Therapeutic Potential of Myrica esculenta Fruit Extract in Attenuating Myocardial Damage in an Isoproterenol-Induced Experimental Model of Myocardial Infarction in Mice

Myrica esculenta Buch. -Ham. ex D. Don (Myricaceae), commonly known as Kaphal, is widely used in Indian traditional medicine; however, its cardioprotective potential remains inadequately explored. The present study aimed to evaluate the cardioprotective effects of the methanolic extract of M. esculenta fruit (MEMEF) in an isoproterenol (ISO)-induced myocardial infarction (MI) model in male Swiss albino mice. Mice were orally pretreated with MEMEF (200 and 400 mg/kg) for 30 days, followed by ISO administration (100 mg/kg, s.c.) for two consecutive days. Atenolol (10 mg/kg) served as the standard drug. Serum cardiac injury markers, lipid profile, myocardial histopathology, mRNA expression of Nrf2, HO-1, cTnI, Anp, and Bnp, and protein expression of Nrf2 and cTnI were evaluated. Phytochemical profiling was performed using LC-MS, and molecular docking analysis was conducted to predict ligand–target interactions. ISO administration significantly elevated serum CK-MB, CK-NAC, cTnI, and LDH levels compared with controls. MEMEF pretreatment, particularly at 400 mg/kg, markedly reduced these markers, with effects comparable to atenolol. MEMEF also improved lipid profile by reducing total cholesterol and triglycerides while increasing HDL levels. At the molecular level, MEMEF upregulated Nrf2 and HO-1 and downregulated Anp, Bnp, and cTnI expression. Western blot analysis corroborated increased Nrf2 and decreased cTnI protein levels. Histopathological examination revealed preservation of myocardial architecture in MEMEF-treated groups. LC-MS identified esculetin, quercetin, linoleic acid, caffeic acid, and resveratrol, with esculetin showing the strongest binding affinity in docking studies. Myrica esculenta fruit extract confers significant protection against ISO-induced myocardial injury through antioxidant activation, lipid modulation, and molecular regulation, supporting its potential as a cardioprotective nutraceutical.