Evaluating kava extracts and kavalactones for mutagenicity and toxicity

Abstract

Kava (Piper methysticum) has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. The active components of kava rootstock are contained primarily in the lipid‐soluble resin. The compounds of greatest pharmacological interest are the styryl α‐pyrones or kavalactones and represent 3–20% of the dried rhizome. At least 16 lactones have been isolated from kava and six compounds, namely, kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the major kavalactones, and account for approximately 96% of the lipid resin. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver injury in humans, including several who required liver transplants after using kava supplements. In order to study the cellular toxicity and mutagenicity, two commercial samples of kava and the eight pure kavalactones, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation, but there were significant differences in toxicity among the kavalactones.