Inhibitory Effects of Panaxatriol from Panax ginseng C. A. Meyer on Phosphoinositide Breakdown Induced by Thrombin in Platelets

Abstract

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and <TEX>$Ca^{2+}$</TEX>-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase <TEX>$C_{\beta}$</TEX> via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate <TEX>$(PIP_2)$</TEX> was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of <TEX>$PIP_2$</TEX>, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free <TEX>$Ca^{2+}([Ca^{2+}])_i$</TEX>) up to 72% as compared with control <TEX>$(30.8{\pm}0.9 nM)$</TEX> in intact platelet. However, PT (100 <TEX>${\mu}g/ml$</TEX>) inhibited the thrombin-elevated <TEX>$[Ca^{2+}]_i$</TEX> to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the <TEX>$[Ca^{2+}]_i$</TEX> level and PIS breakdown.