Puerarin attenuates myocardial ischemia‑reperfusion injury by inhibiting myocardium pyroptosis via the NRF2/HO‑1 signaling pathway.

Abstract

Myocardial ischemia‑reperfusion injury (MIRI) can trigger inflammatory responses and cause pyroptosis. Puerarin (Pue), as a traditional medicine, exhibits potential value in cardiac protection. However, the mechanism by which Pue regulates pyroptosis in MIRI remains to be fully elucidated. The present study aimed to explore the cardioprotective effects of Pue against MIRI and reveal the underlying mechanisms of these effects. Sprague‑Dawley rats were used to establishmodels of MIRI, while H9C2 rat embryonic cardiomyocytes were employed asmodels. Echocardiography was performed to measure cardiac function. Triphenyltetrazolium chloride/Evans blue staining, hematoxylin‑eosin staining, Masson's trichrome staining and immunohistochemistry were employed to assess the pharmacodynamic effects of Pue. The expression of molecules related to pyroptosis, such as nuclear factor E2‑related factor 2 (NRF2) and heme oxygenase‑1 (HO‑1) were detected by immunofluorescence, Hoechst 33342/PI staining, reverse transcription‑quantitative PCR and western blot analyses. The results of the present study showed that Pue pretreatment reduced the area of myocardial infarction and decreased the expression of pyroptosis‑related molecules. Additionally, Pue was shown to reverse H2O2‑induced mitochondrial dysfunction in cardiomyocytes and inhibit nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3)/caspase‑1/gasdermin D (GSDMD)‑mediated pyroptosis. Pue was also shown to stimulate the nuclear translocation of NRF2 and increase the expression of HO‑1. Furthermore, Pue further demonstrated its anti‑pyroptotic effects by activating the NRF2/HO‑1 pathway. The present study revealed that Pue can protect injured myocardium after MIRI by inhibiting NLRP3/caspase‑1/GSDMD‑mediated pyroptosis. The mechanism of action for these cardioprotective effects relied upon downregulation of the NRF2/HO‑1 signaling pathway. The findings of the present study provided a novel strategy for the clinical application of puerarin in the treatment of MIRI.