Antiplatelet activity of chrysin via inhibiting platelet αIIbβ3‐mediated signaling pathway

作者：Gang Liu, Wenlian Xie, Aodi He, Xingwen Da, Minglu Liang, Guang-Qiang Yao, Ji‐Zhou Xiang, Cunji Gao, Zhangyin Ming · 发表于：Molecular Nutrition & Food Research · 年份：2016 · DOI：10.1002/mnfr.201500801 · 被引用次数：44 · 研究领域：Flavonoids in Medical Research、Flavonoids in Medical Research、Platelet Disorders and Treatments

SCOPE: Propolis is thought to help prevent thrombotic and related cardiovascular diseases in humans. Chrysin, a bioflavonoids compound found in high levels in propolis and in honey, has been reported to possess antiplatelet activity. However, the mechanism by which it inhibits platelet function is unclear. METHODS AND RESULTS: The effects of chrysin on agonist-activated platelet-aggregation, granule-secretion, and integrin αIIbβ3 activation were examined. Its effects on the phosphorylation of Akt, GSK3β, MAPKs, and several proteins of the glycoprotein VI (GPVI) signaling pathway were also studied on collaged-activated platelets. In addition, human platelet spreading on immobilized fibrinogen was also tested. We found that chrysin dose dependently inhibited platelet aggregation and granule secretion induced by collagen, as well as platelet aggregation induced by ADP, thrombin, and U46619. Chrysin also markedly reduced the number of adherent platelets and the single platelet spreading area on immobilized fibrinogen. Biochemical analysis revealed that chrysin inhibited collagen-induced activation of Syk, PLCγ2, PKC, as well as the phosphorylation of Akt and ERK1/2. Additionally, chrysin attenuated phosphorylation of molecules such as FcγRIIa, FAK, Akt, and GSK3β in platelet spreading on immobilized fibrinogen. CONCLUSIONS: Our findings indicate that chrysin suppresses not only integrin αIIbβ3-mediated "inside-out" signaling, but also the "outside-in" signal transmission. This im...