Natural Products: Bench to Bedside, An Indian Perspective

Natural products have been and continue to remain a prolific source for the discovery of new drugs and drug leads from ancient times. Recent figures indicate that 80% of drug molecules are natural products and that almost half of the drugs approved since 1994 were based on natural products. The classic examples of drug discovery like morphine, quinine, digoxin, etc. that were obtained from the extracts of their respective plants were mostly responsible for instilling the idea that a single active ingredient must have been responsible for the bioactivity. The drawback of this ideology is that it does not look into the synergy or antagonism characteristics of the mixture. In addition, some constituents may also possess other diverse activities. This idea is proven by several examples reported in the literature where the ascribed pharmacological activity of the extracts could not be matched with that of the isolated pure compounds. Most recent work on medicinal plants involves the rediscovery of effects that have been known for a long period of time at cellular and molecular levels. The uncertainty of earlier studies is obvious in cases of biological activity because of the lack of standardization techniques. Another factor that draws attention is the idea that phytomedicines used in the Western countries are only effective for a particular disease or condition. This is opposite to the Indian system of medicine where formulations are indicated for a myriad of conditions.

The traditional Indian system of medicine has a very long term history of usage for the treatment of a number of diseases and disorders, but lacks recorded safety and efficacy data. However, the main cause for their scientific neglect is due to their multi-constituent nature and the lack of clarity of the mechanism of action. But recently, it has been suggested that drug discovery should not always be limited to discovery of a single molecule and the current 'one disease-one drug' approach may be untenable and that rationally designed polyherbal formulations should also be investigated as an alternative in multi-target therapeutics and prophylaxis. Development of standardized, safe and effective herbal formulations with proven scientific evidence can also provide an economical alternative in several disease areas. The 'kurchi' plant (Holarrhena antidysentrica) has been used for ages in the treatment of dysentery. Conessine, a steroidal alkaloid, isolated from this plant is a well-known example of an anti-amoebic natural product. However, an important point to note is that the active principle, conessine, is toxic, but the herb itself is not. The other example in this category is neoandrographolide from Andrographis paniculata that has been found to be active against bacillary dysentery and like 'kurchi' is used as herbal medicinal formulation. The above mentioned but not exhaustive examples suggest that traditional Ayurvedic plants have a tremendous potential clinically in their parent form but not as individual components. Hence, efforts towards better pharmaceutics should be directed to yield better formulations that can be helpful for a number of conditions. Apart from this, the standardization of the herbal medicinal products also needs improvement and more stringent control for the allopathic medicinal system.

Much needs to be done as far as substantiation of the clinical efficacy and safety are concerned. Most of the companies involved in the manufacture of herbal formulations do not perform clinical trials as there is a proven history for long term safety and efficacy of these formulations. However, the recently imposed ban on Ayurvedic medicines by the European Union is alarming considering the fact that many Indian companies are striving towards modern approaches to quality control and safety parameters. There are numerous possibilities as far as the Ayurvedic and herbal medicines are concerned. The present requirement is to narrow the gap and streamline the information flow between academia, the herbal drugs industry and the clinical research organizations to develop better herbal formulations for therapeutic usage.

NIPER is actively involved in the discovery of NCEs from plants as well as by semi-synthetic modification of these NPs to give more potent compounds, particularly in the areas of inflammation (NFκB and cytokines), metabolic disorders like obesity, HIV, hormonal disorders, etc. There has been a limited success in these areas, but the future is definitely promising. In addition, NIPER is involved in the standardization of herbal and Ayurvedic medicines by developing HPLC, HPTLC and LCMS profiles of various formulations as well as being instrumental in developing various monographs for the standardization of Ayurvedic medicines. We have also standardized an Ayurvedic formulation called 'Pippalyadi Yoga', a herbal contraceptive and have performed clinical trials using this formulation.