PS 13-25 MANGIFERIN PROTECTS AGAINST MYOCARDIAL INSULTS THROUGH MODULATION OF MAPK PATHWAY

Abstract

Objective: Revascularization following acute myocardial infarction leads to ischemia reperfusion injury which is associated with oxidative stress, apoptosis and inflammation leading to impaired cardiovascular function. Mangiferin is a major phytochemical and a polyphenolic antioxidant present in the bark, fruits, roots and leaves of Mangifera indica Linn (Anacardiaceae). It is known to modulate many biological targets in inflammation & oxidative stress. It also possesses anti-oxidant, anti-apoptotic; anti-atherogenic and anti-diabetic actions. Hence, we hypothesized that the antioxidative, antiinflammatory, and antiapoptotic effects of mangiferin may also be involved in the prevention of IR injury. The present study was designed to investigate whether mangiferin exerts protection against myocardial ischemia-reperfusion (IR) injury with a focus on the underlying mechanism. Design and Method: Male albino Wistar rats were divided into four groups namely sham, IR-control, Mangiferin-40+IR and Mangiferin 40 per se. Mangiferin was administered at a dose of 40 mg/kg, intraperitoneally for 15 days. On the 15th day, myocardial IR injury was induced by occluding the left anterior descending coronary artery for 45 minutes followed by reperfusion for 60 minutes. At the end of the surgical procedure, the rats were sacrificed, the hearts excised and processed. Results: IR-control rats showed significant cardiac dysfunction, raised serum cardiac injury markers, and a significant decrease in tissue antioxidants as compared to sham group. Histopathological examination of IR rats revealed myocardial necrosis, edema and inflammatory cells infiltration. Pretreatment with mangiferin significantly suppressed myocardial oxidative damage, maintained membrane integrity, and attenuated the levels of proinflammatory cytokines, pro-apoptotic proteins and TGF-β. Additionally, mangiferin significantly reduced the phosphorylation of p38, and JNK and enhanced phosphorylation of ERK1/2. Conclusions: Mangiferin protects against myocardial IR injury by alleviating oxidative stress mediated apoptosis and modulating MAPK mediated inflammation.