Drugs from natural products
Thursday, November 30, 2006 08:00 IST
In a paradigm shift from discovery of single bioactive molecules, multiconstituent mainstay of bioactive extracts is emphasized for synergistic and antagonistic studies at cellular and molecular levels at NIPER's R&D center
The Department of Natural Products came into existence as one of the six basic departments opened at the time of inception of NIPER on September 1, 1994. During the laying down of the department apart from high-tech infrastructure, emphasis has also been given to the medicinal plant garden that was created with a view to develop it as a referral center for authentication of botanicals for research purposes.
The department of Natural Products offers two degree programmes, the Masters (M.S Pharm.) and Ph.D. (natural products). The curricula taught here is of interdisciplinary nature with hands on practice with modern instrumentations for isolation, separation and characterization, so as to enable the students to undertake research in drug discovery development and process chemistry of active constituents. The courses are designed in such a manner, so as to integrate traditional knowledge with the modern medicines. The department has established an active enzyme and cell-line based laboratory to undertake drug discovery programs. The department is gearing up to start Master's programme in Traditional Medicines from 2007 academic session, so as to produce human resources for Indian herbal industry.
Grants and fundings
The department has attracted funding by receiving grants from various government (DST, CSIR, ICMR, CCRAS, Ministry of Health, Deptt. of AYUSH, National medicinal plants board etc.), non-government and international agencies. The research has resulted into several publications in journals of both national and international repute, and in generation of intellectual property rights (IPRs).
Natural products R&D
The department focuses on discovering and identifying new chemical entities (NCEs) from natural products of terrestrial, microbial and marine origin for the therapeutic areas like diabetes,inflammation/immunomodulation, gynecology, endocrine dysfunction, cancer, protozoal, infective diseases, obesity and hyperlipidemia etc. The department also has standardized models in the above mentioned areas for the screening of natural products.
In a paradigm shift from discovery of single bioactive molecules, multiconstituent mainstay of bioactive extracts is emphasized for synergistic and antagonistic studies at cellular and molecular levels. During one of such type of a study, effects of extracts of four plants viz. Withania somnifera, Calotropis procera, Trichopus zeylanicus and five species of Ocimum has been done. The Ocimum species studied were found to be the most active ones. In another cell cycle studies, P34cdc2 expression was found to be down regulated by standardized aqueous fraction of W.somnifera that establishes its potential for the development as anti-tumor formulation. The active constituent withanolides were also found to act on the nitric oxide synthase and thereby suppressing the nitrite production. The department has COX-1 and COX-2 catalyzed prostag-landin in-vitro assay screening facility for the discovery of anti-inflamma-tory agents.
The peptides and proteins from natural products based drugs can be potential candidates for treating epidemic viral diseases such as dengue and chickun guinea. No cure has yet been reported for these diseases.
Several Indian medicinal plants like Tridax procumbens, Vitex negundo, Semecarpus anacardium, Cardiospermum halibacum etc. have been evaluated and the active constituents from them have been characterized. This study on inflamation has resulted in the discovery of a new molecule called Indigoferin for the first time. In the field of diabetes two fraction NP-384 and NP-447 have been identified for their anti-diabetic potential after screening of well known medicinal plants like Trigonella foenumgraecum, Momordica charantia, Eugenia jambolana and Gymnema sylves-tre. The area of female disorders have alwaysbeen neglected although, ayurveda describes several plants for their treatment. Keeping this point in mind the department has also worked in this direction. Plants like Asparagus racemosus, A. adscendens, Symplocos racemosa etc. have been evaluated for their effects on LH and FSH hormone levels in immature rats and with success in justifying their use in ayurveda.
Another important facet of the department is the Traditional Medicine development programme with the objective of standardization and quality control of herbal drugs and products. The overall aims of this programme are to meet the demand of cost effective medication and to discover biological agents from sustainable medicinal plant resources. The department is involved in laying down standards, quality control methods, creating databases for authentication of materials of botanical origin, creating libraries of marker / characterizing constituents for identification of raw material/finished products for the government (Deptt. of AYUSH, ICMR etc) and non government agencies.
The department was involved in providing standardized "Pippalyadi Yoga" - a female oral contraceptive formulation for clinical trials at different centers for the CCRAS- AYUSH, Ministry of Health, GOI. The department has also provided technical support to The Ayurvedic Pharmacopoeia of India, Ayurvedic Formulary of India and Indian Pharmacopoeia in the development of standards monographs on botanicals and their formulations. The department has also contributed to the series of books on quality standards of Indian medicinal plants by ICMR.
In addition to isolation and characterization of natural products, semi-synthesis and synthesis of biologically active compounds along with generation of pseudo natural products mainly in area of inflammation, cancer, leishmaniasis, malaria and anti-HIV are other important activities carried out in the department.
Inflammation, metabolic diseases and obesity are the therapeutic areas that are receiving more attention these days for the development of natural products. Inflammation process is considered to be the root cause of almost all the diseases including cancer. Currently the department is involved in discovery of NCEs in the area of inflammation /immunomodulation, wherein the plants used in Indian traditional system of medicine are being explored for activity against pro-inflammatory mediators like TNF-a, IL-1ß, IL-2, IL-6 and nitric oxide (NO). These studies are shedding light on the mechanism of action of the plants for their rational use, thereby increasing their acceptance globally.
The department has established a number of assay protocols for the in-vitro screening of the extracts/compounds. Central animal facility of NIPER is used for the in-vivo studies. Obesity along with metabolic diseases is considered as a lifestyle disease, it is a silent killer which has always been unnoticed. Our traditional system has a mention of many plants that can be used in the treatment of obesity and related disorders. In this direction the department has standardized a pancreatic lipase based screening assay protocol and has undertaken screening of important Indian medicinal plants. This assay is being employed for the identification of NCEs for anti-obesity activity. Other assays for metabolic and related disorders are under development. Recently, the department has taken a research project to explore the medicinal plants wealth and evaluation of traditional medicine practices of North-East India for value addition.
Current incidences that have shaken the Indian health system is the emergence of epidemic viral diseases such as dengue and chickun guinea. No cure has yet been reported for these diseases. This has presented a challenge to the pharmaceutical world for developing new and effective medicines against these diseases. Natural products that have always played a pivotal role in providing the right lead/drug for diseases such as cancer, malaria, can once again lead the way. The peptides and proteins from natural products based drugs can be potential candidates for this area.
The department has initiated a natural products based antiviral drug discovery programme with the main aim for developing agents against HIV infection. This programme can be expanded to discover active molecules for diseases like dengue and chicken guinea in future.
(The author is head, Department of Natural Products,National Institute of Pharmaceutical Education and Research (NIPER), Punjab)