Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025
Shen Yuan Yi Qi Huo Xue capsules inhibit neutrophil NETosis by regulating the PAD4/NLRP3 signaling pathway to prevent heart failure after myocardial infarction.
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Lian Yan-Jie, Zhang He-Yi, Liu Hong-Xu, Shang Ju-Ju, Lai Xiao-Lei, Xing Wen-Long, Li Si-Nai
Аннотация
BACKGROUND: Heart failure (HF) is a severe, end-stage condition resulting from various cardiac diseases, with ischemic heart failure (IHF) being a common etiology caused by ischemia. Shen Yuan Yi Qi Huo Xue Capsules (SYYQ) is a traditional Chinese medicine (TCM) formulation known for its anti-thrombotic and myocardial protective effects. Nonetheless, experimental evidence and mechanistic insights into its role in preventing IHF remain limited.
PURPOSE: To investigate whether SYYQ reduces post-myocardial infarction (MI) inflammation and cardiac remodeling by inhibiting NETosis and reducing neutrophil activation.
METHODS: C57/B6J mice were randomly divided into Sham group, Model group, SYYQ-l, SYYQ-M, SYYQ-H, and Captopril group. MI model was induced by left anterior descending coronary artery ligation in Model group, while Sham group underwent sham surgery. Active compounds in SYYQ were identified using UPLCHRMS. Cardiac function and morphology were assessed using echocardiography, HE staining, Masson's trichrome. ELISA was used to measure myocardial injury markers and inflammatory cytokine expression. Whole blood cell counts assessed neutrophil variations. The mechanism of action of SYYQ was evaluated using Western blot and qPCR, and immunofluorescence. Meanwhile, the PAD4-/- MI mouse Model was constructed and randomly divided into the model group and the SYYQ group. The effect of SYYQ on the expression of key proteins in the occurrence of NETosis was further evaluated by Western blot. The effect of SYYQ was further verified through in vitro experiments.
RESULTS: The present study demonstrated that SYYQ improves cardiac function, myocardial microcirculation, and serum myocardial injury markers in MI mice. It reduces inflammatory cell infiltration in damaged myocardial tissue and normalizes elevated levels of NETosis by decreasing neutrophil entry into circulation. Western blot and qPCR results showed that SYYQ inhibits key proteins associated with NETosis including PAD4, NLRP3, Caspase-1, and gasdermin D (GSDMD). Importantly, SYYQ may target PAD4 to inhibit NETosis by suppressing PAD4 and downstream NLRP3, Caspase-1, and GSDMD protein expression levels in neutrophils.
CONCLUSION: SYYQ may inhibit neutrophil NETosis after MI, thereby preventing the massive entry of neutrophils into circulation, reducing post-MI inflammation and cardiac remodeling, and improving heart function simultaneously.
PURPOSE: To investigate whether SYYQ reduces post-myocardial infarction (MI) inflammation and cardiac remodeling by inhibiting NETosis and reducing neutrophil activation.
METHODS: C57/B6J mice were randomly divided into Sham group, Model group, SYYQ-l, SYYQ-M, SYYQ-H, and Captopril group. MI model was induced by left anterior descending coronary artery ligation in Model group, while Sham group underwent sham surgery. Active compounds in SYYQ were identified using UPLCHRMS. Cardiac function and morphology were assessed using echocardiography, HE staining, Masson's trichrome. ELISA was used to measure myocardial injury markers and inflammatory cytokine expression. Whole blood cell counts assessed neutrophil variations. The mechanism of action of SYYQ was evaluated using Western blot and qPCR, and immunofluorescence. Meanwhile, the PAD4-/- MI mouse Model was constructed and randomly divided into the model group and the SYYQ group. The effect of SYYQ on the expression of key proteins in the occurrence of NETosis was further evaluated by Western blot. The effect of SYYQ was further verified through in vitro experiments.
RESULTS: The present study demonstrated that SYYQ improves cardiac function, myocardial microcirculation, and serum myocardial injury markers in MI mice. It reduces inflammatory cell infiltration in damaged myocardial tissue and normalizes elevated levels of NETosis by decreasing neutrophil entry into circulation. Western blot and qPCR results showed that SYYQ inhibits key proteins associated with NETosis including PAD4, NLRP3, Caspase-1, and gasdermin D (GSDMD). Importantly, SYYQ may target PAD4 to inhibit NETosis by suppressing PAD4 and downstream NLRP3, Caspase-1, and GSDMD protein expression levels in neutrophils.
CONCLUSION: SYYQ may inhibit neutrophil NETosis after MI, thereby preventing the massive entry of neutrophils into circulation, reducing post-MI inflammation and cardiac remodeling, and improving heart function simultaneously.