Plants have formed the basis of sophisticated traditional medicine systems that have been in existence for thousands of years and continue to provide mankind with new remedies. Although some of the therapeutic properties attributed to them have proven to be erroneous, medicinal plant therapy is based on empirical ﬁndings over hundreds and thousands of years. Yet interest in potential chemotherapeutic agents continues. The importance of ethnobotanical inquiry as a cost-effective means of locating new and useful tropical plant compounds cannot be overemphasized.
Approximately half (125,000) of the world’s ﬂowering plant species live in the tropical forests (World Conservation Monitoring Centre, 1992). While Brazil has some 55,000 species of plants, scientific reports exist for only 0.4% of the ﬂora. Tropical rainforests continue to support a vast reservoir of potential drug species. They provide scientists with invaluable compounds to be used as starting points for the development of new drugs. The potential is enormous, as to date only about 1% of tropical species have been studied for their pharmaceutical benefits (Jachak and Saklani, 2007). The existence of undiscovered pharmaceuticals for modern medicine has often been cited as one of the most important reasons for protecting tropical forests, so the high annual extinction rate is a matter for concern, to say the least. To date, about 50 licensed drugs have come from tropical plants (Burslem et al., 2001). Modern medicine usually aims to develop a patentable single compound or a ‘magic bullet’ to treat a speciﬁc condition (Farnsworth et al., 1985).
Many of the plant-derived pharmaceuticals and phytomedicines currently in use today were traditionally used by native people around the world. Some of this knowledge has been documented and codiﬁed or studied scientiﬁcally. Medicinal plants typically contain mixtures of different chemical compounds that may act individually, additively or in synergy to improve health. A single plant may, for example, contain bitter substances that stimulate digestion, anti-inﬂammatory compounds that reduce swellings and pain, phenolic compounds that can act as an antioxidant and venotonics, antibacterial and antifungal tannins that act as natural antibiotics, diuretic substances that enhance the elimination of waste products and toxins and alkaloids that enhance mood and give a sense of well-being.
While European traditions are particularly well known and have had a strong inﬂuence on modern pharmacognosy in the West, almost all societies have well-established customs, some of which have hardly been studied at all. Importantly, the vast majority of people on this planet still rely on their traditional materia medica (medicinal plants and other materials) for their everyday healthcare needs and according to the World Health Organization (WHO, 1999), over 80% of the world’s population (primarily in developing countries) rely on plant-derived medicines for their healthcare.
The study of these traditions not only provides an insight into how the ﬁeld has developed but it is also a fascinating example of our ability to develop a diversity of cultural practices. Traditional medicine often aims to restore balance by using chemically complex plants, or by mixing together several different plants in order to maximize a synergistic effect or to improve the likelihood of an interaction with a relevant molecular target. In most societies today, allopathic and traditional systems of medicine occur side by side in a complimentary way. The former treats serious acute conditions, while the latter is used for chronic illnesses, to reduce symptoms and improve the quality of life in a cost-effective way.
People who use traditional remedies may not understand the scientiﬁc rationale behind their medicines, but they know from personal experience that some medicinal plants can be highly effective if used at therapeutic doses. Since we have a better understanding today of how the body functions, we are in a better position to understand the healing powers of plants and their potential as multi-functional chemical entities for treating complicated health conditions.
Modern allopathic medicine has its roots in ancient medicine, and it is likely that many important new remedies will be discovered and commercialized in the future, as they have been up to now, by following the leads provided by traditional knowledge and experiences. It is estimated that natural products and their derivatives represent more than 50% of all the drugs in clinical use in the world. Medicinal plants contribute no less than 25% of the total (Balandrin et al., 1993). Potent drugs derived from ﬂowering plants include Dioscorea-derived diosgenin, from which all anovulatory contraceptive agents have been derived; pilocarpine to treat glaucoma and dry mouth, derived from a group of South American trees (Pilocarpus spp.) in the Citrus family; two powerful anticancer agents from the Madagascan rosy periwinkle (Catharanthus roseus); laxative agents from Cassia sp. and a cardiotonic agent to treat heart failure from Digitalis species.
