Abstract

Aberrant activation of platelets has a critical role in thrombotic vascular events, including atherosclerosis, arterial thrombosis and myocardial infarction. The process of platelet activation is associated with multiple intracellular signaling pathways, including the phosphoinositide3‑kinase/AKT serine/threonine kinase (Akt) pathway. The well‑known medicinal herb RhizomaLigusticumWallichii (RLW) has long been used in China to clinically treat various cardiovascular disorders. As the most pharmacologically active component of RLW, ligustrazine has been demonstrated to possess a potent antiplatelet activity. However, the precise mechanisms mediating the bioactivities of ligustrazine have not been thoroughly elucidated. The present study evaluated the effects of ligustrazine hydrochloride (LH; the clinical‑grade form of ligustrazine) on platelet activation and investigated the underlying molecular mechanisms. Invitro and exvivo platelet activation models were used, established by stimulating rat platelet‑rich plasma either with the platelet activator adenosine diphosphate (ADP) or with the specific Akt pathway activator insulin‑like growth factor‑1 (IGF‑1). The results demonstrated that treatment with LH significantly and dose‑dependently inhibited ADP‑induced platelet aggregation, in addition to thromboxaneA2 (TXA2) secretion and intracellular Ca2+ mobilization in platelets, invitro and exvivo. In addition, LH markedly suppressed ADP‑induced Akt phosphorylation invitro and exvivo. Furthermore, LH markedly inhibited IGF‑1‑induced Akt phosphorylation, platelet aggregation, TXA2 formation and Ca2+ mobilization invitro. Finally, LH was able to reverse adrenaline‑induced shortening of bleeding time. Taken together, these results suggested that ligustrazine possesses a broad range of antiplatelet activities without apparent hemorrhagic side-effects, and suppression of Akt signaling may be one of the mechanisms by which ligustrazine exerts its antiplatelet activities.

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