Inhibitory Effect of 20(S)-Ginsenoside Rg3 on Human Platelet Aggregation and Intracellular Ca(2+) Levels via Cyclic Adenosine Monophosphate Dependent Manner

Intracellular Ca(2+) ([Ca(2+)](i)) induces platelet aggregation, and influences the activation of aggregation associated-molecules. The increased [Ca(2+)](i) activates both the Ca(2+)/calmodulin-dependent phosphorylation of the myosin light chain and the diacylglycerol-dependent phosphorylation of pleckstrin to trigger granule secretion (i.e., dense body and α-granule) and platelet aggregation. This study was carried out to elucidate the antagonistic effect of 20(S)-ginsenoside Rg3 (G-Rg3) present in Panax ginseng Mayer on Ca(2+). G-Rg3 inhibited thrombin-induced human platelet aggregation in a dose-dependent manner and suppressed thrombin-induced elevation of [Ca(2+)](i) mobilization. G-Rg3 increased the levels of cAMP, and subsequently, elevated the phosphorylation of inositol 1,4,5-triphosphate receptor I (Ser(1756)) during thrombin-induced human platelet aggregation. Moreover, G-Rg3 inhibited thapsigargin-induced Ca(2+) influx and the thrombin-induced elevation of extracellular signal-regulated kinase 2 phosphorylation. G-Rg3 exhibited an inhibitory effect on [Ca(2+)](i) levels leading to granule release and thus a therapeutic potential against platelet-mediated thrombotic disease is suggested.