Natural products as drugs: Although Pharmacognosy is an interdisciplinary science that includes drugs obtained from plants, animals and microorganisms, the natural products with the broadest range of therapeutic application are currently obtained from the plant kingdom. Numerous familiar examples of plant derived substances with a broad therapeutic range can be given. Scopolamine and atropine among the more commonly used drugs in modern medicine are obtained from the nightshade family, Solanaceae. Several species of Datura and Atropa, contain these substances which are toxic when consumed in large quantities but are invaluable medicinal agents when taken in proper amounts. The Chibcha Indians of South America, used Datura species to sedate their human sacrifices, while in Africa a similar species was used in initiation rites. The juice of belladonna (Italian for beautiful lady), an Atropa species, was used by women centuries ago to dilate the pupils of the eyes, a sign of beauty in those days. Scopolamine and its derivatives are used in modern medicine to induce sleep and relieve gastrointestinal spasms; atropine and its derivatives are used today to dilate the pupils of the eyes by an ophthalmologist during an eye exam.
The Indian snakeroot belonging to the dogbane family, Apocynaceae, is obtained from Rauvolfia serpentina. It has been used in indigenous medicine for treating mental illness and insomnia. Its usefulness in modern medicine to treat hypertension and psychiatric disorders came to light with the isolation of the active principle reserpine. In a way it heralded the era of modern day antipsychotic agents. Also from the same family, the Madagascar periwinkle, which belongs to the species Catharanthus roseus, was investigated as a potential anti-diabetic agent. The plant extracts had some blood-sugar-reducing activity but also produced leucopenia, or an abnormally low number of white blood cells, in laboratory animals. Further investigation revealed that the active principles vinblastine and vincristine were useful in treating Hodgkin’s disease and childhood leukemia, respectively. In recent years, several semi-synthetic derivatives of these compounds have come on the market as anticancer agents.
In the last century, important compounds were also discovered and isolated from the animal kingdom. When minute amounts of hormones were isolated from glands of domesticated animals, their potential as useful medicinal agents became apparent but the cost of isolating larger amounts was phenomenally high. This led to a search for similar compounds in the plant kingdom. The search led to precursors such diosgenin found in certain yams belonging to the genus Dioscorea. Diosgenin and other steroidal compounds from plants are now used as starting materials in the production of hormone derivatives including the birth control pill.
Interesting and useful natural compounds have also been obtained from microbial sources. The drug LSD (lysergic acid diethylamide) is chemically related to useful medicinal agents found in the fungus ergot. A series of compounds found in ergot have been used to treat migraine headaches, help contract the uterus at term, stop postpartum hemorrhage and treat Parkinson’s disease among others. Other fungi and bacteria have helped produce a variety of antibiotics to treat infectious diseases. A category of soil bacteria, Actinomycetes, has provided us with more commercially useful antibiotics than any other group of microorganism.
Natural compounds such as morphine and codeine are obtained from opium. Synthetic compounds such as methadone with analgesic properties are often prepared using morphine as a prototype. Often, the synthetic or semi-synthetic derivatives have a better pharmacological profile and are more potent. Oxymorphone a semi-synthetic derivative of morphine is several times more active than the parent compound in relieving pain. The antibiotic erythromycin isolated from the cultures of Saccharopolyspora erythreus is labile but its semi-synthetic derivative clarithromycin is stable and active against a larger number of pathogens. Tinkering with the natural compounds has other advantages; a natural compound is more difficult to patent than a synthetic or semi-synthetic compound. In addition royalties from the patents help pay for further research and development of useful drugs.
Future of natural product research: In the last few years, microbial metabolites have become the mainstay of pharmaceutical natural product research. If microbial products are so good, why should we study plants? Literature research suggests that as a rule, microbes and plants don’t produce the same kinds of pharmacologically active compounds. Products from plants and microbes complement each other and provide a greater variety of chemically diverse compounds necessary for pharmacological research. Also, with the rapid rate of habitat destruction and species extinction we are witnessing at the moment, we are faced with, in essence, a now-or-never situation. Besides, with the acculturation of indigenous people, the knowledge of plant medicine they have derived over millennia is disappearing even faster than the plants themselves. The study of traditional medicine often referred to as ethnopharmacology has provided us with new drugs time and again. The new anti-malarial, artemisinin, was isolated recently from Artemisia annua an herb used in traditional Chinese medicine for over a thousand years.
Biotechnology is also an up-and-coming field. It involves technological application that uses biological systems, living organisms, or derivatives thereof, to make and modify products or processes for specific use. As natural resources start to dwindle, man will have to use cells of living organisms or enzymes from cells to produce products of medicinal value. Products from plant cell cultures is no longer is no longer a dream, it is reality. For example, the Japanese have commercially produced a red cosmetic dye, shikonin, from the plant cell cultures of Lithospermum erythrorhizon and berberine, an anti-microbial astringent, from the cultures of Coptis japonica. In recent years, combinatorial chemistry has provided a powerful synthetic tool in which huge numbers of structurally related compounds are produced for biological testing. Natural products are also amenable to combinatorial approaches by genetic manipulation of systems responsible for biosynthesis of promising natural drugs. Genetic engineering and combinatorial technologies together may represent one of the most promising future areas of pharmacognostic research.
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