The Persian physician philosopher, Avicenna (980-1037 A.D) contributed much to sciences of pharmacy and medicine through works like Canon Medicine, which served as a text book for medical students for centuries. In modern days, plant – based medicines continue to play an essential role in health care. As per estimation of World Health Organization (WHO), approximately 80% of world’s population from developing countries rely mainly on traditional medicines, most of which are derived from plants for their primary health care. WHO has recently decided to catalogue and evaluate the safety and efficacy of these remedies? Plant products are also important in health care for remaining 20% population in developing countries and for those in industrialized countries as well.
Analysis of data in the United States from 1959 to 1980 indicates that about 25% prescription drugs contain plant extracts or active principles derived from plants. At least 119 chemical compounds derived from 90 plant species are important drugs currently in use in one or more countries. Of these 119, 74% were discovered during attempts to isolate active chemicals from plant used in traditicual medicines. Examples of Sudi plant based drugs in current use are given below based on a WHO document.
Caventou and Pelletier reported the isolation of antimalarial drug quinine from the bark of Cinchona species (e.g. C.
officinalis) in 1820. The bark had long been used by indigenous people of Amazon region for treatment of fevers and was introduced into Europe in early 1600s to treat malaria. Anti-malarial drugs, chlorquine and mefloquine were synthesized later on. Artemisinin Artemisia annua (Quinhaosu) yielded the agent artemisinin in 1985. It was used in treatment of fevers for more than 2000 years in traditional Chinese medicine. Its more soluble derivatives, artemether and art ether are currently in use against malaria, increasingly resistant to first line treatment with chloroquine and sulfadozine-pyrimethamine and are considered as most effective antimalarial agents avaliable on market today.
This opiate isolated in 1816 by Serturner from opium poppy, Papaver somniferum had been used as an analgesic for over 4000 years. By using the structure as a model, chemists subsequently developed a series of highly effective synthetic opiate analgesic agents.
Paclitaxel (Taxol Bristol-Myers Squibb):
Most significant drug discovered and developed through the U.S. National Cancer Institute’s Developmental Therapeutics and Clinical Trials Evaluation Programs is probably paclitaxel. This was isolated in 1969 as part of a broad plant screening programme, from bark of pacific yew tree (Taxus brevifolia).
In early clinical trials (1989), it was found to be effective for inducing remission in cases of advanced ovarian cancers. Since then, it has shown significant therapeutic benefit for other advanced malignancies including lung cancers, malignant melanomas, lymphomas and metastatic breast cancers. It has shown promise in preventing the smooth muscle cell proliferation that can block arteries opened by stents.
As its natural sources of supply could not be relied upon, paclitaxel and other toxoids have been produced by semisynthetic conversions of a precursor compound found in renewable yew tree needles.
Indigenous Knowledge and Medicinal Plants:
In Asia and Indian subcontinent, written records were kept about medicines. Knowledge about use of specific plant for treating diseases in South America was mostly passed on orally among indigenous peoples. Two examples of materials that are currently used in both the countries of origin and in west are given below:
This is a generic term for a group of arrow poisons from South America, first described by explorers such as, Sir Walter Raleigh dating from the end of 16th century; it took another 200 years before von Humboldt conducted a systematic search for botanical sources of curares. Some curares from eastern Amazonia are derived mostly from various plant species of the genus Strychnos.
Extracts from South American vine Chondodertdron are most common curares and as blocking agents were successfully employed in 1932 for treatment of tetanus muscle spasms and spastic disorders. Isolation of t-tubacurarine, the most active agent from C. tomentosum led to a number of synthetic and semisynthetic, reversible paralyzing agents, which are very widely, used in general surgery today to achieve deep muscle relaxation without using high doses of general anesthetics.
This is extracted from leaves of Pilocarpus jaborandi and is known in west as pilocarpine. Indians of northeast Brazil including Apinaye use it as a stimulant for lactation and as a diuretic. The active principle, pilocarpine, was first isolated in Brazil by Countinho in 1875 and is currently used medically to stimulate salivation following head and neck radiation treatments or in Sjogren’s syndrome and in treatment of open angle glaucoma.
Most diverse organisms on the planet are microbes. Less than 5% of all microbial flora have been investigated to date.
Micro-organisms present in most environments have barely been studied. Ordinary seawater contains more than 1000 microbes of multiple species per cubic centimeter. In one cubic centimeter of soil, more than 1000 different species of microbial flora have been found. Less than 5% of these are culturable using current techniques. A number of marine natural product chemists and molecular biologists have examined unexplored marine microbial world as a source for novel structures and pharmacologic activity. Microbes were an unappreciated resource for medicines, until the chemical identification of antibiotics, penicillin and streptomycin made in early 1940s. Discovery of antibiotics and their subsequent production in massive quantities has revolutionized the treatment of many infectious diseases.
