Abstract :
Natural products, including plants, animals and minerals have been the basis of treatment of human diseases. Indigenously, therapeutic compounds were derived from thousands of plants. Ayurveda is a traditional Indian medicinal system being practiced for thousands of years. Considerable research on pharmacognosy, chemistry, pharmacology and clinical therapeutics has been carried out on Ayurveda medicinal plants. Numerous drugs have entered the international market through the study of ethno pharmacology and traditional medicine. Newer guidelines of standardization, manufacture and quality control are required for Ayurveda and other traditional medicines. Employing a unique holistic approach, Ayurveda medicines are usually customized to an individual constitution. Traditional knowledge-driven drug development can follow a reverse pharmacology path and reduce time and cost of development. Powerful new technologies such as automated separation techniques, high-throughput screening (HTS) and combinatorial chemistry are revolutionizing drug discovery. Traditional knowledge will serve as a powerful search engine and most importantly, will greatly facilitate intentional, focused and safe natural products research.
Introduction :
Natural products, including plants, animals and minerals have been the basis of treatment of human diseases. Indigenously, therapeutic compounds were derived from thousands of plants. Ayurveda is a traditional Indian medicinal system being practiced for thousands of years.
Considerable research on pharmacognosy, chemistry, pharmacology and clinical therapeutics has been carried out on Ayurveda medicinal plants. Numerous drugs have entered the international market through the study of ethno pharmacology and traditional medicine. Investigation of leads from the traditional systems of medicine is the current thrust area of R&D.
The foundations of the modern pharmaceutical industry were laid when techniques were developed to produce synthetic replacements for many of the medicines that had been derived from the forest. Morphine from opium and quinine from cinchona are few examples. Tube curare in the West Amazon is from Chondrodendron tomentosum. Curare in modern medicine is made from this and named as tubocurarine. Other pharmaceuticals that have their origin in botanicals include atropine, hyoscine, digoxin, colchicine and emetine. Reserpine, an anti-hypertensive alkaloid (Rauwolfia serpentina) became successful in India.
Many new drugs emerged by using advances in synthetic chemistry, particularly those now being used to treat infections, infestations, cancers, ulcers, heart and blood pressure conditions. Many drugs were developed through random screening of thousands of chemicals. Many others resulted from observations of physicians and scientists. Examples of such drugs include sulphonamides, isoniazid, anti-psychotics, anti-histamines and pencillins. Botanical medications continued to be produced in every country, the clinical efficacy of these was usually not evaluated and the composition of these complex mixtures was only crudely analyzed. Sadly, herbal medicines continued to reflect poor quality control both for materials and clinical efficacy.
Back To Traditional Wisdom :
Lag phase for botanical medicine is now rapidly changing for a number of reasons. Problems with drug-resistant microorganisms, side effects of modern drugs, and emerging diseases where no medicines are available, have stimulated renewed interest in plants as a significant source of new medicines. Pharmaceutical scientists are experiencing difficulty in identifying new lead structures, templates and scaffolds in the finite world of chemical diversity. A number of synthetic drugs have adverse and unacceptable side effects. There have been impressive successes with botanical medicines, most notably quinghaosu, artemisinin from Chinese medicine. Considerable research on pharmacognosy, chemistry, pharmacology and clinical therapeutics has been carried out on ayurvedic medicinal plants.
Numerous molecules have come out of ayurvedic experiential base, examples include rauwolfia alkaloids for hypertension, psoralens in vitiligo, holarrhena alkaloids in amoebiasis, guggulsterons as hypolipidemic agents, mucuna pruriens for Parkinson's disease, piperidines as bioavailability enhancers, baccosides in mental retention, picrosides in hepatic protection, phyllanthins as antivirals, curcumine in inflammation, withanolides, and many other steroidal lactones and glycosides as immunomodulators. A whole range of chronic and difficult-to-treat diseases such as cancers, cardiovascular disease, diabetes, rheumatism and AIDS, all require new effective drugs. Most developing countries have relied and will continue to rely on traditional natural medicines due to the deterrence of high costs of modern allopathic medicines. Natural products research continues to explore a variety of lead structures, which may be used as templates for the development of new drugs by the pharmaceutical industry. In natural products drug discovery, it is important to follow systems-theory and systems-biology applications to facilitate the process.
