| Summary: | Aim of the study: This study aims to identify the effects of Nuanxinkang (NXK) on inflammation and pyroptosis post-MI and understand the underlying mechanisms. Materials and methods: Left Anterior Descending (LAD) coronary artery ligation was used to induce MI in mice. NXK or Captopril were orally administered 3 days after surgery for 4 weeks. Cardiac function, as well as infarct size, was detected by echocardiography, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Hematoxylin and Eosin (H&E) staining. Inflammatory mediators were measured by flow cytometry, real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF). Pyroptosis-related protein expressions were determined through Western blot (WB). Intracellular Ca2+ measurements were conducted in bone marrow derived macrophages (BMDM) to detect calcium influx. Molecular docking (MD) was applied to define the candidate ingredients in NXK that regulate Piezo1. Results: NXK increased the ratio of heart or lung and body weight in mice post-MI. TTC and H&E staining infarct size and myocardial damage. The results obtained through echocardiography suggest that NXK remarkably enhanced heart function. Immunofluorescence of F4/80 and flow cytometry results demonstrated that NXK suppressed inflammatory infiltration. Molecular docking showed that Piezo1 had correlation with NXK. Intracellular Ca2+ measurements suggest that NXK inhibit Yoda1-evoked Piezo1 activation. Furthermore, NXK treatment significantly suppressed Piezo1-mediated pyroptosis in vivo and in vitro. Conclusions: The present study indicates that NXK may prevent ventricular remodeling post-MI through regulation of the Piezo1-mediated pyroptosis. Furthermore, the study provides a potential strategy for attenuating NLRP3-inflmmasome activation in the context of ventricular remodeling post-MI using NXK.
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