Over the past few years, a large number of lead molecules have come out of the traditional ayurvedic system of medicine and include Rauvolfia alkaloids for hypertension, psoralens for vitiligo, Holarrhena alkaloids for amoebiasis, guggulsterones as hypolipidaemic agents, Mucuna pruriens for Parkinson’s disease, piperidines as bioavailability enhancers, bacosides for mental retention, picrosides for hepatic protection, phyllanthins as antivirals, curcumine for inflammation, with anolides and many other steroidal lactones and glycosides as immunomodulators. There is also growing evidence to show that old molecules are finding new applications through a better understanding of traditional knowledge and clinical observations. For example, forskolin or coleol, the labdane diterpene from Coleus forskohlii, has been revisited as adenalyted cyclase activator to treat obesity and atherosclerosis. Similarly, antimicrobial berberine alkaloids are being investigated for potential in treating dyslipidaemia, and involve a mechanism different from statins (Levoye and Jockers, 2008).
Of the drugs approved between 1981 and 2002, 60% of anticancer and 75% of anti-infective drugs could be traced to natural origins (Newman et al., 2003). Although discovered through serendipitous laboratory observation, three of the major sources of anti-cancer drugs on the market or completing clinical trials were derived from North American plants used medicinally by native Americans: the pawpaw (Asimina spp.; the western yew tree (Taxus brevifolia), effective against ovarian cancer; and the mayapple (Podophyllum peltatum), used to combat leukaemia, lymphoma, lung and testicular cancer (Cragg and Newman, 2005).
A multidisciplinary approach combining natural product diversity with combinatorial synthetic and biosynthesis methods may prove particularly effective. Combinatorial chemistry approaches based on natural products from traditional medicine are being used to create screening libraries to identify agents that closely resemble drug-like compounds. Since most of these compounds are part of routinely used traditional medicines, their tolerance and safety are relatively better known than other synthetic chemical entities entering first in-human studies.
The traditional knowledge-inspired pharmacology related to reversing the routine ‘laboratory-to-clinic’ progression of new drugs to a ‘clinic-to-laboratory’ progression. Reverse pharmacology is increasingly being studied and is the rigorous scientific approach of documenting clinical experiences and experiential observations into leads by transdisciplinary exploratory studies for translation into drug candidates or formulations through robust preclinical and clinical research (Takenaka, 2001). In this process, ‘safety’ remains the most important starting point and efficacy becomes a matter of validation. The novelty of this approach is the combination of living traditional knowledge such as that of ayurvedic, African or Amerindian origin and the application of modern technology and processes to provide better and safer leads (Patwardhan and Vaidya, 2010).
A good example that has emanated from ayurvedic medicine is the treatment of psoriasis. Psoriasis is one of the most common dermatological diseases, affecting approximately 2% of the world population with no preventive or curative therapy. Using the reverse pharmacological approach, the botanical drug product Desoris, which is an extract of a single plant that effectively modulates cellular function, has led to an improvement in psoriatic lesions. This product is being developed to conform to US Food and Drug Administration (FDA) guidelines for botanical drug products. It is now undergoing Phase 3 clinical trials in India (Vaidya and Devasagayam, 2007).
Increasingly, it is being proposed that drug discovery need not always be confined to the discovery of a single molecule. Many analysts believe that the current ‘one drug fits all’ approach may be unsustainable in the future. In the management of polygenic syndromes and conditions, there is a renewed interest in multi-ingredient synergistic formulations. Rationally designed polyherbal formulation is being developed as option for multi-target therapeutic and prophylactic applications. This has led to the development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence that can also offer faster and more economical alternatives.
This approach is being used successfully in Tanzania with the Tanga AIDS Working Group (TAWG) and where indigenous knowledge is being used to alleviate suffering from HIV/AIDS (McMillen and Scheinman, 1999). This group has treated over 4000 AIDS patients with herbs prescribed from local healers. This impact has been most significant in reducing opportunistic diseases accompanying HIV infection. These experiences are important in scientific and rational drug discovery process. A crucial challenge is to lever local and global knowledge systems effectively to resolve development challenges (Patwardhan and Mashelkar, 2009).
Finally, drug discovery and development is known to be an extremely complex technology- and capital-intensive process that is facing major challenges with the current target-rich: lead-poor situation. One of the major causes of attrition in drug discovery has been toxicity in human trials and it is also recognized that drugs with novel mechanisms have higher attrition rates. Better validated preclinical targets with proof-of-concept of better efficacy and safety of drugs can mitigate such attrition risks. This is where the reverse pharmacology approach, based on traditional knowledge, can be useful and help reduce failure rates.
Drug discovery strategies based on natural products and traditional medicines are re-emerging as attractive options. It is also being recognized that drug discovery and development need not always be confined to new molecular entities but that rationally designed, carefully standardized, synergistic traditional herbal formulations and botanical drug products with robust scientific evidence can also be alternatives. Herein lie opportunities for the scientific community to add value to indigenous biological resources within an enabling policy framework which promotes and supports innovation.
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