In Vitro Toxicity of Kava Alkaloid, Pipermethystine,
in HepG2 Cells as Compared to Kavalactones

Nerurkar PV, Dragull K, Tang CS.
Department of Molecular Biosciences and Bioengineering,
College of Tropical Agriculture and Human Resources,
University of Hawaii at Manoa, Honolulu, HI 96822.
Toxicol Sci. 2004 Jan 21


BKava herbal supplements have been recently associated with acute hepatotoxicity, leading to the ban of kava products in approximately a dozen countries around the world. It is suspected that some alkaloids from aerial kava may have contributed to the problem. Traditionally, Pacific Islanders employ primarily the underground parts of the shrub to prepare the kava beverage. However, some kava herbal supplements may contain ingredients from aerial stem peelings. The aim of this project was to test the in vitro effects of a major kava alkaloid, pipermethystine (PM) found mostly in leaves and stem peelings and kavalactones such as 7,8-dihydromethysticin (DHM), desmethoxyyangonin (DMY) that are abundant in the roots. Exposure of human hepatoma cells, HepG2, to 100 micro M of PM caused 90% loss in cell viability within 24 h, while 50 micro M caused 65% cell death. Similar concentrations of kavalactones did not affect cell viability up to 8 days of treatment. Mechanistic studies indicate that in contrast to kavalactones, PM significantly decreased cellular ATP levels, mitochondrial membrane potential and induced apoptosis as measured by the release of caspase-3 after 24 h of treatment. These observations suggest that PM, rather than kavalactones, is capable of causing cell death, probably in part by disrupting mitochondrial function. Thus, PM may contribute to rare but severe hepatotoxic reactions to kava. 1490.
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