Sanguinarine Attenuates Collagen-Induced Platelet Activation and Thrombus Formation

Abstract

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.

Platelet-Derived TGF (Transforming Growth Factor)-β1 Enhances the Aerobic Glycolysis of Pulmonary Arterial Smooth Muscle Cells by PKM2 (Pyruvate Kinase Muscle Isoform 2) Upregulation

“…Platelet allowed to rest for at least 30 minutes at 37 °C before use. 23,24 The procedure of isolating mice platelet was same as rats.…”

Integrating Network Pharmacology and Molecular Docking to Analyse the Potential Mechanism of action of Macleaya cordata (Willd.) R. Br. in the Treatment of Bovine Hoof Disease

“…There has been some evidence of a therapeutic role for SAN in hoof disease-related disorders. SAN can act on PI3K-Akt-GSK3β and Src (Tyr-416) to inhibit platelet activation and reduce thrombosis [70]. SAN inhibits VEGFinduced Akt phosphorylation to exert anti-angiogenic effects and plays an important role in arthritis [71,72].…”

Therapeutic effects and molecular mechanisms of natural products in thrombosis

“…Pterostilbene, a stilbene isolated from berries, can regulate "inside-out" signaling and "out-inside" signaling by affecting the activation of integrin αIIbβ3 and inhibiting the phosphorylation of integrin β3, Src, and FAK (Huang et al, 2021). Shu et al (2021) investigated the antithrombotic effect and platelet inhibition mechanism of sanguinarine, the results showed that sanguinarine can suppress the phosphorylation of integrin β3 and Src to inhibit integrin αIIbβ3 "out-inside" signaling. In addition, sanguinarine also reduced the phosphorylation of Syk-PLCγ2 and PI3K-Akt-GSK3β pathway.…”

“…In recent years, several natural products approved by the Food and Drug Administration (FDA) for the treatment of other diseases have been found to have antithrombotic activity. For example, sanguinarine, a benzophenanthridine alkaloid isolated from Macleaya cordata, is widely used to inhibit the growth of dental plaque Shu et al (2021). have shown that sanguinarine can inhibit collagen-induced platelet activation and significantly prolong the occlusion time in carotid injury mice at doses >5 mg/kg.…”