Pharmacognosy

Pharmacognosy is the study of medicines from natural sources. The American Society of Pharmacognosy^[1] defines pharmacognosy as "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources".

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Introduction

The word "Pharmacognosy" derives from the Greek words pharmakon (drug), and gnosis or knowledge. The term pharmacognosy was used for the first time by the Austrian physician Schmidt in 1811. Originally - during the 19th century and the beginning of the 20th century - pharmacognosy was used to define the branch of medicine or of commodity sciences ("Warenkunde" in German), which dealt with drugs in their crude, or unprepared, form. A "crude drug" means a dried unprepared natural material of plant, animal or mineral origin, which is used for medicine. The term "Pharmakognosie" and it discipline developed in German speaking areas of Europe - where it is a synonym of "Drogenkunde" ("science of the crude drugs").

Even though most of the pharmacognostic studies are focused on medicinal plants/herbal medicines, also other organisms are regarded pharmacognostically interesting. Particularly this is true for different types of microbes, i.e. bacteria and fungi. More recently, also many marine organisms have become targets of pharmacognostic studies.

Pharmacognosy is interdisciplinary, drawing from a broad spectrum of biological and even socio-scientific subjects: botany, ethnobotany, marine biology, microbiology, herbal medicine, chemistry (phytochemistry), pharmacology, pharmaceutics, clinical pharmacy and pharmacy practice related to the evaluation and clinical uses of medicines from natural sources, as well as their implications in health care management and public health.

The different fields within today's pharmacognosy include

• Medical Ethnobotany; study of the traditional use of plants in the society.
• Ethnopharmacology; study of the bio-pharmacological evalution of traditionally used natural drugs.
• Phytotherapy; study of effect of extracts from medicinal plants.
• Phytochemistry, or natural product chemistry; a field closely related to organic chemistry, studying the chemical composition of living organisms. It is also closely connected to the process of finding new drug candidates from natural sources.

Ethnopharmacology

When studying the effectiveness of herbal medicines and other nature-derived remedies, the information of the traditional uses of certain extracts of even extract combinations plays a key role. The lack of studies proving the use of herbs in traditional care is especially an issue in the United States where the use of herbal medicine has fallen out of use since the Second World War and was considered suspect since the Flexner Report of 1910 led to the closing of the eclectic medical schools where botanical medicine was exclusively practiced. This is further complicated by most herbal studies in the latter part of the 20th Century having been published in languages other than English such as German, Dutch, Chinese, Japanese, Korean and Farsi. As it may be more difficult to review foreign language publications, many of these publications have undergone been incorporated into the US Food and Drug Administration's "FDA" determinations of drug safety. In 1994 the US Congress passed the Dietary Supplement Health and Education Act (DSHEA), regulating labeling and sales of herbs and other supplements. Most of the 2000 US companies making herbal or natural products^[2] choose to market their products as food supplements that do not require substantial testing.

Issues in Phytotherapy

The part of pharmacognosy focusing on use of crude extracts or semi-pure mixtures originating from nature, namely phytotherapy, is probably the best known and also the most debated area in pharmacognosy. Although phytotherapy is sometimes connected to alternative medicine, when critically conducted, it may be considered the scientific study on the effects and clinical use of herbal medicines.

Constituents and Drug Synergyism

One characteristic of crude drug material is that constituents may have an opposite, moderating or enhancing effect. Hence, the final effect of any crude drug material will be a product of the interactions between the constituents and the effect of each constituent on its own. To effectively study the existance and affect of such interactions, scientific studies must examine the affect that multiple constitutents, given concurrently, have on the system. Herbalists assert that as phytopharmaceuticals rely upon synergy for their activities, plants with high levels of active constituents like ginsenosides or hypericin may not correlate with the strength of the herbs. In phytopharmaceutical or herbal medicine, the therapeutic effects of herbs cannot be determined unless its active ingredient or cofactors are identified or the herb is adminsistered as a whole. One way manufacturers have attempted to indicate strength is to engage in standardization to a marker compound. Companies use different markers, or different levels of the same markers, or different methods of testing for marker compounds. Many herbalists believe that the active ingredient in a plant is the plant itself.^[3]

