Stachydrine exhibits a novel antiplatelet property and ameliorates platelet-mediated thrombo-inflammation
Xianting Sun, Zhou Meng, Jun Pu, Ting Wang
Abstract
BACKGROUND: Platelets are versatile anucleate cells involved in thrombosis as well as inflammation. Stachydrine (STA), a major bioactive compound extracted from Motherwort, has multiple pharmacological properties. Nevertheless, the significance of STA in platelet regulation and whether STA could ameliorate platelet-mediated thrombo-inflammation still remain elusive. METHODS: injury-induced carotid/mesenteric thrombosis and collagen/epinephrine-induced pulmonary thromboembolism model were used to explore whether STA could regulate thrombosis in vivo. Furthermore, a cecal ligation and puncture-induced sepsis model was employed to investigate the role of STA in thrombo-inflammatory diseases. RESULTS: STA markedly suppressed platelet activation represented by aggregation, secretion, αIIbβ3-mediated signaling events and calcium mobilization, etc. by inhibiting agonists-induced activation signaling and potentiating cGMP-dependent inhibitory signaling. Mice receiving STA-treated platelets were less susceptible to thrombosis in vivo. In addition, decreased platelet-neutrophil interactions including platelet-neutrophil aggregates and neutrophil extracellular traps, and alleviative sepsis-induced multiorgan damage were observed due to STA-mediated platelet inhibition. CONCLUSION: This study suggested the potential therapeutic role of STA in thrombotic and thrombo-inflammatory disorders.