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Attenuation of diabetic cardiomyopathy by relying on kirenol to suppress inflammation in a diabetic rat model.
J Cell Mol Med. 2019 11; 23(11):7651-7663.JC

Abstract

Diabetic cardiomyopathy is characterized by diabetes-induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation-related signalling pathways. Kirenol, isolated from Herba Siegesbeckiae, has potent anti-inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose-induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis-related protein expression. Kirenol gavage could affect the expression of pro-inflammatory cytokines in a dose-dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high-dose kirenol-treated group at some time-points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen-activated protein kinase subfamily and nuclear translocation of NF-κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis-related and apoptosis-related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF-κB, Smad3/4, SP1 and AP-1 in the nucleus of diabetic myocardium were significantly down-regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis-related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles.

Authors+Show Affiliations

Laboratory of Platelet and Endothelium Biology, Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China. Department of Physiology and Pharmacology, Medical College, Hubei University of Arts and Science, Xiangyang, China.Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.Department of Cardiology, the Third Xiangya Hospital, Central South University, Changsha, China.Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Laboratory of Platelet and Endothelium Biology, Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Pharmacy, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Immunology, Medical College, Hubei University of Arts and Science, Xiangyang, China.Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.Laboratory of Platelet and Endothelium Biology, Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pub Type(s)

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

Language

eng

PubMed ID

31565849

Citation

Wu, Bin, et al. "Attenuation of Diabetic Cardiomyopathy By Relying On Kirenol to Suppress Inflammation in a Diabetic Rat Model." Journal of Cellular and Molecular Medicine, vol. 23, no. 11, 2019, pp. 7651-7663.
Wu B, Huang XY, Li L, et al. Attenuation of diabetic cardiomyopathy by relying on kirenol to suppress inflammation in a diabetic rat model. J Cell Mol Med. 2019;23(11):7651-7663.
Wu, B., Huang, X. Y., Li, L., Fan, X. H., Li, P. C., Huang, C. Q., Xiao, J., Gui, R., & Wang, S. (2019). Attenuation of diabetic cardiomyopathy by relying on kirenol to suppress inflammation in a diabetic rat model. Journal of Cellular and Molecular Medicine, 23(11), 7651-7663. https://doi.org/10.1111/jcmm.14638
Wu B, et al. Attenuation of Diabetic Cardiomyopathy By Relying On Kirenol to Suppress Inflammation in a Diabetic Rat Model. J Cell Mol Med. 2019;23(11):7651-7663. PubMed PMID: 31565849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Attenuation of diabetic cardiomyopathy by relying on kirenol to suppress inflammation in a diabetic rat model. AU - Wu,Bin, AU - Huang,Xue-Yuan, AU - Li,Le, AU - Fan,Xiao-Hang, AU - Li,Peng-Cheng, AU - Huang,Chuan-Qi, AU - Xiao,Juan, AU - Gui,Rong, AU - Wang,Shun, Y1 - 2019/09/29/ PY - 2019/03/24/received PY - 2019/06/23/revised PY - 2019/07/23/accepted PY - 2019/10/1/pubmed PY - 2020/9/10/medline PY - 2019/10/1/entrez KW - cardiac dysfunction KW - diabetic cardiomyopathy KW - fibrosis KW - inflammation KW - myocardial remodelling SP - 7651 EP - 7663 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 23 IS - 11 N2 - Diabetic cardiomyopathy is characterized by diabetes-induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation-related signalling pathways. Kirenol, isolated from Herba Siegesbeckiae, has potent anti-inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose-induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis-related protein expression. Kirenol gavage could affect the expression of pro-inflammatory cytokines in a dose-dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high-dose kirenol-treated group at some time-points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen-activated protein kinase subfamily and nuclear translocation of NF-κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis-related and apoptosis-related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF-κB, Smad3/4, SP1 and AP-1 in the nucleus of diabetic myocardium were significantly down-regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis-related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/31565849/Attenuation_of_diabetic_cardiomyopathy_by_relying_on_kirenol_to_suppress_inflammation_in_a_diabetic_rat_model_ L2 - https://doi.org/10.1111/jcmm.14638 DB - PRIME DP - Unbound Medicine ER -