Herb and Drug Interactions

The Sloan Kettering Memorial Cancer Center stated, in a review of a Juice product, which had been marketed as preventing cancer, that antioxidants could theoretically interfere with chemotherapy. ^[4] A recent review of the effect of antioxidants on chemotherapy, however, found no evidence for any deleterious effects of antioxidants on chemotherapy. ^[5] A study of herb drug interactions indicated that the vast majority of drug interactions occurred in four classes of drugs, the chief class being blood thinners, but also including protease inhibitors, cardiac glycosides and certain antibiotics like cyclosporin.Cyclosporin is not an antibiotic it is an immuno-suppressant ^{[6] [7]}

The major herbs that have caused interactions include St. Johns Wort, which will counteract immunosupressive drugs and interfere with digoxin and protease inhibitors. A complete list can be found at: http://www.herbological.com/images/SJW_table.pdf. The constituents of garlic, peppermint and milk thistle have been shown to have effects on the CYP3A4 enzymes in vitro, but it is not clear whether these constitutents will have the same effect in vivo (humans). ^[8]

Natural products chemistry

Instead of studying compound mixtures (crude extract or partially purified, eg. by fractionation), this aspect of pharmacognosy concentrates on isolated, pure compounds originating from nature. Most bioactive compounds of natural origin are secondary metabolites, i.e. species-specific chemical agents that can be grouped into various categories^{[citation needed]}. A typical protocol to isolate a pure chemical agent from natural origin is bioassay-guided fractionation, meaning step-by-step separation of extracted components based on differences in their physicochemical properties, and assessing the biological activity, followed by next round of separation and assaying. The most common means for separation is high-performance liquid chromatography (HPLC), but other chromatographical methods, such as thin-layer chromatography (TLC) are also used for these preparative purposes. After isolation of a pure substance, the task of elucidating its chemical structure can be addressed. For this purpose, the most powerful methodologies available are nuclear magnetic resonance spectroscopy (NMR) and mass spectroscopy (MS)^{[citation needed]}.

Loss of Biodiversity

Island Press, 1997: 131-163. Farnsworth for example, has found that 25% of all prescriptions dispensed from community pharmacies in the United States from l959 to l980 contained active ingredients extracted from higher plants. A much higher percentage is found in the developing world. As many as 80% of all people living in developing countries, or roughly two thirds of the world's population, rely almost exclusively on traditional medicines using natural substances, mostly derived from plants.[citation needed]

Constituents of substances used by traditional healers, have been incoporated into modern medicine. Quinine, physostigmine, d-tubocurarine, pilocarpine and ephedrine, have been demonstrated to have active effects ^[9] Knowledge of traditional medicinal practices is fast disappearing, particularly in the Amazon, as native healers die out and are replaced by more modern medical practitioners. Botanists and pharmacologists are racing to learn these ancient practices^{[citation needed]}, which, like the forest plants they employ, are also endangered ^{[10][11] [12]}

A explanation for some species loss is habitat lost due to invasive species introduction. Herbalist David Winston has suggested that a high proportion of nonnative species seen as invasive (kudzu, Japanese knotweed, mimosa, lonicera, St. Johnswort and purple loosestrife) may be harvested for the domestic herbal medicine market.^[13]

Species extinction is not only due to habitat loss. Overharvesting of medicinal species of plants and animals also contributes to species loss. This is particularly notable in the matter of Traditional Chinese Medicine where crude drugs of plant and animal origin are used with increasing demand. People with a stake in TCM often seek chemical and biological alternatives to endangered species because they realize that plants and animals lost from the wild are also lost to medicine forever but different cultural attitudes bedevil conservation efforts^{[citation needed]}. Still conservation is not a new idea: Chinese advice against overexploitation of natural medicinal species dates from at least Mencius, a philosopher living in the 4th century BC^{[citation needed]}.

