MOLECULAR UNDERSTANDING TOWARDS ANTI-INFLAMMATORY ROLE OF MORIN IN ISOPROTERENOL INDUCED MYOCARDIAL NECROSIS IN MURINE MODEL

Objective: Present study was aimed to investigate the cardioprotective effects of Morin, a bioflavonoid against isoproterenol-induced myocardial necrosis in male albino Wistar rat model via modulation of inflammatory pathway. Design and method: Acclimatized rats were divided into 5 groups (n=8) i.e., Normal control, ISO-control, Morin20+ISO, Morin40+ISO, and Morin80+ISO. Morin was administered for 28 days as pretreatment at doses of 20, 40, and 80 mg/kg respectively. On the 26th and 27th day, isoproterenol was injected at 85 mg/kg s.c. at 24 h intervals to induce myocardial necrosis in ISO-control and morin pre-treated groups. On day 28 animals were anesthetized, tracheostomy was done and the carotid artery was ligated and connected to the pressure transducers to measure hemodynamic parameters. After measuring left ventricular pressures, the rats were sacrificed using overdose of anesthesia, and blood was withdrawn. Levels of cardiac injury markers, pro-inflammatory cytokines, hemodynamic and anti-oxidant parameters were determined. Results: Oral administration of morin significantly prevented the isoproterenol-induced inflammation that led to myocardial necrosis. There was a marked reduction in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6), Bax, Caspase-3, p-JNK, p-38, NF-kappa B, and increased expression of Bcl-2 and p-ERK1/2 in treatment groups compared to ISO-Control. Besides, immunoblot analysis of MAPK pathway proteins illustrated the mechanism behind the anti-apoptotic and anti-inflammatory action of morin. Conclusions: The cardioprotective effect of morin can be ascribable to the modulation of MAPK pathway in isoproterenol-induced myocardial inflammation.