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Rutin alleviates diabetic cardiomyopathy and improves cardiac function in diabetic ApoEknockout mice.

Abstract

Rutin, a natural bioflavonoid, has demonstrated anti-diabetic and anti-oxidative bioactivity. Oxidative stress is a potential therapeutic target for diabetic cardiomyopathy. We investigated whether rutinadministration (60mg/kg body weight) reduces diabetic cardiomyopathy in a diabetic ApoE knock out mouse model. Diabetes was induced in ApoEknockout mice (male, C57BL/6 background) with a high fat diet combined with injection of streptozotocin. Cardiac function was evaluated by echocardiography and cardiac catheter hemodynamic analysis. Cardiac myocardial hypertrophy, myocardial fibrosis, lipid content, myocardial capillary density, and oxidative stress were detected by a series of histopathological analyses, western blotting, and reactive oxygen species analysis. Diabetic mice showed myocardial hypertrophy, lipid accumulation, myocardial fibrosis, elevated collagen content, deteriorating oxidative stress, and left ventricular systolic and diastolic dysfunction. Rutin reversed the myocardial hypertrophy, alleviated extracellular collagen deposition, and lipid accumulation, but increased capillary density in diabetic myocardial tissues. Moreover, rutin substantially improved cardiac function while decreasing blood glucose and lipid content. Therapeutic rutin administration reduced cardiac remodeling and improved myocardial function in diabetic mice, at least in part by reducing oxidative damage and ectopic lipid deposition, inhibiting fibrosis, and promoting angiogenesis. Thus, rutin may represent a potential therapeutic agent for diabetic cardiomyopathy.

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  • Authors+Show Affiliations

    ,

    Department of Cardiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China; Department of Geriatric Medicine, Lai Wu City People's Hospital, Laiwu, Shandong 271100, China.

    ,

    Laiwu Municipal Center for Disease Control and Prevention, Laiwu, Shandong 271100, China.

    ,

    Department of Geriatric Medicine, Lai Wu City People's Hospital, Laiwu, Shandong 271100, China.

    ,

    Department of Geriatric Medicine, Lai Wu City People's Hospital, Laiwu, Shandong 271100, China.

    ,

    Department of Geriatric Medicine, Lai Wu City People's Hospital, Laiwu, Shandong 271100, China.

    Department of Cardiology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China. Electronic address: sdqdanyi@163.com.

    Source

    European journal of pharmacology 814: 2017 Nov 05 pg 151-160

    MeSH

    Animals
    Apolipoproteins E
    Apoptosis
    Blood Glucose
    Capillaries
    Cholesterol, LDL
    Diabetic Cardiomyopathies
    Disease Progression
    Fibrosis
    Gene Knockout Techniques
    Heart
    Hypertrophy
    Insulin Resistance
    MAP Kinase Signaling System
    Male
    Mice
    Mice, Inbred C57BL
    Myocardium
    Oxidative Stress
    Proto-Oncogene Proteins c-akt
    Rutin
    Triglycerides
    Ventricular Dysfunction, Left
    Ventricular Remodeling

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28826911

    Citation

    Huang, Ruo, et al. "Rutin Alleviates Diabetic Cardiomyopathy and Improves Cardiac Function in Diabetic ApoEknockout Mice." European Journal of Pharmacology, vol. 814, 2017, pp. 151-160.
    Huang R, Shi Z, Chen L, et al. Rutin alleviates diabetic cardiomyopathy and improves cardiac function in diabetic ApoEknockout mice. Eur J Pharmacol. 2017;814:151-160.
    Huang, R., Shi, Z., Chen, L., Zhang, Y., Li, J., & An, Y. (2017). Rutin alleviates diabetic cardiomyopathy and improves cardiac function in diabetic ApoEknockout mice. European Journal of Pharmacology, 814, pp. 151-160. doi:10.1016/j.ejphar.2017.08.023.
    Huang R, et al. Rutin Alleviates Diabetic Cardiomyopathy and Improves Cardiac Function in Diabetic ApoEknockout Mice. Eur J Pharmacol. 2017 Nov 5;814:151-160. PubMed PMID: 28826911.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Rutin alleviates diabetic cardiomyopathy and improves cardiac function in diabetic ApoEknockout mice. AU - Huang,Ruo, AU - Shi,Zhendong, AU - Chen,Li, AU - Zhang,Yanqun, AU - Li,Jing, AU - An,Yi, Y1 - 2017/08/19/ PY - 2017/04/05/received PY - 2017/08/16/revised PY - 2017/08/18/accepted PY - 2017/8/23/pubmed PY - 2018/6/2/medline PY - 2017/8/23/entrez KW - Cardiomyopathy KW - Diabetes KW - Myocardial dysfunction KW - Oxidative stress KW - Rutin SP - 151 EP - 160 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 814 N2 - Rutin, a natural bioflavonoid, has demonstrated anti-diabetic and anti-oxidative bioactivity. Oxidative stress is a potential therapeutic target for diabetic cardiomyopathy. We investigated whether rutinadministration (60mg/kg body weight) reduces diabetic cardiomyopathy in a diabetic ApoE knock out mouse model. Diabetes was induced in ApoEknockout mice (male, C57BL/6 background) with a high fat diet combined with injection of streptozotocin. Cardiac function was evaluated by echocardiography and cardiac catheter hemodynamic analysis. Cardiac myocardial hypertrophy, myocardial fibrosis, lipid content, myocardial capillary density, and oxidative stress were detected by a series of histopathological analyses, western blotting, and reactive oxygen species analysis. Diabetic mice showed myocardial hypertrophy, lipid accumulation, myocardial fibrosis, elevated collagen content, deteriorating oxidative stress, and left ventricular systolic and diastolic dysfunction. Rutin reversed the myocardial hypertrophy, alleviated extracellular collagen deposition, and lipid accumulation, but increased capillary density in diabetic myocardial tissues. Moreover, rutin substantially improved cardiac function while decreasing blood glucose and lipid content. Therapeutic rutin administration reduced cardiac remodeling and improved myocardial function in diabetic mice, at least in part by reducing oxidative damage and ectopic lipid deposition, inhibiting fibrosis, and promoting angiogenesis. Thus, rutin may represent a potential therapeutic agent for diabetic cardiomyopathy. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/28826911/Rutin_alleviates_diabetic_cardiomyopathy_and_improves_cardiac_function_in_diabetic_ApoEknockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(17)30538-1 DB - PRIME DP - Unbound Medicine ER -