Abstract
Objective: Myocardial infarction continues to be associated with high morbidity and mortality worldwide despite the availability of current therapeutic modalities. Morin, a bioflavonoid has known to possess good antioxidant, immunomodulatory and anti-apoptotic properties in previous studies. Hence, this study evaluated the cardioprotective mechanism(s) of Morin against isoproterenol induced myocardial necrosis in rats. Rationale: In this study, the ability of Morin to protect heart against isoproterenol (ISO) induced oxidative stress and myocardial infarction was evaluated. Design and method: Male albino Wistar rats were divided into five groups (8 rats in each group) i.e., I (normal), II (ISO-control), III, IV and V (morin 20, 40 and 80 mg/kg respectively). Groups III, IV and V were treated orally with daily doses of Morin accordingly for 28 days. On 26th and 27th day, a single injection of isoproterenol was injected (85 mg/kg s.c.) at 24 h interval to induce myocardial necrosis in group II, III, IV and V. On 28th day, hemodynamic parameters were evaluated, animals were euthanised and heart was excised for measurement of various parameters. Results: In ISO-control rats, there was deterioration of hemodynamic parameters, decreased anti-oxidants levels, increased cardiac injury markers and pro-inflammatory cytokines (TNF-alpha and IL-6). Also, there was increased level of Bax, Caspase-3, p-JNK, p-38 and NF-kappaB and decreased expression of Bcl-2 and p-ERK1/2 in ISO-C group. Morin dose-dependently improved hemodynamic profile, increased anti-oxidant levels, normalized myocardial architecture and reduced inflammatory markers and apoptosis. Furthermore, immunoblot analysis of MAPK pathway proteins demonstrated the mechanism responsible for anti-apoptotic and anti-inflammatory potential of morin. Conclusions: Thus, this study substantiated the beneficial effect of Morin by virtue of its modulation of MAPK pathway in myocardial injury.
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