Cooperation between western conservationists and practitioners have been beset by cultural difficulties. Westerners may emphasise urgency in matters of conservation, while Chinese may wish for the products used in TCM to remain publically available. One repeated fallacy^{[citation needed]} is that rhinoceros horn is used as an aphrodisiac in TCM. It is, in fact, prescribed for fevers and convulsions by TCM practitioners. There are no peer-reviewed studies showing that this treatment is effective. ^[14] In 1995 representatives of the oriental medicine communities in Asia met with conservationists at a symposium in Hong Kong, organized by TRAFFIC. The two groups established a clear willingness to cooperate through dialogue and mutual understanding. This has led to several meetings, including the 1997 First International Symposium on Endangered Species Used in Traditional East Asian Medicine where China was among 136 nations to sign a formal resolution recognizing that the uncontrolled use of wild species in traditional medicine threatens their survival and the continuation of these medical practices. The resolution, drawn up by the UN Convention on International Trade in Endangered Species (CITES), aims to initiate new partnerships in conservation. ^[15]

Sustainable Sources of Plant and Animal Drugs

As species face loss of habitat or overharvesting, there have been new issues to deal with in sourcing crude drugs. These include changes to the herb from farming practices, substitution of species or other plants altogether, adulteration and cross-pollination issues. For instance, ginseng which is field farmed may have significant problems with fungus, making contamination with fungicides an issue. This may be remedied with woods grown programs, but they are insufficient to produce enough ginseng to meet demand. The wildcrafted echinacea, black cohosh and American ginseng often rely upon old growth root, often in excess of 50 years of age and it is not clear that younger stock will have the same pharmaceutical effect. ^[16]Black cohosh may be adulterated with the related Chinese actea species, which is not the same. Ginseng may be replaced by ginseniodes from Jiaogulan which has been stated to have a different effect than the full panax root.^[17]

The problem may be exacerbated by the growth of pills and capsules as the preferred method of ingesting medication as they are cheaper and more available than traditional, individually tailored prescriptions of raw medicinals but the contents are harder to track. Seahorses are a case in point: Seahorses once had to be of a certain size and quality before they were accepted by practitioners and consumers. But declining availability of the preferred large, pale and smooth seahorses has been offset by the shift towards prepackaged medicines, which make it possible for TCM merchants to sell previously unused juvenile, spiny and dark-coloured animals. Today almost a third of the seahorses sold in China are prepackaged. ^[18]

The farming of plant or animal species, used for medicinal purposes has caused difficulties. Rob Parry Jones and Amanda Vincent write:

• One solution is to farm medicinal animals and plants. Chinese officials have promoted this as a way of guaranteeing supplies as well as protecting endangered species. And there have been some successes—notably with plant species, such as American ginseng—which is used as a general tonic and for chronic coughs. Red deer, too, have for centuries been farmed for their antlers, which are used to treat impotence and general fatigue. But growing your own is not a universal panacea. Some plants grow so slowly that cultivation in not economically viable. Animals such as musk deer may be difficult to farm, and so generate little profit. Seahorses are difficult to feed and plagued by disease in captivity. Other species cannot be cultivated at all. Even when it works, farming usually fails to match the scale of demand. Overall, cultivated TCM plants in China supply less than 20 per cent of the required 1.6 million tonnes per annum. Similarly, China's demand for animal products such as musk and pangolin scales far exceeds supply from captive-bred sources.

