PDF(Pubmed)
Abstract：
Platelets assume a pivotal role in the cardiovascular diseases (CVDs). Thus, targeting platelet activation is imperative for mitigating CVDs. Ginkgetin (GK), from Ginkgo biloba L, renowned for its anticancer and neuroprotective properties, remains unexplored concerning its impact on platelet activation, particularly in humans. In this investigation, we delved into the intricate mechanisms through which GK influences human platelets. At low concentrations (0.5-1 μM), GK exhibited robust inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Intriguingly, thrombin and U46619 remained impervious to GK\'s influence. GK\'s modulatory effect extended to ATP release, P-selectin expression, intracellular calcium ([Ca2+ ]i) levels and thromboxane A2 formation. It significantly curtailed the activation of various signaling cascades, encompassing phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3β and mitogen-activated protein kinases. GK\'s antiplatelet effect was not reversed by SQ22536 (an adenylate cyclase inhibitor) or ODQ (a guanylate cyclase inhibitor), and GK had no effect on the phosphorylation of vasodilator-stimulated phosphoproteinSer157 or Ser239 . Moreover, neither cyclic AMP nor cyclic GMP levels were significantly increased after GK treatment. In mouse studies, GK notably extended occlusion time in mesenteric vessels, while sparing bleeding time. In conclusion, GK\'s profound impact on platelet activation, achieved through inhibiting PLCγ2-PKC cascade, culminates in the suppression of downstream signaling and, ultimately, the inhibition of platelet aggregation. These findings underscore the promising therapeutic potential of GK in the CVDs.
摘要：
血小板在心血管疾病（CVDs）中起着举足轻重的作用。因此，靶向血小板活化对于减轻CVD至关重要.银杏素(GK),来自银杏L,以其抗癌和神经保护特性而闻名，关于其对血小板活化的影响仍有待探索，特别是在人类中。在这次调查中,我们深入研究了GK影响人类血小板的复杂机制。在低浓度（0.5-1μM），GK对胶原蛋白和花生四烯酸（AA）诱导的血小板聚集具有强大的抑制作用。有趣的是，凝血酶和U46619仍然不受GK的影响。GK的调节作用扩展到ATP释放，P-选择素表达,细胞内钙（[Ca2]i）水平和血栓烷A2的形成。它大大减少了各种信号级联的激活，包括磷脂酶Cγ2（PLCγ2）/蛋白激酶C（PKC），磷酸肌醇3-激酶/Akt/糖原合酶激酶-3β和丝裂原活化蛋白激酶。SQ22536（腺苷酸环化酶抑制剂）或ODQ（鸟苷酸环化酶抑制剂）不能逆转GK的抗血小板作用，和GK对血管扩张剂刺激的磷蛋白Ser157或Ser239的磷酸化没有影响。此外，GK治疗后，环AMP和环GMP水平均未显着增加。在老鼠研究中，GK显著延长肠系膜血管闭塞时间，同时节省出血时间。总之,GK对血小板活化的深远影响，通过抑制PLCγ2-PKC级联来实现，以抑制下游信号和，最终,抑制血小板聚集。这些发现强调了GK在CVD中的有希望的治疗潜力。
