Sanguinarine Attenuates Collagen-Induced Platelet Activation and Thrombus Formation
| Autor: | Zhang-Yin Ming, Rong Ma, Ying Zhu, Meng Lu, Ding-Song Ye, Dan Shu, Yue Liu, Xiang-Bin Zeng, Ao-Di He, Jiang-Bin Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 Integrin Medicine (miscellaneous) 030204 cardiovascular system & hematology Pharmacology antithrombotic glycoprotein VI pathway General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Sanguinarine Platelet Platelet activation Biology (General) platelet biology Chemistry 030104 developmental biology biology.protein Phosphorylation Signal transduction GPVI sanguinarine integrin αIIbβ3 Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biomedicines Volume 9 Issue 5 Biomedicines, Vol 9, Iss 444, p 444 (2021) |
| ISSN: | 2227-9059 |
| Popis: | Sanguinarine, a benzophenanthridine alkaloid, has been described to have an antiplatelet activity. However, its antithrombotic effect and the mechanism of platelet inhibition have not thoroughly been explored. The current study found that sanguinarine had an inhibitory effect on thrombus formation. This inhibitory effect was quite evident both in the flow-chamber assays as well as in a murine model of FeCl3-induced carotid artery thrombosis. Further investigations also revealed that sanguinarine inhibited the collagen-induced human platelet aggregation and granule release. At the same time, it also prevented platelet spreading and adhesion to immobilized fibrinogen. The molecular mechanisms of its antiplatelet activity were found to be as follows: 1. Reduced phosphorylation of the downstream signaling pathways in collagen specific receptor GPVI (Syk-PLCγ2 and PI3K-Akt-GSK3β) 2. Inhibition of collagen-induced increase in the intracellular Ca2+ concentration ([Ca2+]i) 3. Inhibition of integrin αIIbβ3 outside-in signaling via reducing β3 and Src (Tyr-416) phosphorylation. It can be concluded that sanguinarine inhibits collagen-induced platelet activation and reduces thrombus formation. This effect is mediated via inhibiting the phosphorylation of multiple components in the GPVI signaling pathway. Current data also indicate that sanguinarine can be of some clinical value to treat cardiovascular diseases involving an excess of platelet activation. |
| Databáze: | OpenAIRE |
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