AbstractContextPunicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear.ObjectiveThese studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI.Materials and methodsMolecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1β (IL-1β) and IL-18 were evaluated.ResultsPunicalagin had binding activities with NLRP3 (Vina score, −5.8), caspase-1 (Vina score, −6.7), and GSDMD (Vina score, −6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p< 0.01), and inhibit cardiomyocyte apoptosis (p< 0.01). Furthermore, punicalagin could inhibit the overexpression of NLRP3, caspase-1, and GSDMD via immunohistochemistry (p< 0.01). Punicalagin inhibited the protein levels of NLRP3, caspase-1, ASC, GSDMD, and GSDMD-N (p< 0.05,p< 0.01). Punicalagin reduced the mRNA expression of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 (p< 0.05,p< 0.01).ConclusionsPunicalagin may provide a useful treatment for the future myocardial protection.