Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets

(+)-Kavain, a 4-methoxy-alpha-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E(2) (PGE(2)) and thromboxane A(2) (TXA(2)), respectively. Exogenously applied AA (100 mu mol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA(2) or 43 pg PGE(2), each parameter being related to 10(6) platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA(2) and PGE(2) with IC50 values of 78, 115, 71, and 86 mu mol/l, respectively. The similarity of the IC50 values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA(2) which induces aggregation of platelets and exocytosis of ATP by its binding on TXA(2)-receptors.