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

Background and objective: Synthetic ginsenoside compounds G-Rp (1,3, and 4) and natural ginsenosides in Panax ginseng 20(S)-Rg3, Rg6, F4 and Ro have inhibitory actions on human platelets. 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 to investigate the action of G-Rk1 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin alpha(IIb)beta(3) 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 dosedependently inhibited by G-Rk1, while it demonstrated a more effective suppression on collagenstimulated platelet aggregation using human platelets. Moreover, G-Rk1 suppressed collagen-induced elevation of Ca2+ release from endoplasmic reticulum, granule release, and alpha(IIb)beta(3) 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. (C) 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

Automated summary

The study showed that G-Rk1 has an inhibitory effect on human platelet aggregation, particularly more effective on collagen-stimulated platelet aggregation. It can also suppress the activity of various platelet signaling molecules, thus blocking platelet formation of thrombosis.