Piperazine ferulate protects against cardiac ischemia/reperfusion injury in rat via the suppression of NLRP3 inflammasome activation and pyroptosis

Piperazine ferulate (PF) has been reported to protect cardiac from ischemia/reperfusion injury to achieve myocardial protection. NLRP3 inflammasome activation-mediated pyroptosis has been shown to the involvement in myocardial ischemia-reperfusion injury (MI/RI). Increasing evidence suggested that PF is used for cardiovascular diseases, whereas its protection of MI/RI and the mechanism are not fully understood. Rats' model of MI/RI was subjected by occlusion of the left anterior descending (LAD) coronary artery for 30 min followed by 120 min of reperfusion to investigate whether PF exhibited cardiac protection via modulating the NLRP3 inflammasome-mediated pyroptosis. Rats were intragastrically administrated with PF (100 mg/kg) for 7 consecutive days prior to I/R surgery. The results showed that PF remarkedly elevated left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and decrease mitral early diastolic flow velocity/late diastolic flow velocity (E/A) of I/R injury rats compared with the I/R group. Besides, MI/RI contributes to increasing the cardiac infarction size and aggravates the myocardial injury as well as causes inflammation, whereas these detrimental alterations were ameliorated by PF pretreatment. Mechanically, the protein and gene expression levels of NLRP3, ASC, GSDMD, IL-Iβ and caspase-1 in the PF-treated group were lower than those of the I/R group, which indicates that PF can evidently suppress the I/R-triggered NLRP3 inflammasome activation and pyroptosis in the heart. These results indicated that PF could prevent I/R-induced cardiac damages and cardiac dysfunction in the rats induced by I/R challenge, and it might be a potential therapeutic strategy for the treatment of ischemic heart disease.