Poster: Secondary Metabolism

Abs # 299: Mysterious toxicity of kava: Distribution of styrylpyrones and biologically active alkaloids in Piper methysticum (G. Forster), Piperaceae

Presenter:	Dragull, Klaus , dragull@hawaii.edu
Authors	Dragull, Klaus  (A)   Uchida, Janice Y (B)   Nerurkar, Pratibha V (A)   Tang, Chung-Shih  (A)
Affiliations:	(A): Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa (B): Department of Plant and Environmental Protection Sciences, University of Hawaii at Manoa
Web Site:	http://www.ctahr.hawaii.edu

The roots, peeled rootstock, and peeled stems of the South Pacific kava shrub are traditionally pounded in water to give a relaxing drink, which mainly contains suspended styrylpyrones as active constituents. Peelings and leaves are generally avoided. In contrast, herbal supplements used as anxiolytic remedy might have included crude extracts from aerial parts such as the stem peelings (cortex and epidermis tissues), in varying proportions. Recently, rare but severe cases of liver toxicity were associated with the use of kava herbal supplements. We therefore re-investigated the chemistry of different tissues of the kava plant. The known alkaloid, pipermethystine, previously reported from leaves and stems, was found in unexpectedly high concentrations in the leaves and stem peelings tested. Here, the non-alkaloidal styrylpyrones dihydrokavain, dihydromethysticin, and tetrahydroyangonin were also concentrated. In roots, peeled rootstock, and peeled stems, however, the 7,8-dehydrogenated styrylpyrones kavain, methysticin, yangonin and desmethoxyyangonin were more prevalent in relation to the three styrylpyrones mentioned above, but the pipermethystine content was negligible. We have recently isolated and identified two new piperidine alkaloids from certain aerial tissues of the kava plant (Dragull K, Yoshida WY, Tang CS. 2003. Phytochemistry, in press). In our in vitro disc diffusion assays, (S)-pipermethystine inhibited fungal germination and oomycete growth, while the other alkaloids and styrylpyrones did not show any effects. The cellular toxicity of these alkaloids is currently measured in human liver cell lines, in comparison to the styrylpyrones. Cytotoxicity results will be presented at the meeting. (Supported by USDA-CSREES).