TY - JOUR
T1 - Ginsenoside Rg5 inhibits platelet aggregation by regulating GPVI signaling pathways and ferric chloride-induced thrombosis
AU - Akram, Abdul Wahab
AU - Shin, Jung Hae
AU - Batmunkh, Uyanga
AU - Saba, Evelyn
AU - Kang, Yong Myung
AU - Jung, Sunjun
AU - Han, Jee Eun
AU - Kim, Sung Dae
AU - Kwak, Dongmi
AU - Kwon, Hyuk woo
AU - Rhee, Man Hee
N1 - Publisher Copyright:
© 2025
PY - 2025/7
Y1 - 2025/7
N2 - Background: Platelet hyperactivation is a major factor in thrombotic complications such as myocardial infarction and ischemic stroke. Ginsenoside Rg5 is a minor ginsenoside, and among its various beneficial pharmacological effects, its antithrombotic potential has not been extensively studied. Methods: Human platelets were isolated and treated with Rg5 (35-100 μM) before stimulation with agonists such as collagen, thrombin, and U46619. Platelet aggregation, granule secretion, calcium mobilization, thromboxane A2 production, fibrinogen binding, and clot retraction were evaluated. The effects of Rg5 on signaling pathways were determined via Western blot analysis of key proteins. In vivo, the antithrombotic efficacy was assessed using ferric chloride (FeCl3)-induced thrombosis in mice. Results: Rg5 dose-dependently inhibited collagen-induced platelet aggregation (IC50 = 42.5 μM) and selectively inhibited GPVI-mediated signaling compared to thrombin and U46619. Rg5 suppressed intracellular calcium mobilization, granule secretion, and thromboxane A2 production, with no cytotoxicity observed. Rg5 downregulated key signaling proteins (p-PI3K, p-AKT, p-cPLA2, and p-p38) while upregulating p-VASP (S157 and S239), suggesting its role in elevating cyclic nucleotide signaling. Additionally, Rg5 inhibited CD162 expression that was induced in the presence of collagen and oxidized low-density lipoprotein. It also prevented fibrinogen and fibronectin binding and significantly reduced clot retraction. In vivo, Rg5 (20 mg/kg) significantly prolonged the carotid artery occlusion time and prevented thrombus formation, outperforming aspirin (100 mg/kg). Conclusion: Ginsenoside Rg5 exhibits potent antiplatelet activity by selectively targeting GPVI-mediated platelet activation and modulating key intracellular signaling pathways. These results suggest that Rg5 could be utilized to develop safer and natural antiplatelet therapies.
AB - Background: Platelet hyperactivation is a major factor in thrombotic complications such as myocardial infarction and ischemic stroke. Ginsenoside Rg5 is a minor ginsenoside, and among its various beneficial pharmacological effects, its antithrombotic potential has not been extensively studied. Methods: Human platelets were isolated and treated with Rg5 (35-100 μM) before stimulation with agonists such as collagen, thrombin, and U46619. Platelet aggregation, granule secretion, calcium mobilization, thromboxane A2 production, fibrinogen binding, and clot retraction were evaluated. The effects of Rg5 on signaling pathways were determined via Western blot analysis of key proteins. In vivo, the antithrombotic efficacy was assessed using ferric chloride (FeCl3)-induced thrombosis in mice. Results: Rg5 dose-dependently inhibited collagen-induced platelet aggregation (IC50 = 42.5 μM) and selectively inhibited GPVI-mediated signaling compared to thrombin and U46619. Rg5 suppressed intracellular calcium mobilization, granule secretion, and thromboxane A2 production, with no cytotoxicity observed. Rg5 downregulated key signaling proteins (p-PI3K, p-AKT, p-cPLA2, and p-p38) while upregulating p-VASP (S157 and S239), suggesting its role in elevating cyclic nucleotide signaling. Additionally, Rg5 inhibited CD162 expression that was induced in the presence of collagen and oxidized low-density lipoprotein. It also prevented fibrinogen and fibronectin binding and significantly reduced clot retraction. In vivo, Rg5 (20 mg/kg) significantly prolonged the carotid artery occlusion time and prevented thrombus formation, outperforming aspirin (100 mg/kg). Conclusion: Ginsenoside Rg5 exhibits potent antiplatelet activity by selectively targeting GPVI-mediated platelet activation and modulating key intracellular signaling pathways. These results suggest that Rg5 could be utilized to develop safer and natural antiplatelet therapies.
KW - Anti-platelet effects
KW - Cardioprotective effects
KW - FeCl-Induced thrombosis
KW - GPVI signaling
KW - Ginsenoside Rg5
UR - https://www.scopus.com/pages/publications/105002752739
U2 - 10.1016/j.jgr.2025.04.002
DO - 10.1016/j.jgr.2025.04.002
M3 - Article
AN - SCOPUS:105002752739
SN - 1226-8453
VL - 49
SP - 460
EP - 469
JO - Journal of Ginseng Research
JF - Journal of Ginseng Research
IS - 4
ER -