Xuemei Chen1, Jianchang Qian1, Lintao Wang1, Jieli Li1, Yunjie Zhao1, Jibo Han1,2, Zia Khan3, Xiaojun Chen1, Jingying Wang4, Guang Liang5. 1. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. 2. Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. 3. Department of Pathology and Laboratory Medicine, Western University, London, ON, N6A5C1, Canada. 4. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. jingyingwang0605@163.com. 5. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China. wzmcliangguang@163.com.
Abstract
PURPOSE: Suppression of inflammation and oxidative stress is an attractive strategy to against diabetic cardiomyopathy (DCM). Kaempferol (KPF) exerts both anti-inflammatory and antioxidant pharmacological properties. However, little is known about the effect of KPF on protecting myocardial injury in diabetes. The present study aimed to investigate the effect of KPF on DCM and underlying mechanism. METHODS: Anti-inflammation and anti-oxidative stress activities of KPF were evaluated in H9c2 cells or primary cardiomyocytes by real-time quantitate PCR, immunoblotting, immunofluorescence, ELISA, and FACS. Streptozotocin (STZ)-induced type 1 diabetes mellitus mice were constructed. Corresponding to experiments in vitro, the therapeutic effect of KPF was also assessed using heart tissues from mice. RESULTS: KPF significantly inhibited high glocose (HG) induced expression of inflammatory cytokines and generation of ROS, leading to reduced fibrotic responses and cell apoptosis in vitro. KPF mediated DCM protective effects through inhibiting nuclear factor-κB (NF-κB) nucleus translocation and activating nuclear factor-erythroid 2 p45-related factor-2 (Nrf-2). In STZ-induced type 1 diabetic mouse model, KPF prevented diabetes-induced cardiac fibrosis and apoptosis. These changes were also accompanied by reducing inflammation and oxidative stress in diabetic mice hearts. CONCLUSION: KPF is a potential therapeutic agent for the treatment of DCM, mechanically linked to inhibition of NF-κB and Nrf-2 activation.
PURPOSE: Suppression of inflammation and oxidative stress is an attractive strategy to against diabetic cardiomyopathy (DCM). Kaempferol (KPF) exerts both anti-inflammatory and antioxidant pharmacological properties. However, little is known about the effect of KPF on protecting myocardial injury in diabetes. The present study aimed to investigate the effect of KPF on DCM and underlying mechanism. METHODS: Anti-inflammation and anti-oxidative stress activities of KPF were evaluated in H9c2 cells or primary cardiomyocytes by real-time quantitate PCR, immunoblotting, immunofluorescence, ELISA, and FACS. Streptozotocin (STZ)-induced type 1 diabetes mellitusmice were constructed. Corresponding to experiments in vitro, the therapeutic effect of KPF was also assessed using heart tissues from mice. RESULTS:KPF significantly inhibited high glocose (HG) induced expression of inflammatory cytokines and generation of ROS, leading to reduced fibrotic responses and cell apoptosis in vitro. KPF mediated DCM protective effects through inhibiting nuclear factor-κB (NF-κB) nucleus translocation and activating nuclear factor-erythroid 2 p45-related factor-2 (Nrf-2). In STZ-induced type 1 diabeticmouse model, KPF prevented diabetes-induced cardiac fibrosis and apoptosis. These changes were also accompanied by reducing inflammation and oxidative stress in diabeticmice hearts. CONCLUSION:KPF is a potential therapeutic agent for the treatment of DCM, mechanically linked to inhibition of NF-κB and Nrf-2 activation.