Cardiovascular diseases (CVDs) remain the principal cause of death in both developed and developing countries. The present study was intended to appraise the nutraceutical inherent of HPLC standardized Spinacia oleracea methanolic leaf extract (SoLE) in isoproterenol (ISO) induced male albino Wistar rats via activation of pro-inflammatory signaling pathway that drives myocardial necrosis. Biochemical analysis of ISO injected rats showed significant alterations in the activities of homocysteine, paraoxonase, lecithin cholesterol acyltransferase, C-reactive protein, myeloperoxidase and caspase-3 which were further confirmed by the histopathological examination. In addition, it also flaunted a significant increase in pro-inflammatory cytokines, such as TNF-α, IL-1β, IL-6 in ISO administered rats when compared with normal control rats. Pretreatment with SoLE (100, 200, and 300mg/kg bw) along with positive control gallic acid, significantly prevented all the adverse effects in ISO administered rats in a dose dependent manner. These results also reiterated the expected amelioration of myocardial necrosis in ISO induced MI rats conveying anti-atherogenic, anti-apoptotic and anti-inflammatory activities of SoLE.