Bioassay-guided isolation of African ethnobotanical anthelmintics

Currently one third of the World's population is infected with soil transmitted helminthes (STH) and schistosomiasis [1]. The burdens of these diseases are serious, including limited physical and mental ability as well as exacerbating malnourishment [2,3]. Since intestinal worms are endemic to Africa, new anthelmintic compounds should be found in the plants used by traditional healers for treating worm infections. The use of C. elegans as a model organism in our bioassay- guided fractionation successfully demonstrates which plant extracts, subsequent fractions, and isolated compounds have significant nematocidal activity [4,5,6,7]. Our research is investigating 21 plant species used for intestinal medicine in Sub-Saharan Africa. Our newly developed anthelmintic bio-assay utilizes tetrazolium salts (MTT) to statistically determine worm mortality, a method superior to current assays based solely on worm movement observations [6]. Extracts from six of the 21 plant species have thus shown significant nematocidal activity. Our chromatographic separations have identified isolates from one extract showing increased activity. LCMS and NMR are currently being used to isolate and characterize the active constituent, suspected to be an ellagic acid derivative [8,9]. Chemical characterization of isolates can be used to improve the safety and efficacy of traditional treatments and will allow for the development of novel anthelmintic drugs to treat infections in humans, livestock and crops.

Acknowledgements: University of the Sciences in Philadelphia, National Cancer Institute, American Society of Pharmacognosy, Ara DerMarderiosian PhD, John Porter PhD, Robert Smith MS, John Beutler PhD, Dave Newman PhD.

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