Identification of salvianolic acid A as an ADP receptor-selective and Gq/IP3 pathway-mediated anti-platelet component in Qishen Yiqi

Background Antiplatelet therapy is crucial for preventing and treating cardio-cerebrovascular diseases. However, adverse events related to thrombosis or bleeding have been reported in instances of treatment with glycoprotein IIb/IIIa antagonists. It is anticipated that developing new selective platelet inhibitors with high anti-thrombotic efficiency and minimal hemorrhagic side effects is feasible. Qishen Yiqi Dripping Pill (QSYQ), an approved drug for ischemic heart disease, was studied for its anti-thrombotic effects. Methods and results Employing a microplate-based platelet aggregation assay, we systematically evaluated QSYQ and its medicinal components, chemical fractions, and compounds from the active fractions, identifying Salvianolic acid A (SAA) as one of the major active components for platelet inhibition. Our findings revealed that SAA decreased platelet [Ca 2+ ] i via the G q /IP 3 pathway without affecting cAMP levels. Furthermore, 20 mg/kg SAA reduced thrombus formation in a ferric chloride (FeCl 3 )-induced thrombotic model in vivo, suggesting the pharmacological significance of SAA in QSYQ. Conclusion This study identified SAA as one of the pharmacologically active anti-platelet components in QSYQ and revealed that its mechanism of action operates via the G q /IP 3 signaling pathway.