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

• Published in: Molecular nutrition & food research Vol. 60; no. 9; pp. 1984 - 1993
• Main Authors: Liu, Gang, Xie, Wen, He, Ao-Di, Da, Xing-Wen, Liang, Ming-Lu, Yao, Guang-qiang, Xiang, Ji-Zhou, Gao, Cun-ji, Ming, Zhang-Yin
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01-09-2016
• Subjects: Adult; Chrysin; Collagen - pharmacology; Dose-Response Relationship, Drug; Female; Flavonoids - pharmacology; Glycoprotein VI pathway; Humans; Integrin αIIbβ3; Male; Mitogen-Activated Protein Kinase 1 - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phospholipase C gamma - metabolism; Phosphorylation - drug effects; Platelet; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Syk Kinase - metabolism; Platelet; Chrysin; Integrin αIIbβ3; Glycoprotein VI pathway
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500801

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 implies that chrysin may represent a potential candidate for an antiplatelet agent.
Chrysin, a bioflavonoid compound found in high levels in propolis and in honey, possesses antiplatelet activity. We report that chrysin inhibits platelet aggregation, granule secretion, adhesion, and spreading. The mechanism by which it inhibits platelet functions was explored. Chrysin suppresses not only integrin αIIbβ3‐mediated “inside‐out” signaling, but also the “outside‐in” signal transmission.