Attenuation of diabetic cardiomyopathy by relying on kirenol to suppress inflammation in a diabetic rat model
Bin Wu
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
Search for more papers by this authorXue-Yuan Huang
Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorLe Li
Department of Cardiology, the Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorXiao-Hang Fan
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorPeng-Cheng Li
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
Search for more papers by this authorChuan-Qi Huang
Department of Pharmacy, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorJuan Xiao
Department of Immunology, Medical College, Hubei University of Arts and Science, Xiangyang, China
Search for more papers by this authorCorresponding Author
Rong Gui
Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China
Correspondence
Shun Wang, 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.
Email: [email protected]
Rong Gui, Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shun Wang
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
Correspondence
Shun Wang, 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.
Email: [email protected]
Rong Gui, Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Email: [email protected]
Search for more papers by this authorBin Wu
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
Search for more papers by this authorXue-Yuan Huang
Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorLe Li
Department of Cardiology, the Third Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorXiao-Hang Fan
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorPeng-Cheng Li
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
Search for more papers by this authorChuan-Qi Huang
Department of Pharmacy, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Search for more papers by this authorJuan Xiao
Department of Immunology, Medical College, Hubei University of Arts and Science, Xiangyang, China
Search for more papers by this authorCorresponding Author
Rong Gui
Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China
Correspondence
Shun Wang, 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.
Email: [email protected]
Rong Gui, Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Shun Wang
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
Correspondence
Shun Wang, 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.
Email: [email protected]
Rong Gui, Department of Transfusion Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Email: [email protected]
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare.
Open Research
DATA AVAILABILITY STATEMENT
All data generated or analysed during this study are included in this article.
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