Penicillins and Cephalosporins (B-lactam antibiotics):
In 1928, Alexander Fleming noticed that a fungus. Pencillium notatum that had contaminated one of his cultures of Staphylococcus bacteria killed the bacteria adjacent to it. A decade later, the systemic drug penicillin was developed. Over next several years, it proved to be a remarkable effective antibiotic for millions of patient. In late 1940s, initial reports of bacterial resistance due to destruction of antibiotic by microbes surfaced. Another group of P-lactam antibiotics, first isolated from fungus Cephalosporium acremonium was found to overcome these cases of resistance. Modification of basic nucleus of P- lactam structure with maintaining activity, medicinal chemists synthesized over 40,000 active P-lactam containing molecules, approximately 30 of which are currently in use.
Stimulated by the discovery of penicillin, Waksman and his co-workers investigated a number of tropical soil bacteria, actinomycetes for their antimicrobial properties. In 1944, they reported discovery of streptomycin, isolated from Streptomyces griseus that was highly effective against bacterium Mycobacterium tuberculosis. With advent of resistance in M. tuberculosis and in other microbes and with identification of bacterial resistance mechanisms by Davies and his colleagues in early 1970s, many semisynthetic variants of natural compounds were discovered. Aminolglycosides are still widely used in infectious disease treatment.
One of the oldest and most successfully used plant products is the powder from pyrethrum flowers, Chrysanthemum cinerariaefolium, originally native to Dalmatian Mountains in Croatia (major producers currently are Kenya. Uganda. Rwanda and Australia). Conventionally the natural products from pyrethrum flowers are referred to as pyrethrins.
“Pyrethroids” refer to insecticides that use pyrethrins as prototype structure. Pyrethroids act quickly on insects and do not concentrate in surface water. All decomposition products are of lower toxicity than parent compound.
Hence, toxic residues will accumulate and contaminate the environment.
Biologically active carbamates were used possibly in the 17th century in old calabar region of southeast Nigeria. The Effiks used to collect the beans from a plant, later named Physostlgma penenosum in order to subject prisoners to its toxic effects as a means of uncovering admission of guilt. In 1925, structure of active agent physostigmine was determined followed by synthesis in 1935. Subsequently, a large number of similar compounds were synthesized and shown to inhibit the enzyme acetylcholinesterase. This enzyme is essential to operation of muscles in all animals. These compounds cause rapid paralysis of insects, and frequently they are not lethal.
They are often used in combination with other products.
Native to India and Burma, neem tree is a member of mahogany family, Meliaceae and is known as margosa tree or Indian lilac, Azadirachta indica. It is a perennial species, requiring little maintenance for growing. It has been introduced to West Africa and other parts of world. Its insect control efficacy was first recognized by fact that locusts would swarm on A. indica tree but not feed. Extracts from seeds and leaves have insect control activity and can be used without further refinement. Active ingredients have also been isolated and formulated as commercial products.
Neem has been used for generations in India as a general antiseptic. No comprehensive toxicological data, however, is available.
Marine environment is also a source for insecticides. Nereistoxin is an insecticidal poison isolated from marine worm, Lumbrinereis brevicirra. Synthetic modification of nereistoxin has led to a family of agents (Cartap, bensultap, and thiocyclam) that have been developed as commercial insecticides and which are potent contact and stomach poisons for sucking and leaf biting insects.
Values of Natural products as Pharmaceutical:
Newman and Laird (1999) demonstrated that percentage of sales derived from natural products or related compounds ranged from 50% for Merck to 8% for Johnson and Johnson, while majority of companies falling between 15 and 30 %.
Companies were not included, unless they had at least one drug that sold for more than US $1 billion. This was a onetime study using only 1997 sales figures for drugs that sold more than US $1 billion in that year and that almost all of natural product derived drugs in this analysis were microbial in origin. It was not for another two years that the first plant derived drug, Taxol (R) arrived and broke sales figures of US$ 1 billion.
MAPs and traditional medicine:
Existence of traditional medicine depends on plant species diversity and related knowledge of their use. Both plant species and Traditional Knowledge (TK) are important to herbal medicine trade and pharmaceutical industry. Plant provides, raw materials and traditional knowledge offer prerequisite information (Tabuti et al„ 2003). India has one of the richest plant medical traditions in world.
