Anti-platelet Activity of Erythro-(7S,8R)-7-acetoxy-3,4,3′, 5′-tetramethoxy-8-O-4′-neolignan from Myristica fragrans

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. In this study, we investigated the anti-platelet activity of erythro-(7S,8R)-7-acetoxy-3,4,3,5-tetramethoxy-8-O-4-neolignan (EATN), a neolignan isolated from Myristica fragrans, using human platelets. EATN preferentially inhibited thrombin- and platelet-activating factor (PAF)-induced platelet aggregation without affecting platelet damage in a concentration-dependent manner with IC50 values of 3.2 +/- 0.4 and 3.4 +/- 0.3M, respectively. However, much higher concentrations of EATN were required to inhibit platelet aggregation induced by arachidonic acid. EATN also inhibited thrombin-induced serotonin and ATP release, and thromboxane B-2 formation in human platelets. Moreover, EATN caused an increase in cyclic AMP (cAMP) levels and attenuated intracellular Ca2+ mobilization in thrombin-activated human platelets. Therefore, we conclude that the inhibitory mechanism of EATN on platelet aggregation may increase cAMP levels and subsequently inhibit intracellular Ca2+ mobilization by interfering with a common signaling pathway rather than by directly inhibiting the binding of thrombin or PAF to their receptors. This is the first report of the anti-platelet activity of EATN isolated from M. fragrans. Copyright (c) 2013 John Wiley & Sons, Ltd.