Gleitz J, Beile A, Wilkens P, Ameri A, Peters T
Universitätsklinik Ulm, Institut für Naturheilkunde, Germany.
Planta Med. 1997 Feb;63(1):27-30. doi: 10.1055/s-2006-957597.
(+)-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 E2 (PGE2) and thromboxane A2 (TXA2), respectively. Exogenously applied AA (100 mumol/l) provoked a 90% aggregation of platelets, the release of 14 pmol ATP, and the formation of either 220 pg TXA2 or 43 pg PGE2, 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 TXA2 and PGE2 with IC50 values of 78, 115, 71, and 86 mumol/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.
（+）-卡瓦因是一种从卡瓦胡椒（胡椒科）中提取的4-甲氧基-α-吡喃酮，对其假定的抗血栓形成作用进行了研究，该作用是根据其抑制花生四烯酸（AA）诱导的血小板聚集、ATP胞吐作用以及抑制环氧合酶（COX）和血栓素合酶（TXS）活性推导而来，后两种作用分别通过前列腺素E2（PGE2）和血栓素A2（TXA2）的生成来评估。外源性应用AA（100 μmol/l）可引起血小板90%的聚集、14 pmol ATP的释放以及220 pg TXA2或43 pg PGE2的形成，每个参数均与10⁶个血小板相关。在AA应用前5分钟给予（+）-卡瓦因，剂量依赖性地减少了聚集、ATP释放以及TXA2和PGE2的合成，IC50值分别为78、115、71和86 μmol/l。IC50值的相似性表明（+）-卡瓦因以抑制COX作为主要靶点，从而抑制TXA2的生成，TXA2通过与TXA2受体结合诱导血小板聚集和ATP胞吐。
