Chang Yi, Hsia Chih-Wei, Huang Wei-Chieh, Jayakumar Thanasekaran, Hsia Chih-Hsuan, Yen Ting-Lin, Sheu Joen-Rong, Hou Shaw-Min
Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan.
Heliyon. 2023 Sep 21;9(10):e20286. doi: 10.1016/j.heliyon.2023.e20286. eCollection 2023 Oct.
Platelets play a vital role in the formation of dangerous arterial thrombosis. Platelets are activated by adhesive proteins or soluble agonists through their specific receptors. The receptor-mediated signaling pathways lead to common signaling events, which result in shape changes and inside-out signaling, leading fibrinogen binding to glycoprotein IIb/IIIa complex (integrin αβ). This interaction initiates integrin αβ-mediated outside-in signaling, subsequently culminating in granule secretion and aggregation. Myricetin is a flavonoid that occurs in a variety of plants. Although myricetin has been demonstrated to have several bioactive properties, its role in platelet activation has not been extensively studied. The present study demonstrated the ability of myricetin to inhibit platelet aggregation stimulated by collagen, thrombin, and U46619. Myricetin reduced the ATP-release, cytosolic Ca mobilization, and P-selectin expression and the activation of PLCγ2/PKC, PI3K/Akt/GSK3β, and MAPK. Myricetin exerted a direct inhibitory effect on the activation of integrin αβ by disrupting the binding between FITC-PAC-1 and the integrin. Moreover, myricetin suppressed integrin αβ-mediated outside-in signaling, such as integrin β, Src, and Syk phosphorylation on immobilized fibrinogen. In animal studies, myricetin significantly prolonged the occlusion time of thrombotic platelet plug formation in mesenteric microvessels without extending bleeding time. This study concludes that myricetin is a natural integrin αβ inhibitor and a novel antithrombotic agent.
血小板在危险的动脉血栓形成过程中发挥着至关重要的作用。血小板通过其特定受体被黏附蛋白或可溶性激动剂激活。受体介导的信号通路会引发常见的信号事件，导致血小板形状改变和外向内信号转导，使纤维蛋白原与糖蛋白IIb/IIIa复合物（整合素αβ）结合。这种相互作用启动整合素αβ介导的内向外信号转导，随后最终导致颗粒分泌和聚集。杨梅素是一种存在于多种植物中的类黄酮。尽管杨梅素已被证明具有多种生物活性特性，但其在血小板激活中的作用尚未得到广泛研究。本研究证明了杨梅素具有抑制胶原蛋白、凝血酶和U46619刺激的血小板聚集的能力。杨梅素降低了ATP释放、胞质Ca动员、P-选择素表达以及PLCγ2/PKC、PI3K/Akt/GSK3β和MAPK的激活。杨梅素通过破坏FITC-PAC-1与整合素之间的结合，对整合素αβ的激活产生直接抑制作用。此外，杨梅素抑制整合素αβ介导的内向外信号转导，如固定化纤维蛋白原上的整合素β、Src和Syk磷酸化。在动物研究中，杨梅素显著延长了肠系膜微血管中血栓性血小板栓子形成的阻塞时间，而不延长出血时间。本研究得出结论，杨梅素是一种天然的整合素αβ抑制剂和新型抗血栓药物。