There are around 25,000 effective plant based formulations used in folk medicine and known to rural communities in India. Over 1.5 million practitioners of traditional medicinal systems use medicinal plants in preventive, promotional and curative applications; while over 7800 medicinal drug manufacturing units in India consume about 2000 tonnes of herbs annually (Ramakrishnappa, 2002). Market for ayurvedic medicines is estimated to be expanding at 20% annually. Sales of medicinal plants have grown by nearly 25% in India in past ten years (1987-96), the highest rate of growth in world (Masood, 1997). But per capita expenditure in India on medicines per annum is amongst the lowest in world. Two of the largest users of medicinal plants are China and India. Traditional Chinese Medicine (TCM) uses over 5000 plant species while India uses about 7000.
International market for medicinal plant related trade is to the tune of US $ 60 billion having a growth rate of 7% per annum. China’s share in world Verbal market is US$6 billion, while India’s share is only US$1 billion, which is expected to rise to Rs. 3000 crores by 2005, (Rawat, 2002). TCM is projected to rise to US$400 billion by 2010 (Wang and Ren, 2002).
Traditional and folklore medicine handed on from generation to generation is rich in household remedies and community practice. According to an estimate of World Health Organization (WHO), nearly 80% of the populations of developing countries rely on traditional medicine, mostly plant drugs for their primary health care. Traditional medicine has served as a source of alternative medicine, new pharmaceuticals and healthcare products. Medicinal plant is important for pharmacological research and drug development.
Plant constituents are used directly as therapeutic agent and starting materials for synthesis of drugs or as models for pharmacologically active compounds (Mukherjee, 2003). A significant number of modern pharmaceutical drugs are thus based on or derived from medicinal plants. Derivatives of medicinal plant are non-narcotic with little or no side effects.
Prospects of Plant Based Medicines and Health Care Products:
Nearly three fourths of plant-derived prescription drugs used worldwide was discovered following leads from local medicine. About 25% of modern medicines are descended from traditionally used plants. Many other are synthetic analogues built on prototype compounds isolated from plants. Almost 70% modern medicines in India are derived from natural products (Choudhary, 2002). Basic uses of plant in medicine will continue in future as a source of therapeutic agents, and as raw material base for extraction of semi-synthetic chemical compounds such as cosmetics, perfumes and food industries.
Popularity of plant derived products has been traced to their increasing acceptance and use in cosmetic industry as well as to increasing public costs in daily maintenance of personal health and well being. Though efficacy of herbals requires development of quality consciousness in respect of evaluation related evidences, supplying the demand for botanicals and herbals is a booming business (Mnkherjee, 2002). Recently, even developed countries are using medicinal systems that involve use of herbal drugs and remedies. Undoubtedly, the demand for plant derived products has increased worldwide. Demand is estimated to grow in the years to come, fuelled by growth of sales of herbal supplements. Scientists, doctors and pharmaceutical companies will be looking at countries like china. India etc.
for their requirements as they have most number of medicinal plant species and are top exporters of medicinal plants. Value of medicinal plants as a source of foreign exchange for developing countries depends on use of plant as raw materials in pharmaceutical industry. It provides numerous opportunities for developing nations to advance rural well being. Global trade in medicinal plants is of the order of US$ 800 million per year. Export statistics (between 1992 and 1995) indicate that India exported- about 32,600 tonnes of crude drugs, valued at US $46 million (Dhar et al., 2002). China with exports of over 120,000 tons per annum (US$ 264.
5 million) and India with over 32,000 tons per annum dominate the international market. Annum exports of herbal base pharmaceutical companies are showing a constant growth of about 15% or more next only to Information Technology industry (Kumar. 2000).
Turnover of herbal medicines in India as over-the-counter products ethical and classical formulations and home remedies of Ayurveda, Unani, and Siddha systems of medicine is about US$ 1 billion with a meager export of about US $ 80 million (Kamboj, 2000). Worldwide market of herbal medicines is of the order of US$ 60 billion (WHO, 2002) to USS 80 billion (Mathur, 2003) in west. Demand for herbal drugs has reached a new high in recent years. About 1400 herbal preparations are used widely, according to a survey in Member State of European Union (Hoareau and DeSilva, 1999). In 1999, global market for herbal supplements exceeded USS 15 billion with a USS 7 billion market in Europe, USS 2.4 billion in Japan, USS 2.
7 billion in the rest of Asia and USS 3 billion in North America. Use of herbal medicine is widespread. As many as three in ten Americans using botanical remedies in a given year (Raskin etal.
