gastrotoxicity of acetylsalicylic acid. Pharmazie 1995;50:141-143.

(26) Latz P. Bushfires and bushtucker--Aboriginal plant use in Central Australia. Alice Springs: IAD Publishing, 1995.

(27) Bradley V, Collins DJ, Crabbe PG, Eastwood FW, Irvine MC, Swan, JM, Symon DE. A survey of Australian Solanum plants for potentially useful sources of solasodine. Australian Journal of Botany 1978;26:723-754.

(28) Pyper W. Plants for people. Ecos 2005;123:22-25.

(29) Pennachio M, KempAS, Taylor RP, Wickens KM, Kienow L. Interesting biological activities from plants traditionally used by native Australians. Journal of Ethnopharmacology 2005;96:597-601.

(30) Li RW, Leach DN, Myers SP, Leach GJ, Lin GD, Brushett DJ, Waterman PG. Anti-inflammatory activity,cytotoxicity and active compounds of Tinospora smilacina Benth. Phytotherapy Research 2004;18:78-83.

(31) Smith J, Jones G, Watson K. Isolation and identification of antimicrobial compounds from the Australian medicinal plant Eremophila duttonii (Scrophulariaceae) P407, 53rd Annual Congress of the Gesellschaft fur Arzneipflanzenforschung (GA) and joint congress with the Societa Italiana di Fitochimica (SIF). 21-25 August 2005, Florence.

(32) Smith J, Jones G, Watson K. Characterisation and evaluation of antibacterial activity of a new type of essential oil from Eremophila longifolia. P415, 53rd Annual Congress of the Gesellschaft fur Arzneipflanzenforschung (GA) and joint congress with the Societa Italiana di Fitochimica (SIF). 21-25 August 2005, Florence.

(33) Mijajlovic S, Smith J, Watson K, Parsons P, Jones GL. Traditional Australian medicinal plants: screening for activity against human cancer cell lines. J Aust Trad-Med Soc 2006;12(3):129-132.

Graham Lloyd Jones BSc (Hons) PhD is Associate Professor and convenor of Human Biology at the University of New England. He is responsible for the teaching of Human Biology to science, nursing and health science students and is particularly involved in bridging the gap between orthodox and complementary approaches to medicine and health. His research interests include mechanisms of action of antioxidants, stress proteins in the biology of human ageing and recently the identification of bioactive components of traditional Australian medicinal plants.

Address: Human Biology, School BBMS University of New England, Armidale NSW 2351. Telephone: (02) 6773 3274, email: gjones2@une.edu.au.
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