• Farming alone can never resolve conservation concerns, as government authorities and those who use Chinese medicine realise. For a start, consumers often prefer ingredients taken from the wild, believing them to be more potent. This is reflected in the price, with wild oriental ginseng fetching up to 32 times as much as cultivated plants. Then there are welfare concerns. Bear farming in China is particularly controversial. Around 7600 captive bears have their bile "milked" through tubes inserted into their gall bladders. The World Society for the Protection of Animals states that bear farming is surrounded by "appalling levels of cruelty and neglect" ^[19]. Chinese officials state that 10 000 wild bears would need to be killed each year to produce as much bile, making bear farming the more desirable option. The World society for the Protection of Animals, however, states that "it is commonly believed in China that the bile from a wild bear is the most potent, and so farming bears for their bile cannot replace the demand for the product extracted from wild animals".

• One alternative to farming involves replacing medical ingredients from threatened species with manufactured chemical compounds. In general, this sort of substitution is difficult to achieve because the active ingredient is often not known. In addition, most TCM users believe that TCM compounds may act synergistically so several ingredients may interact to give the required effect. Thus TCM users often people prefer the wild source. Tauro ursodeoxycholic acid, the active ingredient of bear bile, can be synthesised and is used by some Western doctors to treat gallstones, but many TCM consumers reject it as being inferior to the natural substance from wild animals.^[20]

See also

• Ethnobotany
• Ethnopharmacy
• Phytochemistry
• Phytotherapy
• Natural product drug discovery

References

1. ^ http://www.phcog.org/definition.html
2. ^ http://wfcinc.com/
3. ^ 1992, American Herbalism edited by Michael Tierra Crossings Press
4. ^ http://www.mskcc.org/mskcc/html/69270.cfm
5. ^ [1]Simone CB 2nd, Simone NL, Simone V, Simone CB. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1.Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8.
6. ^ Butterweek, Derendorf, et al PHARMACOKINETIC HERB-DRUG INTERACTIONS: Are Preventive Screenings Necessary and Appropriate. Planta Medica 2004:70:784-791
7. ^ http://www.thieme-connect.com/ejournals/abstract/plantamedica/doi/10.1055/s-2004-827223;jsessionid=17BD2009F2F6E0FC5E561C68A4545B6C.jvm2
8. ^ http://www.pjonline.com/pdf/cpd/pj_20030125_herbal10.pdf
9. ^ Farnsworth NR, Akerele O, Bingel AS, et al. Medicinal plants in therapy. Bull World Health Organ 1985; 63: 965-981
10. ^ Farnsworth, NR. The role of ethnopharmacology in drug development. In: Anonymous. , editor. Bioactive Compounds from Plants. Ciba Foundation Symposium 154. Wiley Interscience, New York; 1990.
11. ^ Farnsworth NR. Screening plants for new medicines. Wilson EO, Peters FM, editors. Biodiversity. Washington DC: National Academy Press, 1988: 83-97.
12. ^ Balick, MJ. Ethnobotany and the identification of therapeutic agents from the rainforest. In: Anonymous. , editor. Bioactive Compounds from Plants. Ciba Foundation Symposium 154. Wiley Interscience, New York; 1990. pp. 22–31.
13. ^ [2]David Winston. American Extra Pharmacopoeia
14. ^ Chinese Herbal Medicine: Materia Medica, Third Edition by Dan Bensky, Steven Clavey, Erich Stoger, and Andrew Gamble. Sep 2004
15. ^ [3]Can we tame wild medicine? To save a rare species, Western conservationists may have to make their peace with traditional Chinese medicine. Rob Parry-Jones and Amanda Vincent New Scientist vol 157 issue 2115 - 03 January 98, page 26
16. ^ http://www.rrreading.com/files/Life%20Span%20of%20Medicinal%20Plants.pdf
17. ^ Jialiu Liu and Michael Blumert. JiaogulanTorchlight Publishing. 1999,
18. ^ http://seahorse.fisheries.ubc.ca/pdfs/parryjones_and_vincent1998_newscientist.html
19. ^ http://www.animalsvoice.com/PAGES/writes/editorial/features/misc/bearbile_wspa1.html
20. ^ http://seahorse.fisheries.ubc.ca/pdfs/parryjones_and_vincent1998_newscientist.html