Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China.
Department of Cardiology, Lishui Central Hospital, Lishui, China.
Thromb Res. 2014 Jan;133(1):57-65. doi: 10.1016/j.thromres.2013.10.032. Epub 2013 Oct 25.
Derived from the root of Panax ginseng C.A.Mey, Panax notoginsenosides (PNS) is a widely used herbal medicine to treat atherothrombotic diseases in Asian medicine. Ginsenoside Rg1 is one of the main compounds responsible for the pharmaceutical actions of PNS. As platelets play pivotal roles in atherothrombogenesis, we therefore studied the effect of Rg1 on platelet activation and its underlying mechanisms.
Human platelets are obtained from healthy subjects. Platelet activation and the inhibition of Rg1 were assessed by Born aggregometer, flow cytmetry, flow chamber and western blot. The in vivo thrombosis model was induced by 10% FeCl3 on mesenteric arterioles of wild type B57/b6 mice.
Rg1 significantly inhibited platelet aggregation induced by thrombin, ADP, collagen and U46619, e.g., aggregation rate stimulated by 0.1UmL(-1) thrombin was decreased 46% by Rg1. Rg1 also reduced thrombin (0.1UmL(-1))-enhanced fibrinogen binding and P-selectin expression of single platelet by 81% and 66%, respectively. Rg1 affected αIIbβ3-mediated outside-in signaling as demonstrated by diminished platelet spreading on immobilized fibrinogen. Rg1 also decreased the rate of clot retraction in platelet rich plasma. Furthermore, Rg1 decreased platelet adhesion on collagen surface under a shear rate correlated to the arterial flow (1000s(-1)) by approximately 70%. Western blot showed that Rg1 potently inhibited ERK phosphrylation. The in vitro findings were further evaluated in the mouse model of in vivo arterial thrombosis, and Rg1 was found to prolong the mesenteric arterial occlusion time (34.9±4.1min without and 64.3±4.9min with Rg1; p<0.01).
Rg1 inhibits platelet activation via the inhibition of ERK pathway, and attenuates arterial thrombus formation in vivo.
源于人参 Panax ginseng C.A.Mey 的根，人参皂苷（PNS）是一种广泛用于治疗亚洲医学中的动脉血栓疾病的草药。人参皂苷 Rg1 是 PNS 产生药物作用的主要化合物之一。由于血小板在动脉血栓形成中起着关键作用，因此我们研究了 Rg1 对血小板激活及其潜在机制的影响。
从健康受试者中获得人血小板。通过 Born 聚集仪、流式细胞术、流动室和 Western blot 评估血小板激活和 Rg1 的抑制作用。在野生型 B57/b6 小鼠的肠系膜小动脉上用 10% FeCl3 诱导体内血栓形成模型。
Rg1 显著抑制由凝血酶、ADP、胶原和 U46619 诱导的血小板聚集，例如，由 0.1UmL(-1) 凝血酶刺激的聚集率通过 Rg1 降低了 46%。Rg1 还分别减少了凝血酶（0.1UmL(-1)）增强的纤维蛋白原结合和血小板 P-选择素表达的 81%和 66%。Rg1 影响αIIbβ3 介导的外向信号转导，如在固定化纤维蛋白原上血小板扩散减少所示。Rg1 还降低了富含血小板的血浆中的凝块回缩率。此外，在与动脉血流（1000s(-1)）相关的剪切率下，Rg1 使血小板在胶原表面的粘附率降低约 70%。Western blot 显示 Rg1 强烈抑制 ERK 磷酸化。在体内动脉血栓形成的小鼠模型中进一步评估了体外发现，并且发现 Rg1 延长肠系膜动脉闭塞时间（无 Rg1 为 34.9±4.1min，有 Rg1 为 64.3±4.9min；p<0.01）。
Rg1 通过抑制 ERK 途径抑制血小板激活，并减轻体内动脉血栓形成。
