Antiplatelet activity of a Korean red ginseng–derived saponin fraction and its inhibition of influenza A virus–induced thrombosis

Abstract

Background: Platelets play a central role in thrombus formation, which is a major cause of morbidity and mortality worldwide. Viral infections have been reported to further promote thrombus formation, posing a critical risk in unpredictable pandemic situations. Therefore, we evaluated whether a Korean red ginseng–derived saponin fraction could serve as a safe and effective antithrombotic agent by assessing its inhibitory effects. Methods: Human platelets were examined using an aggregometer, flow cytometry, fluorescence assays, ELISA kits, and western blotting to assess cGMP, intracellular Ca2+ levels, fibrinogen binding, granule secretion (ATP and serotonin), and phosphorylation of IP3R, VASP, MAPKs, PI3K/Akt, and cPLA2. Thrombin-induced clot retraction was quantified. The in vivo effects were further evaluated in influenza A virus (IAV)-infected mice using a FeCl3-induced carotid artery thrombosis model, where thrombus formation and blood flow were monitored. Results: The saponin fraction markedly inhibited platelet aggregation, enhanced cGMP production, and increased phosphorylation of IP3R and VASP Ser239. Conversely, it suppressed phosphorylation of MAPKs (JNK and p38), PI3K/Akt, and cPLA2, thereby blocking downstream signaling pathways. In vivo, IAV infection accelerated thrombus formation and reduced blood flow, whereas administration of the saponin fraction significantly attenuated these pathological changes. Conclusion: The saponin fraction effectively suppressed platelet activation in vitro and thrombus formation in vivo, even under virus-induced prothrombotic conditions. These findings suggest that the saponin fraction has potential as a safe and effective natural antithrombotic agent.