Pharmacognosy

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Dioscorides’ Materia Medica, c. 1334 copy in Arabic, describes medicinal features of various plants.

Pharmacognosy is the study of medicines derived from natural sources. The American Society of Pharmacognosy 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."

Introduction

The word "pharmacognosy" is derived from the Greek words φάρμακον pharmakon (drug), and γνῶσις 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 commodity sciences (Warenkunde in German) which deals with drugs in their crude, or unprepared, form. Crude drugs are the dried, unprepared material of plant, animal or mineral origin, used for medicine. The study of these materials under the name pharmakognosie was first developed in German-speaking areas of Europe, while other language areas often used the older term materia medica taken from the works of Galen and Dioscorides. In German the term drogenkunde ("science of crude drugs") is also used synonymously.

Although most pharmacognostic studies focus on plants and medicines derived from plants, other types of organisms are also regarded as pharmacognostically interesting, in particular, various types of microbes (bacteria, fungi, etc.), and, recently, various marine organisms.

Pharmacognosy is interdisciplinary, drawing on a broad spectrum of biological and socio-scientific subjects, including botany, ethnobotany, medical anthropology, marine biology, microbiology, herbal medicine, chemistry, biotechnology, phytochemistry, pharmacology, pharmaceutics, clinical pharmacy and pharmacy practice. The contemporary study of pharmacognosy can be divided into the fields of

• medical ethnobotany: the study of the traditional use of plants for medicinal purposes;
• ethnopharmacology: the study of the pharmacological qualities of traditional medicinal substances;
• the study of phytotherapy (the medicinal use of plant extracts); and
• phytochemistry, the study of chemicals derived from plants (including the identification of new drug candidates derived from plant sources).
• Zoopharmacognosy, the process by which animals self-medicate, by selecting and using plants, soils, and insects to treat and prevent disease.
• Pharmcognosy-Biotechnology, the synthesis of natural bioactive molecules using biotechnology.
• Herbal interactions, the interactions of herbs with other drugs and body.
• Marine pharmacognosy, the study of chemicals derived from marine organisms.

Origin

The word pharmacognosy had its debut in the early 19th century to designate the discipline related to medicinal plants. It is derived from the Greek word pharmakon meaning “a drug” and gignosco meaning “to acquire a knowledge.”

Pharmacognosy appears again in 1815 in a small work by Crr. Anotheus Seydler entitled Analecta Pharmacognostica.

Pharmacognosy is closely related to botany and plant chemistry and indeed, both originated from the earlier scientific studies of medicinal plants.

As late as the beginning of the 20th century, the subject had developed mainly on the botanical side, being particularly concerned with the description and identification of drugs both in their whole state and in powder form. Such branches of pharmacognosy are still of fundamental importance, particularly for pharmacopoeial identification and quality control purposes, but rapid development in other areas has enormously expanded the subject.

At the 9th congress of Italian society of pharmacognosy it was stated that current return of phyto-therapy was clearly reflected by the increased market of such products. In 1998 the latest figures available for Europe, the total OTC market for herbal medicinal products reached a figure of $6 billion, with consumption for Germany of $2.5 billion, France $1.6 billion and Italy $600 million. In the US, where the use of herbal products has never been as prevalent as in continental Europe, the market for all herb sales reached a peak in 1998 of $700 billion. This welcomed the scientific investigation of a rigorous nature.

The plant kingdom still holds many species of plants containing substances of medicinal value which have yet to be discovered. Large numbers of plants are constantly being screened for their possible pharmacological value.

Ethnopharmacology

When studying the effectiveness of herbal medicines and other nature-derived remedies, information on the traditional uses of certain extracts or 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 treatment with herbal medicine has fallen out of use since the Second World War. Herbal medicine has also been considered suspect since the Flexner Report of 1910 led to the closing of the eclectic medical schools where botanical medicine was exclusively practiced. This situation 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 Persian. As it may be more difficult to review foreign language publications, much of the relevant information may be unavailable to English speaking scholars. Some of the important botanicals have been incorporated into the U.S. Food and Drug Administration (FDA) determinations of drug safety. In 1994, 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 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 existence and affect of such interactions, scientific studies must examine the effect that multiple constituents, 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.

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. A recent review of the effect of antioxidants on chemotherapy, however, found no evidence for any deleterious effects of antioxidants on chemotherapy. 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 the immuno-suppressant ciclosporin.

The major herbs that have caused interactions include St. Johns Wort, which will counteract immunosuppressive 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 constituents will have the same effect in vivo (humans).

Natural products chemistry

Most bioactive compounds of natural origin are secondary metabolites, i.e., species-specific chemical agents that can be grouped into various categories. 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. Typically, such work is initiated after a given crude drug formulation (typically prepared by solvent extraction of the natural material) is deemed "active" in a particular in vitro assay. If the end-goal of the work at hand is to identify which one(s) of the scores or hundreds of compounds are responsible for the observed in vitro activity, the path to that end is fairly straightforward: 1. fractionate the crude extract, e.g. by solvent partitioning or chromatography. 2. test the fractions thereby generated with in vitro assay. 3. repeat steps 1) and 2) until pure, active compounds are obtained. 4. determine structure(s) of active compound(s), typically by using spectroscopic methods. In vitro activity does not necessarily translate to activity in humans or other living systems. The most common means for fractionation are solvent-solvent partitioning and chromatographic techniques such as high-performance liquid chromatography (HPLC), medium-pressure liquid chromatography, "flash" chromatography, open-column chromatography, vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), with each technique being most appropriate for a given amount of starting material. Countercurrent chromatography (CCC) is particularly well-suited for bioassay-guided fractionation because, as an all-liquid separation technique, concern about irreversible loss or denaturation of active sample components is minimized. 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). In the case of drug discovery efforts, structure elucidation of all components that are active in vitro is typically the end goal. In the case of phytotherapy research, the investigator may use in vitro BAGF as a tool to identify pharmacologically interesting or important components of the crude drug. The work does not stop after structural identification of in vitro actives, however. The task of "dissecting and reassembling" the crude drug one active component at a time, in order to achieve a mechanistic understanding of how it works in phytotherapy, is quite daunting. This is because it is simply too difficult, from cost, time, regulatory, and even scientific perspectives, to study experimental fractions of the crude drug in humans. In vitro assays are therefore used to identify chemical components of the crude drug that may rationally be expected to have a given pharmacological effect in humans, and to provide a rational basis for standardization of a crude drug formulation to be tested in [and sold/marketed to] humans.

Loss of biodiversity

Farnsworth for example, has found that 25% of all prescriptions dispensed from community pharmacies in the United States from 1959 to 1980 contained active ingredients extracted from higher plants. In some countries in Asia and Africa 80% of the population relies on traditional medicine (including herbal medicine) for primary health care. Constituents of substances used by traditional healers, have rarely been incorporated into modern medicine. Quinine, physostigmine, d-tubocurarine, pilocarpine and ephedrine, have been demonstrated to have active effects 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, which, like the forest plants they employ, are also endangered

An 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.

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. 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.

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 publicly available. One repeated fallacy 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. 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.

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. 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.

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.

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" . 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.

External links

• American Society of Pharmacognosy
• GA/Society for Medicinal Plant Research
• ESCOP-European Scientific Cooperative on Phytotherapy
• International Society for Ethnopharmacology
• American Botanical Council
• Journal of Ethnobiology and Ethnomedicine
• Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London

References

ar:علم العقاقير zh:生药学