Abstract
BACKGROUND: Arterial thrombotic diseases are leading causes of global morbidity and mortality, primarily driven by platelet hyperactivity. Qiliqiangxin capsules (QLQX), a traditional Chinese medicine approved in China for the treatment of heart failure, have exhibited potential benefits in reducing cardiovascular death. However, its direct effects on platelet activation and thrombosis remain unclear. METHODS AND RESULTS: Ex vivo platelet function assays demonstrated that oral QLQX inhibited agonist‑induced aggregation in platelet‑rich plasma (PRP) from chronic heart failure (CHF) patients and dose-dependently suppressed washed platelet aggregation in wild‑type mice. In parallel, QLQX administration attenuated platelet spreading and clot retraction in washed platelets from both patients with CHF and wild-type mice, and reduced ex vivo thrombus formation area in a microfluidic whole‑blood perfusion under arterial shear stress. Flow cytometry analysis revealed that QLQX did not affect the surface expression levels of the major platelet receptors, but reduced the activation of αIIbβ3 and P-selectin exposure induced by thrombin in mouse platelets. In vivo experiments demonstrated that QLQX treatment inhibited FeCl₃-induced thrombus formation in mesenteric arterioles, reduced collagen/epinephrine-induced pulmonary embolism, and mitigated microvascular thrombosis during myocardial ischemia-reperfusion (I/R) injury, without increasing bleeding in mice. RNA sequencing of platelets from QLQX- versus vehicle-treated mice identified differentially expressed genes enriched in the calcium signaling pathway, and functional assays demonstrated that QLQX inhibited agonist-induced platelet Ca²⁺ influx and PKC phosphorylation. CONCLUSION: QLQX inhibits platelet activation and thrombosis by targeting Ca²⁺ influx and PKC signaling, supporting its potential therapeutic value in preventing thrombotic complications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12959-025-00823-8.