Inhibition of Platelet MAO-B by Kava Pyrone-Enriched Extract from Piper Methysticum Forster (Kava-Kava)

Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC₅₀ 24 μM) and disrupted platelet homogenates (IC₅₀ 1.2 μM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (±)-methysticin > yangonin > (±)-dihydromethysticin > (+)- dihydrokavain > (±)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (±)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 μM and 1.14 ?M respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.