Exploring the cardioprotective role of metformin against isoproterenol-induced myocardial infarction using computational, cellular, and animal models

Despite significant advances in therapeutic techniques, Myocardial infarction (MI) is an important root cause of morbidity and death worldwide. Metformin (MET), a primary antidiabetic medication, has been studied for its possible cardioprotective properties. To evaluate metformin's protective role and underlying mechanisms against isoproterenol (ISO)-induced myocardial infarction utilizing Network Pharmacology combined with in vivo techniques. ISO-induced MI was established in male Sprague Dawley (SD) rats by administering ISO. Animals were administered metformin (100 mg/kg) for 14 days prior to ISO exposure. Network pharmacology helped to predict and identify potential targets and interactions of metformin in MI, and the pathway analysis. In vitro studies using H9C2 cardiomyoblasts provided preliminary evidence of metformin-mediated protection against ISO-induced cellular injury. Network pharmacology analysis identified 27 potential targets of metformin associated with MI, including 10 key hub genes. Gene Ontology (GO) and pathway enrichment analyses revealed the major biological processes and signaling pathways involved in the cardioprotective effects of metformin. In vitro, metformin exerted a dose-dependent protective effect against ISO-induced injury in H9C2 cells. In vivo results confirmed successful induction of MI, while metformin pretreatment significantly attenuated ISO-induced myocardial damage and modulated serum biochemical parameters. Metformin pretreatment significantly attenuated ISO-induced myocardial injury, as evidenced by reduced serum CK-MB, SGOT, SGPT, and TNF-α levels, along with improvement in cardiac histological alterations. These findings highlight the potential of metformin as a cardioprotective candidate; however, further validation through advanced preclinical studies and clinical trials is required.