Abstract

Mining of Traditional Medicine for Drug Discovery and Development

Ashwinikumar Raut, Director, Clinical Research & Integrative Medicine, KHS-MRC

Advances in drug sciences and technology continually modify the management practices in modern medicine. There are several stories of blockbuster drugs failing and being recalled. Unlike that, globally, there is an increasing demand for non-variant natural drugs of traditional medicine (TM), used safely, for millennia, by millions of people for their daily healthcare needs. Such popular usage and acceptance of the remedies, from Ayurveda (Ayu) and Traditional Chinese Medicine (TCM), reveal the potential of the untapped ‘subterranean’ resources for natural drug discovery. The history of modern drugs is replete with examples of their origin in TM. But that can be compared to the rare finding of some golden grains after laborious straining of kilos of sand in a riverbed. In contrast, systematic mining, with modern drug research, applied to time-tested/currently used TM remedies would yield unprecedented opportunities to discover and develop new natural drugs. The opportunities and time lost with Cinchona, Rauwolfia serpentina, and Artemisia annua would be avoided by such a shift in paradigm of drug research. The illustrious examples of new drug discoveries, from Ayu and TCM, reinforce this bedside to bench path. India has a unique and distinct categorization for registration of natural products: (1) Ayurvedic/Siddha/Unani (ASU) drugs (under AYUSH), (2) Phytopharmaceuticals (Under the Drugs Controller General) and (3) Ayurceuticals/Food supplements (Under FSSAI). Mining of new products can be for any of these three categories. The paths of Ayurvedic Pharmacoepidemiology (AyPE), Observational studies (OS) and Reverse Pharmacology/Nutraceutics (RP) can be gainfully taken for creating the evidence base of safety and efficacy. However, the dominant paradigm of sequential pre-clinical and clinical Phases used for new chemical entities (NCE) is deeply entrenched. Such NCE mindset thwarts the aforesaid time- and cost-effective path of drug discovery from TM. Ayurvedic pharmacopeia has a rich and diverse reservoir of remedies of herbal, mineral and animal origins. There is an urgent need to scientifically investigate the intricate pharmaceutical processing involved in traditional formulations. Ayurveda-based pharmaceutics is meant to make the remedies safer, more effective, bio-available and bio-compatible. Discovery and development of such Ayurvedic products, with the application of intellectual property criteria (novelty, non-obviousness and utility) can lead to new ASU drugs. For the identified unmet medical needs, remedies can be sourced from the widely used non-Indian medicinal plants, after satisfying the specific rationale of Ayurvedic Dravyaguna (Pharmacology) and reversal of Nidana (patho-physiology). Ginsengs, St John’s wort, Hypericum, Gingko, and Echinicea etc offer such opportunities. These will be new ASU drugs. Novel drug delivery systems can be developed for ASU drugs e. g. nanocurcumin arthro-topical. The new regulations for Phytopharmaceuticals provide immense opportunities for research. We have investigated through OS and RP Arogyavardhini, Yograj Guggulu, Amrutbhallatak, and Panchvalkal- complex formulations. Single Ayurvedic plant-based formulations studied were Atmagupta, Ashoka, Ashwagandha, Haridra, Mamejava, Parijat and Bhallatak. These have given rise to clinical leads for the drug discovery and development for defined clinical conditions. DM-FN 02 is taken for as a Phytopharmaceutical R&D for T2 diabetes. Parijat has antimalarial activity similar to Artemisia in crude form. The Ahara-Aushadha dravyas of Ayurveda offer an immense potential for mining for Nutraceuticals/Ayurceuticals. The diversity of formulations and modes of usage permit one to develop state-of-the art over-the-counter safe and useful products. The examples of Turmeric latte, Amla nutribar, Sunthi chewing gum etc are being explored. In India, there have been some initial hiccups in the domain of nutraceuticals. But there is a great scope to