Sanguinarine Attenuates Collagen-Induced Platelet Activation and Thrombus Formation
Dan Shu,
Ying Zhu,
Meng Lu,
Ao-Di He,
Jiang-Bin Chen,
Ding-Song Ye,
Yue Liu,
Xiang-Bin Zeng,
Rong Ma,
Zhang-Yin Ming
Affiliations
Dan Shu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Ying Zhu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Meng Lu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Ao-Di He
Department of Physiology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China
Jiang-Bin Chen
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Ding-Song Ye
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Yue Liu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Xiang-Bin Zeng
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Rong Ma
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
Zhang-Yin Ming
Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong, University of Science and Technology, 13 Hangkong Road, Wuhan 430030, China
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.