Abstract:The objective of this study is to evaluate the effect of ethyl acetate extract of Commiphora mukul (guggul) (EACM) in streptozotocin (STZ) induced diabetic cardiomyopathy in rats. Diabetes was induced in rats with STZ (45 mg/kg, i.p). The animals were divided in four groups: I-normal control, II-diabetic control, III-diabetic animals treated with EACM (400 mg/kg/day, p.o) and IV-normal animals treated with EACM (400 mg/kg/day, p.o).Cardiomyopathy developed after eight weeks of induction of diabetes. The biochemical parameters (glucose, triglycerides, cholesterol, LDL, HDL, CKMB, LDH) were evaluated at regular intervals. The hemodynamic measurements (LVDEP, Mean BP, Max dP/dT, Min dP/dT, ST segment and QT interval) were done on the 8 th week. Standardized EACM contained 3.36% w/w of guggulsterones. There were significant changes observed in the biochemical, hemodynamic and histological parameters of diabetic animals indicating induction of diabetic cardiomyopathy, whereas diabetic animals treated with EACM for eight weeks showed significant improvement in these parameters which serve as diabetic and cardiac markers. The present study reveals that EACM is effective in preventing diabetes induced myocardial dysfunction. This might be due to its efficacy in (a) normalizing the metabolic disturbances by acting as Farnesoid X receptor antagonist (FXR) or PPAR-alpha and PPAR-gamma agonist thereby regulating the lipid and glucose metabolism, (b) having a cardioprotective effect through various mechanisms such as regulation of endothelial nitric oxide synthase (eNOS), angiotensin type 2 receptor expression etc or (c) both. Thus, guggul might be a promising candidate to be evaluated for clinical efficacy in diabetic patients for the prevention of cardiomyopathy.