Ginsenoside Rk1 suppresses platelet mediated thrombus formation by downregulation of granule release and αIIbβ3 activation

Abstract Background and objective The ginsenosides from Panax ginseng commonly employed in ethnomedicine in Eastern Asia and its complex physiological studies have shown promising results of some ginsenosides having inhibitory effects on cardiovascular diseases. Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3 and Ro, as previously reported, have inhibitory actions on human platelets. In addition, our recent study has reported the anti-platelet effect of ginsenoside F4 and Rg6, minor fraction of ginseng. However, the inhibitory mechanism of ginsenoside Rk1 (G-Rk1) is still unclear thus, we initiated investigation of the anti-platelet mechanism by G-Rk1 from Panax ginseng. Methodology Our study focused on the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin αIIbβ3 using flow cytometry, intracellular calcium mobilization, fibronectin adhesion, dense granule secretion, and thromboxane B2 secretion. Thrombin-induced clot retraction was also observed in human platelets. Key Results Collagen, thrombin, and U46619-stimulated human platelet aggregation were dose-dependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagen-stimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca2+ release from endoplasmic reticulum, granule release, and αIIbβ3 activity without any cytotoxicity. Conclusions and implications These results indicate that G-Rk1 possess strong anti-platelet effect, proposing a new drug candidate for treatment and prevention of platelet-mediated thrombosis in cardiovascular disease.