Chapter 4 Biological and geographical sources of drugs

Current estimates of the number of species of flowering plants range between 200 000 and 250 000 in some 300 families and 10 500 genera. Despite a rapidly expanding literature on phytochemistry, only a small percentage of the total species has been examined chemically, and there is a large field for future research.

However, man did not require the modern methods of investigation to collect for himself a materia medica of plants which he often used in conjunction with magical and other ritual practices. Such folk medicines naturally varied according to the plants available in a particular climatic area and can be studied today in those more or less undisturbed primitive societies which still exist. It is interesting to reflect that such collections of herbal medicines compiled over centuries by trial and error, and presumably using the patient as the experimental animal throughout, must surely contain some material worthy of further investigation and should not be too readily discarded. Is it not also possible that those materials producing adverse reactions, one of the principal problems in the introduction of new drugs, might also have been eliminated by such a system of development?

In the current search for new drugs having, for example, antitumour or hypotensive activity the plants involved, unlike many of the more traditional medicaments, very often show no immediate indications of pharmacological activity. Investigators are thus faced with the problem of making a systematic investigation from among the thousands of species still unexamined. One obvious line of approach is to start with folk medicines of the world on the assumption that these materials have already been subjected to some human screening, however crude, and found acceptable to those cultures that use them. For many areas of the world, the plants used in folklore have been adequately recorded; but for other regions—for example, in South America, with its vast flora of potentially useful plants—the art of folk medicine in aboriginal societies is in rapid decline owing to a changing mode of life of the people. Ethnobotanists are currently fighting a battle against time to record such information before, within a generation or so, it is lost and with it a possible short cut to some medicinally useful plant. However, the urgency is well-recognized and as described in Chapter 8, the biological and geographical sources of many traditional plant remedies are being actively researched and documented. Often, successful research on a particular drug prompts the investigation of related species indigenous elsewhere, as evidenced with Hypericum and Taxus; the same is now happening with the bee product propolis. Much recorded information still requires sifting. An example of the employment of a combination of literature surveys and data from other sources in the search for new drugs is the US National Cancer Institute’s screening of thousands of plant extracts for antineoplastic and cytotoxic activity. This undertaking involves the team-work of botanists, phytochemists, pharmacologists and clinicians. In the absence of such sophisticated collaboration, much useful research by one discipline fails to be followed through to a utilitarian conclusion.

An inspection of the plant or plant-derived drugs included in western pharmacopoeias shows them to be composed of those which have survived from Greek and Roman eras, including some spices, those more characteristic of our own flora (e.g. digitalis) and introduced at a later date, other pharmacologically active drugs (e.g. cinchona—quinine— and ipecacuanha) added as a result of increased travel and colonial expansion, drugs (e.g. rauwolfia—reserpine) long used in other systems of medicine but of more recent introduction into Western medicine, and finally, recently discovered plant constituents of therapeutic value (e.g. vinblastine and vincristine from Catharanthus roseus) and those semisynthetic products (e.g. steroidal hormones) which depend on plant sources for starting material.

A perusal of the current literature soon reveals that, with the general availability of sophisticated methods of phytochemical analysis and pharmacological screening, together with the establishment of research centres, many traditional remedies not previously considered by Western scientists are being investigated in their countries of origin.

An examination of the list of drugs derived from natural sources, as included in any pharmacopoeia, indicates that the majority are derived from the Spermatophyta—the dominant seedbearing plants of the land. Within the Spermatophyta the number of species and the number of useful medicinal plants is divided unevenly between the phyla Gymnospermae, which yields some useful oils, resins and the alkaloid ephedrine, and the Angiospermae, which is divided into Monocotyledons and Dicotyledons (both of these provide many useful drugs but especially the Dicotyledons). Of the other divisions of the plant kingdom, the fungi provide a number of useful drugs, especially antibiotics, and are important in pharmacy in a number of other ways. The algae are a source of a limited number of drugs (e.g. agar and alginic acid), but the full pharmacological importance of this large group of aquatic plants has still to be realized. At the moment, lichens and mosses contribute little to medicine and the Pteridophytes are pharmaceutically best-known for the taenicidal ferns and lycopodium. Land animals provide such traditional pharmaceutical materials as gelatin, wool fat, beeswax and cochineal, and are a source of hormones, vitamins and sera. Among the many important pharmaceutical aspects of the Bacteriophyta are the production of antibiotics, their use in effecting various chemical conversions of added substrates and their employment in genetic engineering as, for example, in the production of human insulin and the transformation of higher plant cells by incorporation of part of the DNA of a bacterial plastid into the plant genome.

Researchers in the US have genetically engineered microbes to produce a precursor of the antimalarial artemisinin, which is then chemically manipulated to give the bioequivalent drug. It is hoped to have the product available for distribution by 2010 (report by K. Purcell, HerbalGram, 2006, 69, 24). This would alleviate the shortage, and high cost, of natural artemesinin, which is currently derived from the Chinese Artemisia annua (Chenopodiaceae).