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Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats.

Abstract

OBJECTIVES

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.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

    , , , , , , ,

    Source

    PloS one 7:12 2012 pg e52013

    MeSH

    Animals
    Apoptosis
    Cell Death
    Curcumin
    Diabetes Mellitus, Experimental
    Diabetic Cardiomyopathies
    Fibrosis
    Glycogen Synthase Kinase 3
    Glycogen Synthase Kinase 3 beta
    Heart
    Inflammation
    Male
    Myocardium
    Oxidative Stress
    Phosphorylation
    Proto-Oncogene Proteins c-akt
    Rats
    Rats, Wistar
    Receptor for Advanced Glycation End Products
    Receptors, Immunologic
    Ventricular Dysfunction, Left

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23251674

    Citation

    Yu, Wei, et al. "Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats." PloS One, vol. 7, no. 12, 2012, pp. e52013.
    Yu W, Wu J, Cai F, et al. Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PLoS ONE. 2012;7(12):e52013.
    Yu, W., Wu, J., Cai, F., Xiang, J., Zha, W., Fan, D., ... Liu, C. (2012). Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. PloS One, 7(12), pp. e52013. doi:10.1371/journal.pone.0052013.
    Yu W, et al. Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats. PLoS ONE. 2012;7(12):e52013. PubMed PMID: 23251674.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Curcumin alleviates diabetic cardiomyopathy in experimental diabetic rats. AU - Yu,Wei, AU - Wu,Jiliang, AU - Cai,Fei, AU - Xiang,Jizhou, AU - Zha,Wenliang, AU - Fan,Dan, AU - Guo,Shuang, AU - Ming,Zhangyin, AU - Liu,Chao, Y1 - 2012/12/14/ PY - 2012/04/18/received PY - 2012/11/08/accepted PY - 2012/12/20/entrez PY - 2012/12/20/pubmed PY - 2013/9/6/medline SP - e52013 EP - e52013 JF - PloS one JO - PLoS ONE VL - 7 IS - 12 N2 - OBJECTIVES: 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23251674/Curcumin_alleviates_diabetic_cardiomyopathy_in_experimental_diabetic_rats_ L2 - http://dx.plos.org/10.1371/journal.pone.0052013 DB - PRIME DP - Unbound Medicine ER -