2002). In USA, sales of botanical products (fortified foods, dietary supplementary) increased by more than 40% between 1992 and 1996 to reach a global value of more than USS 14 billion in 1996. Similar trends were observed in Japan and Western European Countries too (Schilter et al„ 2003). Europe imports about 400,000 tonnes of medicinal plants per annum with an average market value of USS 1 billion from Africa and Asia. Germany is by far the largest market and within Europe, largest consumer of medicinal plant spending ? 1.4 billion (USS 2.2 billion) annually.
France is second (?116 million) and the United Kingdom third (? 88 million) (Masood, 1997). Among importers of botanical drugs, Hong Kong is at the top followed by Japan, Germany and USA. These assessments of international trade in medicinal plants include plants and their parts like roots, tubers, wood, extracts, bark, leaves, flowers, fruit, and seeds. Germany and the USA are among the top four countries in import as well as export, expressing their major role as a turntable for medicinal plant raw materials worldwide. Several important modern drugs are extracted directly from plant.
Only 6% of all described species have been analysed chemically and only a small fraction analysed pharmaceutical (Chowdhary, 2002), In USA, the process of synthetic drug discovery and development takes an average of 12 year and any new drug requires investment of an average of USS 230 million. Plant based drugs take a comparatively much less time and expenses than synthetic drugs. Hence, plant based medicines would be cheaper, unless market price are inflated by other considerations (Ramakrishna, 2002). Some drugs are synthesized copies of chemicals found naturally in plant, i.e., aspirin which is a safer synthetic analogue of salicylic acid, an active ingredient of willow bark.
Market share of herbal products made in developing countries remains comparatively low due to lack of research and development and huge investments in making standardized products. Extraction of active principles and manufacture of drug formulations is sophisticated technology- and capital- intensive. A systematic and a concerted approach to this activity have not been maintained for lack of sophisticated equipment and high-cost chemicals. Even in India, there has been a lack of Research and Development on product and process development. Recent research has helped propel the knowledge of other plant, from around the world. This has helped accelerate the development of new supplements and medicines. There is an enormous scope for India to emerge as a major player in global herb based medicines and products by developing its research and development capability.
Research and development capacity:
During the last two decades massive investments has been made on pharmacological, clinical and chemical research all over the world in an effort to discover still more potent plant drugs.
About 250,000 living plant species contain a much greater diversity of bioactive compounds than any chemical library made by humans. But only few plants species have been systematically investigated for presence of bioactive compounds. A few new drug plants have successfully passed the tests of commercial screening. Support for agricultural studies for commercial cultivation is needed to reap the benefits of this labour. In fact, agricultural studies on medicinal plants, by its very nature, demand an equally large investment and higher priority. Research in support of industrial development encompasses all activities ranging from development of superior propagation materials, agro-technology, low cost and efficient processing, technologists to improve quality and yield new formulation to new products and marketing of finished products. There has been capability building in India in recent years in Research and Development sector of medicinal formulation involving plants and its compounds both in private sector as well as government funded research.
There are several private sector and government Research and Development institutions in India. Industry oriented Research and Development insututes are Dabur Research Foundation, Himalaya Health Care, Zpndu Pharmaceuticals, Avestha Gengrtine Technologies, Reliance life Sciences, Hamdard etc. National Botanical Research Institute (NBRI) has been undertaking both basic and applied research in various aspects of plant sciences for conservation and sustainable utilization of plant genetic resources for human welfare and sustainable development. One of the major research and development activities at Central Drugs Research Institute (CDRI) is the exploration of terrestrial plants including Indian traditional medicines for novel molecules for drug development. Indian Agricultural Research Institute, etc., is making major contributions in the field of herbal research. The Government of India has set up several centres through the Indian system of medicine and Homeopathy. National Medicinal Plant Board (NMPB) is one of them, NMPB was set up to coordinate matters relating to medicinal plants including developing policies and strategies for conservation, proper harvesting, cost effective cultivation, research and development, processing and marketing of raw materials to protect, sustain and develop the sector.
Several other agencies both in private sector and or under the government are involved in research and development activities of MAPs along with conservation and upbringing of new plant based products of national and international markets. According to an all India ethnobiological survey, carried out by the Ministry of Environment and Forests, Government of India, over 8000 speices of plants are used by the people of India. Source of 90-95% collection of medicinal plants is forests (wild-collect). Few are cultivated. Biodive’rsity loss, thus, a threat to environment but also a more immediate threat to the livelihood security of rural communities. National studies show 120 medicinal plants are rare or endangered in India.
