Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats

• Published in: PloS one Vol. 7; no. 12; p. e52013
• Main Authors: Yu, Wei, Wu, Jiliang, Cai, Fei, Xiang, Jizhou, Zha, Wenliang, Fan, Dan, Guo, Shuang, Ming, Zhangyin, Liu, Chao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.12.2012; Public Library of Science (PLoS)
• Subjects: Aberration; Abnormalities; Accumulation; Advanced glycosylation end products; Age; AKT protein; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bax protein; Bcl-2 protein; Biochemical tests; Biological products; Biology; Cardiomyopathy; Cardiovascular disease; Caspase; Caspase-3; Cell death; Cell Death - drug effects; Cell Death - genetics; Curcumin; Curcumin - pharmacology; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetic Cardiomyopathies - drug therapy; Diabetic Cardiomyopathies - genetics; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - pathology; Echocardiography; Energy intake; Enzyme-linked immunosorbent assay; Enzymes; Fibrosis; Fibrosis - drug therapy; Fibrosis - genetics; Fibrosis - metabolism; Fibrosis - pathology; Gene expression; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Glycosylation; Heart; Heart - drug effects; Heart diseases; Hyperglycemia; Hypertrophy; IL-1β; Inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Laboratory animals; Male; Medicine; Metabolic disorders; Metabolism; Myocardial diseases; Myocardium - metabolism; Myocardium - pathology; NAD(P)H oxidase; Oxidases; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - genetics; Pharmacology; Phosphorylation; Phosphorylation - drug effects; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rac1 protein; Rats; Rats, Wistar; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Science; Signal transduction; Signaling; Studies; Ultrastructure; Ventricular Dysfunction, Left - drug therapy; Ventricular Dysfunction, Left - genetics; Ventricular Dysfunction, Left - metabolism; Ventricular Dysfunction, Left - pathology; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0052013

Diabetic cardiomyopathy (DCM), characterized by myocardial structural and functional changes, is an independent cardiomyopathy that develops in diabetic individuals. The present study was sought to investigate the effect of curcumin on modulating DCM and the mechanisms involved. An experimental diabetic rat model was induced by low dose of streptozoticin(STZ) combined with high energy intake on rats. Curcumin was orally administrated at a dose of 100 or 200 mg · kg(-1) · d(-1), respectively. Cardiac function was evaluated by serial echocardiography. Myocardial ultrastructure, fibrosis area and apoptosis were assessed by histopathologic analyses. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. Inflammatory factors were detected by ELISA, and interrelated proteins were measured by western blot. Rats with DCM showed declined systolic myocardial performance associated with myocardial hypertrophy and fibrosis, which were accompanied with metabolism abnormalities, aberrant myocardial enzymes, increased AGEs (advanced glycation end products) accumulation and RAGE (receptor for AGEs) expression, elevated markers of oxidative stress (MDA, SOD, the ratio of NADP(+)/NADPH, Rac1 activity, NADPH oxidase subunits expression of gp91(phox) and p47(phox) ), raised inflammatory factor (TNF-α and IL-1β), enhanced apoptotic cell death (ratio of bax/bcl-2, caspase-3 activity and TUNEL), diminished Akt and GSK-3β phosphorylation. Remarkably, curcumin attenuated myocardial dysfunction, cardiac fibrosis, AGEs accumulation, oxidative stress, inflammation and apoptosis in the heart of diabetic rats. The inhibited phosphorylation of Akt and GSK-3β was also restored by curcumin treatment. Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of DCM, and perhaps other cardiovascular disorders, by attenuating fibrosis, oxidative stress, inflammation and cell death. Furthermore, Akt/GSK-3β signaling pathway may be involved in mediating these effects.