Inhibitory mechanisms of dihydroginsenoside Rg3 in platelet aggregation: Critical roles of ERK2 and cAMP

Abstract

Ginsenoside Rg3, a single ginseng saponin, is known to be a major anti-platelet component of protopanaxadiol that is isolated from Korean red ginseng. In this study, we investigated whether dihydroginsenoside Rg3, a stable chemical derivative of ginsenoside Rg3, also demonstrated anti-platelet activity. Dihydroginsenoside Rg3 inhibited thrombin-induced platelet aggregation in a concentration-dependent manner with an IC50 (concentration producing 50% inhibition) of 18.8 +/- 0.4 microM. Ginsenoside Rg3 inhibited platelet aggregation which was induced by thrombin (0.1 U mL(-1)) with an IC50 of 40.2 +/- 0.9 microM. We next determined whether dihydroginsenoside Rg3 affected different types of ligand-induced platelet aggregation. We found that dihydroginsenoside Rg3 inhibited collagen-induced platelet aggregation with an IC50 of 20.0 +/- 0.9 microM. To elucidate the inhibitory mechanism of dihydroginsenoside Rg3 on aggregation, we analysed its downstream signalling pathway. It was interesting to note that dihydroginsenoside Rg3 elevated cyclic AMP production in resting platelets, but did not affect cyclic GMP production. In addition, we found that dihydroginsenoside Rg3 potently suppressed phosphorylation of extracellular signal-regulated kinase 2 (ERK2), which was stimulated by collagen (2.5 microg mL(-1)), but not of p38 mitogen-activated protein kinase. Taken together, our results indicate that dihydroginsenoside Rg3 potently inhibited platelet aggregation via the modulation of downstream signalling components such as cAMP and ERK2.

Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications

“…The role of ginsenoside Rg 3 in the inhibition of platelet aggregation has been described [85]. The role of ginsenosides in protecting human erythrocytes against hemin-induced hemolysis has been described [86].…”

Changes in ginsenoside composition of ginseng berry extracts after a microwave and vinegar process

“…On the other hand, when it comes to ginsenoside Rg3, which displays cancer prevention, cancer cell growth-resistant [10], hypotensive [11], brain cell protection [12], antithrombotic [13] and antioxidant actions [14], MGB-1 peaked with 1.13%, followed by MGB-20 (0.83%) and MGF-B (0.71%). However, no ginsenoside Rg3 was found in ginseng berry extracts.…”

The inhibitory activity of ginsenoside Rp4 in adenosine diphosphate-induced platelet aggregation

“…Ginsenosides are known to exhibit various effects by acting on physical functions such as central nervous, endocrine, immune, and metabolic systems [11], [33], [34], [35]. Among these ginsenosides, Rg1 was reported to be efficacious for antifatigue and memory progression.…”