Harnessing flavonoids as innovative agents for the modulation of platelet activation and thrombotic disorders

Thrombotic diseases remain a leading cause of global mortality and a significant public health burden. While conventional antiplatelet and anticoagulant therapies are cornerstone strategies, their clinical application is frequently hindered by a significant risk of hemorrhagic complications and limited efficacy in certain patient populations. Consequently, there is an urgent need for safer and more effective antithrombotic agents. Flavonoids, a diverse class of plant-derived polyphenols, have garnered considerable attention due to their potent antiplatelet and antithrombotic activities coupled with a favorable safety profile. This review systematically examines the latest advancements in the therapeutic effects of flavonoids on thromboembolic disorders and elucidates their underlying molecular mechanisms. Evidence suggests that flavonoids function as multi-target inhibitors. They exert antithrombotic effects by regulating platelet activation through interfering with multiple signaling pathways, including the ADP-mediated P2Y1/P2Y12 cascade, cyclic nucleotide (cAMP/cGMP) signaling, and the collagen pathway. Additionally, these compounds inhibit the coagulation cascade by targeting key proteases including thrombin. This review provides an evidence-based roadmap for the development of flavonoid-derived therapies, aiming to facilitate their translation into clinical interventions for the effective management of thrombotic diseases.