title: Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Cai
authors.forename: Jizhou
authors.initials: J
authors.lastname: Xiang
authors.forename: Wenliang
authors.initials: W
authors.lastname: Zha
authors.forename: Dan
authors.initials: D
authors.lastname: Fan
authors.forename: Shuang
authors.initials: S
authors.lastname: Guo
authors.forename: Zhangyin
authors.initials: Z
authors.lastname: Ming
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin