plant medicines as a source of new drugs

Chapter 8 Traditional plant medicines as a source of new drugs





DEFINITION


The scientific study of traditional plant medicines can be considered as a major part of ethnopharmacology, a term that was only introduced in 1967 but which describes an approach to the discovery of single biologically active molecules that has been used ever since the first compounds were isolated from plant material. Ethnopharmacology can be defined as the scientific study of materials used by ethnic and cultural groups as ‘medicines’; in most instances, this is synonymous with the study of traditional medicines. These are usually the flowering plants, and so in most cases ethnopharmacology can be considered as a branch of ethnobotany: the study of the uses of plants by ethnic groups. However, it should be noted that some cultures, e.g. traditional Chinese medicine (TCM), also make use of animal and mineral matter, and so ethnopharmacology would also encompass the study of these.


Some discussion has taken place concerning the boundaries of what is meant by ‘ethnic’. Some would include all ethnically based systems outside Western scientific medicine but the balance of opinion probably rests on a more restrictive definition, which includes only those bodies of knowledge that are restricted to a group that has lived in a locality for a long period of time but that does not have a sophisticated theoretical framework, formal education and a documented written history. This more rigid definition excludes the medical systems that have developed over thousands of years in cultures based in China and the Indian subcontinent, and emphasizes small ethnic groups where there is a threat of the rapid loss of knowledge due to globalization, loss of habitat migration and other factors that might lead to loss of cultural distinctiveness.


Some ethnographers would distinguish between folklore and ethnopharmacology, claiming that the former is common knowledge in the population as a whole, largely concerning remedies for minor conditions, based on relatively innocuous material. Ethnopharmacology is more concerned with the knowledge of a few specialists who are regarded by the society as able to correctly diagnose and treat disease states, generally using more potent products. In many situations, these specialists are also linked with the religious practices of the society.


It should also be noted that the discovery of new drugs might derive from a wider use of plants than for strictly medical purposes alone. Thus materials used as poisons, in pest control, in agriculture, as cosmetics, in fermentation processes and for religious purposes might also yield active substances that can be exploited as leads for drug development. It can thus be seen that ethnopharmacology is a very interdisciplinary subject and any thorough investigation will probably need the input of a variety of specialists, such as anthropologists, botanists, chemists and pharmacologists.



HISTORICAL DIMENSION


The isolation of some of the opium alkaloids in the early nineteenth century was a key event in the development of modern pharmacy. It showed that isolated compounds had much the same activity as the existing ethnopharmacological material and so paved the way for current orthodox Western medicine, which uses pure compounds for treatment. Since then, a vast amount of money has been spent on the synthesis of novel compounds but also on the isolation of molecules from natural sources and their development into medicines. The contribution of traditional plant medicines to this process has been significant and some notable examples are shown in Table 8.1.



It should also be remembered that the active molecules isolated from traditional medicinal plants might not only provide valuable drugs butare also valuable as ‘lead molecules’, which might be modified chemically or serve as a template for the design of synthetic molecules incorporating the pharmacophore responsible for the activity. Examples of drugs having this origin are shown in Table 8.2.



Although the term ‘drug discovery’ is generally used to refer to the isolation of molecules with activity, it should also be remembered that there is increasing interest and recognition that a ‘drug treatment’ might consist of a mixture of compounds. This has always been the case for plant extracts (and most other natural substances), which contain several ‘active ingredients’. It should be noted that such extracts, usually based on a reputed traditional use somewhere in the world, are being introduced and increasingly used as a complementary therapeutic approach in the West. A selection of common ones, together with their ethnopharmacological roots, is shown in Table 8.3.



Scientific interest in ethnopharmacology has increased over the last few years and this is reflected in the formation of the International Society for Ethnopharmacology in 1990 and the European Society for Ethnopharmacology at about the same time. Both of these groups hold regular meetings. Several scientific journals also publish papers on this topic, notably the Journal of Ethnopharmacology, founded in 1979. The 100th volume of this journal, published in 2005, contains many useful ‘state of the art’ reviews on various aspects of ethnopharmacology.


This scientific interest is reflected by wider Western society, with its fascination with a much wider range of aspects of other cultures (e.g. dress, music, food, philosophy, as well as medicines) and this has been catalysed by large population migrations to the West and the relative ease of exposure to exotic cultures, which has been facilitated by large-scale international travel.


Although primarily concerned with human aspects, there has been a recent upsurge of interest in veterinary ethnopharmacology, i.e. methods and materials used to treat animals, particularly those important to the local economy as providers of food, transport and fibres. Other expansions from a strict definition of ethnopharmacology as being the study of medical practices include aspects of plants and other materials used in the diet, those used for ritualistic purposes, for poisons of various types, as cosmetics and as adjuncts to social gatherings. The increasingly blurred distinction between food and medicine, which has become a notable feature in ‘Western’ society, is a situation that has always been the case in other medical systems, such as Ayurveda and TCM, and it is now widely recognized that particular plants comprise part of the regular diet as much as for health maintenance as fortheir macronutritional properties. Attention has also been focused on the ways in which the role of a substance can change through time or as it is transferred from one culture to another. Thus, coffee was thought of as primarily medicinal when it was first introduced into northwest Europe in the seventeenth century, but quite rapidly became a beverage. It is also of interest that cultural restraints might minimize abuse of a substance in its indigenous context but that, when these restraints are removed as the plant begins to be used in another part of the world or society, it becomes a problem to that society. An example of this situation is seen with the abuse of kava-kava in Australia by aboriginal peoples, who do not have the framework of ritualistic use of these roots in the Pacific islands of Fiji and Tonga, where it originates.


Several recent surveys have shown that using ethnopharmacology as a basis of selecting species for screening results in a significant increase in the ‘hit rate’ for the discovery of novel active compounds compared with random collection of samples. It should be noted that several ‘classical’ drugs stated to have derived from ethnopharmacological investigations, e.g. several shown in Table 8.1, arise from plants known as poisons rather than those with a more ‘gentle’ action, which comprise the bulk of many herbal medicine species. The latter group often relies on a mixture of compounds with a mixture of activities, where synergism and polyvalence might be occurring, and where the isolation of one ‘active constituent’ is much less likely.


With a very large number of living organisms still awaiting scientific investigation (about 90% of the estimated 250,000 species of flowering plants, probably the most studied part of the biosphere), ethnopharmacology appears to offer a reasonable selective strategy to be considered in deciding which organisms to study. An interesting overview of some ethnopharmacologically based molecules and the problems involved in their gaining regulatory status was published recently (T. W. Corson and C. M. Crews, Cell, 2007, 130: 769–774).



THE PROCESS OF MODERN DRUG DISCOVERY USING ETHNOPHARMACOLOGY


The discovery process is composed of several stages. The first stage must be the reported use of a naturally occurring material for some purpose that can be related to a medical use. Consideration of the cultural practices associated with the material is important in deciding possible bases of the reputed activity. If there is an indication of a genuine effect, then the material needs to be identified and characterized according to scientific nomenclature. It can then be collected for experimental studies, usually comprising tests for relevant biological activity linked with isolation and determination of the structure of any chemicals present that might be responsible. The ‘active’ compounds are usually discovered by several cycles of fractionation of the extract linked with testing for the activity of each fraction, until pure compounds are isolated from the active fractions, a process known as bioassay-guided fractionation. These compounds, once their activity is proven and their molecular structure ascertained, serve as the leads for the development of clinically useful products. These various stages are discussed in detail below.



INFORMATION SOURCES


The most reliable type of information arises from in-depth studies carried out by field workers, living in the particular community of a particular ethnic group, on the use of the local plants and other materials. This usually comprises frequent communication with the local population, preferably in their own language. In should be noted, however, that an extensive knowledge of traditional medicines might reside with only a few people and a focus on this group would yield greater results. However, many such people are often reluctant to give away knowledge, which is regarded as ‘protected’ in some way, and this is exacerbated by concern that such knowledge could be exploited by drug companies, with little or no return to the original possessors of this knowledge.


Although the in-depth approach is most valuable, the fact is that most of the drugs that have been developed have arisen from less rigorous observations as a by-product of conquest or colonization. Thus, the more enlightened members of the Spanish conquistadores of Central and South America noted the practices of the various native American groups; and members of the British and French colonial administrations, together with non-governmental groups such as Christian missionaries, catalogued the uses of plants in Africa.


Most of these observations cannot now be checked in any way at first-hand, because the authors are long dead, but their records, books and other documents have been left as sources of information. This also applies to cultures that have left some type of written record, so that information on materials used in medicine in ancient Egypt, Babylonia, India and China is available. A recent paper (E. J. Buenz et al., Trends in Pharmacological Sciences, 2004 25: 494–498) describes some recent advances in electronic scanning of ancient texts that make information retrieval much easier, although the difficulties of linguistics and identifying the plants mentioned are not minimized as obstacles in such research.


Before such knowledge can be investigated scientifically, the information provided will often need clarification and translation into scientific terms. Of particular importance is the correct identification of the species used, which can be very difficult due to a lack of, or poor quality, illustrations as well as language difficulties. However, data on the part used, time of collection, methods of preparation, formulation and application are also necessary as they all affect the nature and amount of any biologically active compounds. Any restrictions on use due to time of year may be important, as they can indicate low levels (leading to inefficacy) or high levels (with concomitant risk of toxicity) of active compounds. Similarly, any types of individual excluded from treatment might indicate groups at risk due to age, gender or occupation.


Definition of the disease state in Western medical terms might also not be easy if the information is derived from a culture in which concepts of disease cause and symptoms are very different. In many records, the condition treated is described by a symptom that might be due to a number of disease states, e.g. a headache might be due to stress, tiredness, migraine attack or a brain tumour. Conversely, a particular disease state might be characterized by a number of symptoms, all of which have to be addressed when searching for possible leads to treating that illness. Thus, as an example, when searching an inventory of plants with a view to selecting those used for diabetes, those used for treating excess urination, weakness and ulcers should be considered, especially if diabetes is not recognized as a distinct illness diagnosed by sweet-tasting urine. Unfortunately, these factors are often ignored in current research, when a statement that ‘plant species X is used to treat illness Y by people living in Z’ is considered to provide adequate ethnopharmacological information. Such vague statements do not take into account all the possible sources of variation of biological activity that must be considered before any investigation proceeds.

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Jul 18, 2016 | Posted by in PHARMACY | Comments Off on plant medicines as a source of new drugs

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