期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 152, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113184
关键词
Stachydrine; Platelet activation; Thrombosis; Sepsis; Thromboinflammation
资金
- National Natural Science Founda-tion of China [81570177]
This study demonstrates the significant role of STA in regulating platelet activation and reducing thrombo-inflammation. STA inhibits platelet activation and decreases platelet-neutrophil interactions, thereby attenuating thrombus formation and thrombo-inflammatory-induced multiorgan damage.
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: Human platelets were used to assess the regulatory effects of STA on platelet activation and interactions with neutrophils in vitro. FeCl3 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, alpha IIb beta 3-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.
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