Lanka's rich bio diversity an economic asset

by Gamini Warushamana

Sri Lanka has a very rich bio diversity, which we can exploit for the economic development of the country. Therefore, Natural Products Chemistry (NPC) is one important research area that Sri Lanka should develop and exploit, said Prof. Leslie Gunatilaka, who was the guest of honour and keynote speaker at Chemtech 2007, an international conference held recently at the BMICH.

Prof. Gunatilaka is the director of the Southwest Centre for Natural Products Research and Commercialisation, College of Agriculture and Life Sciences at the University of Arizona, USA.

Here are excerpts of his interview with the Sunday Observer.

Natural products constitute small molecules produced by plants, micro organisms, marine invertebrates and insects. In Sri Lanka there are over 3,500 flowering plant species and of these about 850 are endemic, that is they are found only in Sri Lanka. Of the 3,500 total plant species, about 750 are used in our indigenous systems of medicine on which about 75% of our population depends for their primary health care.

The bio diversity and especially the plants used in our indigenous systems of medicine are valuable economic assets for Sri Lanka, because natural or plant medicines are becoming increasingly popular all over the world.

People today realise the value of natural medicines since they are less toxic compared to synthetic medicines. In the US and Europe herbal medicine is becoming very popular.

In the United States the annual market for herbal supplements is over $ 40 billion. This is a huge market to tap if Sri Lanka can properly use its rich bio diversity and medicinal plant resources.

Natural products research

Over the past few decades natural products research has undergone a number of significant changes and a variety of natural products have been isolated, characterised, and synthesised, providing treatment for many incurable human and animal diseases and affording agrochemicals for improved food production. Many natural products have evolved to enhance the survival of the producing organism and therefore should have some biological and or ecological relevance.

A survey carried out in the US suggests that over 60% of anti-cancer and anti-infective drugs approved for clinical use are of natural origin or based on natural product models.

In addition, the healing properties of medicinal plants employed in traditional medicines have been associated with medicinally (pharmacologically) active natural products in these plants, sometimes acting synergistically and or antagonistically in enhancing their biological activity and or reducing their toxicity. There are some medicines that are becoming very popular in the US and most of them are imported to the country.

If we can grow and harvest these plants systematically and process them in accordance with the required standards of the international market it would be a very profitable business for an agriculturally based economy such as Sri Lanka. Withania somnifera, the medicinal plant we know as Amukkara, is one such example.

The use of this plant dates back to over 3,000 years in the Indian Ayurvedic medical tradition, where preparations of dried root powder are called Ashwagandha.

This plant grows readily in semi-dry and dry habitats throughout the world. The primary bio active components of Ashwagandha include a class of steroidal lactones called withanolides.

Interestingly, plants that contain withanolides have extensive use in traditional medicines as general tonics to increase energy, reduce stress, improve overall health and longevity and prevent diseases of the elderly.

Anti cancer activity

Ashwagandha is currently regulated in the US and Europe as a dietary supplement with recommended indications for arthritis, anxiety, insomnia and stress. The anti-cancer activity of the major constituent of Ashwagandha, the withanolide withaferin A, has been studied for nearly forty years, but its mode of action and its protein target has remained elusive.

If withaferin A is to become a usable drug in modern medicine, two additional questions - ease of its production and conversion of it into a water soluble analogue - have to be addressed.

Research carried out by Prof. Gunatilaka and his team at the University of Arizona have focused on these aspects. In our studies to elucidate the mode of action of withaferin A and to identify its protein target, we have recently shown that withaferin A bestows an aberrant gain of function on to the protein, Annexin II, resulting in hyper-bundling of F-actin that leads to its anti-cancer activity.

Our results indicate that withaferin A can modulate many of the functions and cellular processes usually attributed to Annexin II, including actin microfilament bundling and that modulation of Annexin II function by withaferin A can have detrimental effects on cancer cell migration, viability and growth.

It is known that the majority of cancer fatalities are primarily due to cancer cell migration causing cancers to spread (metastasize) into vital organs and therefore compounds disrupting cancer cell migration are promising anti-cancer drugs. The results of our studies were recently published in Nature Chemical Biology.

Withaferin A, the major constituent of Withania somnifera responsible for its anti-cancer and other biological activities is found in both aerial parts and roots of the plant. It is commercially available at a cost of $195 (about Rs. 21,700) for 10 milligrams.

The seasonal and slow-growing nature of the plant makes it a commercially non-viable source of this compound.

In a study to explore the efficient methods of production of withaferin A, Prof. Gunatilaka and his team have developed a soil-less aeroponic plant culture technique which has resulted in a shorter time-course, possibility of continuous harvest of bio-mass, and several-fold increase in the yield of withaferin A.

Extraction methodology

By manipulation of the extraction methodology they have also isolated a novel water-soluble analogue of withaferin A with a biological activity profile that is similar to the parent compound.

Prof. Gunatilaka said that natural products chemistry (NPC) is one area in which research in Sri Lanka is highly developed. The Universities of Colombo, Kelaniya, Peradeniya, Sri Jayawardenapura, and the Open University, all have very capable scientists trained in natural products chemistry.

Research institutes such as the Institute of Fundamental Studies and Industrial Technology Institute are also working in this field.

It is a good idea to bring all scientists interested in the NPC together, define priorities for the country and provide them with the required facilities and research funds.

Genomic revolution has influenced many areas of chemistry including natural products chemistry. Unlike in the past, chemists have begun to interact with biologists and geneticists in their pursuit of exploring benefits of natural products chemistry to mankind. In Sri Lanka this type of interdisciplinary interaction in natural products research is yet to be developed.

Potential high returns

Sri Lanka has to invest in research with potential high returns. Once we thought that astronomy was one such area of research.

Now nano- technology is considered as an area that we have an advantage over other fields. For a developing country such as Sri Lanka with an agriculturally based economy, The NPC has more potential, because of the rich bio-diversity, medicinal plant and human resources as well as the present level of research in the country comparable with international standards.

Prof. Gunatilaka and others in the early 1970s identified this advantage Sri Lanka has in the area of natural products chemistry. He did his Ph.D. research at the Imperial College of Science and Technology, University of London, in synthetic organic chemistry under the guidance of the Nobel laureate, the late Prof. Sir Derek H. R. Barton, on a Commonwealth scholarship.

However, on returning to Sri Lanka after his postgraduate studies he realised the difficulty of carrying out research in synthetic chemistry due to the lack of requisite research facilities and chemicals.

This made him to join the research group at Peradeniya University led at that time by the late Prof. M. U. S. Sultanbawa to conduct research in NPC.

He has been very productive and over half of his 200 research publications and book chapters have resulted from the work carried out in Sri Lanka and during his tenure as the head of Department of Chemistry in 1987, the Peradeniya NPC group was awarded the prestigious Presidential Gold Medal for creating a centre of excellence in natural products research at the University of Peradeniya.

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