Antithrombotic Action of the Kava Pyrone (+)-Kavain Prepared from Piper methysticum on Human Platelets*

Abstract

(+)-Kavain, a 4-methoxy-α-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 E₂ (PGE₂) and thromboxane A₂ (TXA₂), respectively. Exogenously applied AA (100 µmol/l) provoked a 90% aggregation of platelets, the release of 14pmol ATP, and the formation of either 220 pg TXA₂ or 43 pg PGE₂, each parameter being related to 10⁶ platelets. An application of (+)-kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA₂ and PGE₂ with IC₅₀ values of 78, 115, 71, and 86 µmol/l, respectively. The similarity of the IC₅₀ values suggest an inhibition of COX by (+)-kavain as primary target, thus suppressing the generation of TXA₂ which induces aggregation of platelets and exocytosis of ATP by its binding on TXA₂-receptors.

Key words

Cyclooxygenase - kavain - kava pyrones - Piper methysticum - Piperaceae - platelets