Ayurveda - The Ancient Science of Life :
Ayurveda remains one of the most ancient and yet living traditions practiced widely in India, Sri Lanka and other countries and has a sound philosophical and experiential basis. Atharvaveda (around 1200 BC), Charak Samhita and Sushrut Samhita26 (1000-500 BC) are the main classics that give detailed descriptions of over 700 herbs. Ayurveda still remains dominant compared to modern medicine, particularly for treatment of a variety of chronic disease conditions. India has about 45,000 plant species and medicinal properties have been assigned to several thousands. About 2000 are found in the literature and indigenous systems commonly employ about 500-700. Some recent work in drug development relates to species of Commiphora (used as a hypolipidaemic agent), Picrorhiza (which is hepato protective), Bacopa (memory enhancer), Curcuma (anti-inflammatory) and Asclepias (cardiotonic).
The ayurvedic database available in classic texts has many applications. It can be used for bio prospecting to identify new sources of medicine and to provide information about likely effects ranging from primary taste to its post-digestive effects. Information about safety, efficacy along with possible indications and contraindications is secured. Valuable information of therapeutic potential and selective benefits to people with different constitutions can be obtained. This will greatly facilitate intentional, focused and safe natural products drug discovery and development.
Herbal Drug Development: Issues and Regulations :
Herbal drug development includes various steps, starting from a passport data on raw materials, correct identification, pharmacognostic and chemical quality standardization, safety and preclinical pharmacology, clinical pharmacology and randomized, controlled clinical trials. Addressing standardization is vital and needs broader consideration. Ayurvedic medicine was developed at times of limited access to technologically variable norms of standardization. The dynamic process of evolution could alter and affect the identity and structure of natural materials. For commercialization, correct identification and supply of raw material to avoid adulteration has become a challenge. Additionally, some botanical species might have been extinct. Lastly, the properties of botanical as recorded in classics may have undergone change due to time and environmental factors. Standardization of Ayurveda botanicals and medicines is required, although one cannot readily apply the typical modern pharmacopoeial standards. The concept of active markers in the process of standardization needs a flexible approach in favor of the complex nature of these materials.
For Ayurveda medicine and other traditional medicines, newer guidelines of standardization are required. Multi-component botanical formulations can be standardized with newer techniques such as DNA fingerprinting, high pressure thin layer chromatography (HPTLC), liquid chromatography-mass spectroscopy. In house monographs need to be evolved and critically followed. For example, a multi-component botanical formulation (Artrex) designed for the treatment of arthritis contains four botanicals and all ingredients, their respective extracts and the formulation are standardized using (high performance liquid chromatography) HPLC and HPTLC (High Performance Thin Layer Chromatography) fingerprint profiles with known markers. This formulation has been granted a US patent.Preclinical studies on Ayurveda medicines are more important for validating drug safety resulting from new procedures, or extractions are used during its preparation. The value of animal testing to establish safety and toxicity is not so critical if the botanicals are used in traditional forms. Suitable animal models help in understanding the mechanism of action or pharmacodynamics of medicines. However, it is well known that no good animal models exist for some human diseases; for example, asthma, diabetes and rheumatism.
Reverse pharmacology helps in reducing three major bottlenecks: costs, time and toxicity.
Combining the strengths of the knowledge base of traditional systems such as Ayurveda with the dramatic power of combinatorial sciences and HTS will help in the generation of structure activity libraries. Ayurveda knowledge and experiential database can provide new functional leads to reduce time, money and toxicity the three main hurdles in drug development. These records are particularly valuable, since effectively these medicines have been tested for thousands of years on people. Thus the Ayurveda knowledge database allows drug researchers to start from a well-tested and safe botanical material.
With Ayurveda, the normal drug discovery course of 'laboratories to clinics' actually becomes from 'clinics to laboratories' a true reverse pharmacology approach. In this process safety remains the most important starting point and efficacy becomes a matter of validation. Globally, there is a positive trend towards holistic health, integrative sciences, systems biology approaches in drug discovery and therapeutics that has remained the unique features of Ayurveda. It will be in the interest of pharmaceutical companies, research rand ultimately the global community to respect the traditions and build on their knowledge and experiential wisdom.