Open access to medicinal plants in wild is perhaps one of the main reasons for current unsustainable levels of harvesting. Prices paid to gatherers are very low. Commercial plant gatherers often mine natural resources rather than manage them. Factors contributing to unsustainably include lack of sufficient data on wild plant populations, and inadequate regulations and legal protection.
Medical research value:
Experimenting on animals in order to understand the structure and functions of the human’s body began in about 2500 years ago.
Alcmaeonn in Greece cut the optic nerve in living animals and noted that it become blind. Greek and Roman physicians continued such experimentation over next several hundred years. Biomedical research has long relied on plants, animals and microbes to understand normal human physiology and to understand and treat human disease. Research on numerous species has brought medicine into modern era of antibiotics, antidepressants, cancer therapy, organ transplantation, and open heart surgery. Some species are easy to study. Anatomical structures like giant axons of squid or macroscopic eggs of African frog, Xenopus make them especially useful as laboratory subjects. Denning bears or spiny dogfish shark, Squalus acanthias have unique physiological processes that they offer us clues that might not otherwise be discovered to healthy functioning of human body or to treatment of human disease.
Traditional knowledge of treating various kinds of ailments with animals and their products by inhabitants (Bawaria, Mogya, Mccna, etc.) of villages surrounding the Ranthambhore National Park of India is reported. Information of all local animals, parts or products used to cure and methods of preparation were provided. A total of 15 animal’s species were enlisted. They are used as a whole or body parts or by their products like milk, blood, organ for treatment of different 20 kinds of ailments including tuberculosis, asthma, paralysis, constipation, weakness, snake poison etc. Since ancient time’s animals, their parts and their products have constituted part of the inventory of medicinal substances used in various cultures. This is marked by geographical distribution and very deep historical origins.
In Pakistan, 31 animals’ parts and products constitute 9% of all medicinal substances in traditional medicines. Costa-Neto describes the use of 180 animal’s species as in the state of Bahia, Northeastern Brazil. A survey of traditional material of Israel recorded 20 substances of animal origin. Examinations and research show that these substances are similar to those used as remedies throughout human history, irrespective of geographical borders. In India, nearly 15-20 % of the Ayurvedic medicines are based on animals. There are references to nearly 380 types of animal substances in Charaka Samh.
Five products (milk, urine, dung, curd and ghee) of cow are used since ancient times. Besides immense knowledge has come down to modern times, various practices became a part of tradition amongst various groups in India. Animals are used by the Naga tribe of Nagaland. Ao tribe of Nagaland, Iru tribe of Tamilnadu, Chakhcsang tribe of Nagaland, Kachch (Gujarat), Kanik of Tamil Nadu, Bhil, Gamit, Kokna, of Maharashtra, Bhil of Dibrugarh (Assam). This has relevance with the animals that are used by the Mogya, Bawaria, Meena. Residing in these parts of India. Use of urine drop of domestic dogs, Canis familiaris against earache has been reported from tribe of Nagaland. Urine of Capra indices has been also reported to cure asthma, T.
B., paralysis but milk of this animal is used for mouth ulcer. Pavo cristatus legs are used for ear infection, as in Nagaland by Bhil of Rajasthan but legs are boiled with oil in Kachchh for medicinal value. Ao tribe of Nagaland also reportedly uses fat of Sus scrofa in muscular pain.
In Tamil Nadu that is used for Hemorrhoids. Use of antler of Cervus unicolor for eye ailments and fresh blood of Columba livia for paralysis has been also reported in Gujarat. Use of fecal matter of Passer domesticus to treat bady constipation and for treatment of asthma in children in Kachchh. Use of Streptopelia sp. to attain early puberty and dung of Equs hemiomus to cure jaun Joindice reported earlier in India. Ash of Kachuga tentoria carapace is used in asthma, T. B. etc.
but Lissemys punctatus’ carapace is used for healing of cough in Kachchh region. Mostly animal by products are used in traditional system without any loss to animals. Therapeutic information’s is mostly based on animals but some protected species like collared dove (Streptopelia sp.), turtle (Kachuga tentoria), sambhar (Cervus unicolor) are also included as important resources. Kakati and Doulo enlisted six species as rare, among 23 species traditionally used among Chakhesang tribe of Nagaland. Inadequate knowledge about therapeutics, includes children are made to wear beer’s claw around their neck to protect them from evil forces.
There is a need for a transdisciplinary approach on various aspects of zootherapy in such a way that frameworks of methods to amalgamate social components of that practice can be increasingly tested. So, traditional knowledge should be included into strategies of conservation and management of fauna. Further studies are required not only to confirm, the presence of bioactive compound in traditional remedies, but also to emphasize more sustainable use of these resources.