Taxifolin Inhibits Platelet Activation and Thrombosis by Regulating the PI3K/Akt and MAPK Signaling Pathways.

Excessive platelet activation plays a pivotal role in the development of cardiovascular disease. Taxifolin is a natural dihydroflavonol compound with antioxidant properties. However, its mechanism of action on platelets and thrombosis remains unclear. Therefore, this study aimed to investigate the effects of taxifolin on platelet function and thrombus formation and identify its potential targets. The results revealed that taxifolin inhibited platelet aggregation induced by various agonists, such as ADP, collagen, thrombin, U46619, and convulxin. Moreover, it also limited platelet adhesion to collagen and the synthesis of TXA. Additionally, it impeded platelet integrin αIIbβ3 ''outside-in '' signaling, which is crucial for stable clot formation. In animal models, taxifolin showed promising results in preventing pulmonary embolism and arterial thrombosis. More importantly, taxifolin did not cause significant side effects. Network pharmacology analysis suggested that taxifolin may exert its effects through key targets involved in platelet aggregation and thrombus formation, such as MAPK1, AKT1, SRC, PIK3R1, and MAPK8. Meanwhile, molecular docking studies confirmed the interaction between taxifolin and MAPK1. Furthermore, taxifolin inhibited the phosphorylation of ERK, p38, JNK, and Akt, key proteins in the MAPK and PI3K/Akt signaling pathways. Overall, taxifolin demonstrated potential as an antiplatelet and antithrombotic agent, acting through multiple pathways and targets.