Microbial metabolism of kava lactones from Piper methysticum

Piper methysticum Forst (Kava Kava) is a perennial herb of the family Piperaceae grown widely in the Pacific Islands. The South Pacific islanders have been using a beverage traditionally prepared from kava roots for thousands of years in social, recreational and ceremonial events, and also as a remedy for stress and anxiety. It has been used in traditional herbal medicine for treating gonorrhea, menstrual pain, tuberculosis, and respiratory tract infections. Phytochemical constituents in P. methysticum have been extensively studied, and its major ingredients are known as kava lactones, the lipophilic natural products in roots.

These lipophilic kava lactones show extremely low solubility in water, which would be expected to reduce their absorption rates and appears to be responsible for the variable and low extent of metabolism observed. Previous in vitro and in vivo metabolism studies using rat and human liver microsomes as well as microorganisms have resulted in the isolation of various kava lactone derivatives produced via reduction, demethylation and hydroxylation.

In our research program on microbial metabolism of kava lactones from P. methysticum, several microorganisms were found to be capable of metabolizing kava lactones. Scale-up fermentation studies of kava lactones using these microorganisms have resulted in the production of several metabolites with increased polarity. The structures of these metabolites were determined using various spectroscopic techniques.