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An Aza resveratrol-chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress.
J Cell Mol Med. 2018 03; 22(3):1931-1943.JC

Abstract

Inflammation and oxidative stress play a crucial role in the development of diabetic cardiomyopathy (DCM). We previously had synthesized an Aza resveratrol-chalcone derivative 6b, of which effectively suppressing lipopolysaccharide (LPS)-induced inflammatory response in macrophages. This study aimed to investigate the potential protective effect of 6b on DCM and underlying mechanism. In H9c2 myocardial cells, 6b potently decreased high glucose (HG)-induced cell fibrosis, hypertrophy and apoptosis, alleviating inflammatory response and oxidant stress. In STZ-induced type 1 diabetic mice (STZ-DM1), orally administration with 6b for 16 weeks significantly attenuated cardiac hypertrophy, apoptosis and fibrosis. The expression of inflammatory cytokines and oxidative stress biomarkers was also suppressed by 6b distinctly, without affecting blood glucose and body weight. The anti-inflammatory and antioxidative activities of 6b were mechanistic associated with nuclear factor-kappa B (NF-κB) nucleus entry blockage and Nrf2 activation both in vitro and in vivo. The results indicated that 6b can be a promising cardioprotective agent in treatment of DCM via inhibiting inflammation and alleviating oxidative stress. This study also validated the important role of NF-κB and Nrf2 taken in the pathogenesis of DCM, which could be therapeutic targets for diabetic comorbidities.

Authors+Show Affiliations

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Translational Medicine Center in Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Translational Medicine Center in Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Endocrinology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Translational Medicine Center in Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Pub Type(s)

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

Language

eng

PubMed ID

29327811

Citation

You, Shengban, et al. "An Aza Resveratrol-chalcone Derivative 6b Protects Mice Against Diabetic Cardiomyopathy By Alleviating Inflammation and Oxidative Stress." Journal of Cellular and Molecular Medicine, vol. 22, no. 3, 2018, pp. 1931-1943.
You S, Qian J, Sun C, et al. An Aza resveratrol-chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress. J Cell Mol Med. 2018;22(3):1931-1943.
You, S., Qian, J., Sun, C., Zhang, H., Ye, S., Chen, T., Xu, Z., Wang, J., Huang, W., & Liang, G. (2018). An Aza resveratrol-chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress. Journal of Cellular and Molecular Medicine, 22(3), 1931-1943. https://doi.org/10.1111/jcmm.13477
You S, et al. An Aza Resveratrol-chalcone Derivative 6b Protects Mice Against Diabetic Cardiomyopathy By Alleviating Inflammation and Oxidative Stress. J Cell Mol Med. 2018;22(3):1931-1943. PubMed PMID: 29327811.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An Aza resveratrol-chalcone derivative 6b protects mice against diabetic cardiomyopathy by alleviating inflammation and oxidative stress. AU - You,Shengban, AU - Qian,Jianchang, AU - Sun,Chuchu, AU - Zhang,Hailing, AU - Ye,Shiju, AU - Chen,Taiwei, AU - Xu,Zheng, AU - Wang,Jingying, AU - Huang,Weijian, AU - Liang,Guang, Y1 - 2018/01/12/ PY - 2017/08/21/received PY - 2017/10/04/accepted PY - 2018/1/13/pubmed PY - 2019/10/16/medline PY - 2018/1/13/entrez KW - NF-κB KW - Nrf2 KW - diabetic cardiomyopathy KW - inflammation KW - oxidative stress SP - 1931 EP - 1943 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 22 IS - 3 N2 - Inflammation and oxidative stress play a crucial role in the development of diabetic cardiomyopathy (DCM). We previously had synthesized an Aza resveratrol-chalcone derivative 6b, of which effectively suppressing lipopolysaccharide (LPS)-induced inflammatory response in macrophages. This study aimed to investigate the potential protective effect of 6b on DCM and underlying mechanism. In H9c2 myocardial cells, 6b potently decreased high glucose (HG)-induced cell fibrosis, hypertrophy and apoptosis, alleviating inflammatory response and oxidant stress. In STZ-induced type 1 diabetic mice (STZ-DM1), orally administration with 6b for 16 weeks significantly attenuated cardiac hypertrophy, apoptosis and fibrosis. The expression of inflammatory cytokines and oxidative stress biomarkers was also suppressed by 6b distinctly, without affecting blood glucose and body weight. The anti-inflammatory and antioxidative activities of 6b were mechanistic associated with nuclear factor-kappa B (NF-κB) nucleus entry blockage and Nrf2 activation both in vitro and in vivo. The results indicated that 6b can be a promising cardioprotective agent in treatment of DCM via inhibiting inflammation and alleviating oxidative stress. This study also validated the important role of NF-κB and Nrf2 taken in the pathogenesis of DCM, which could be therapeutic targets for diabetic comorbidities. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/29327811/An_Aza_resveratrol_chalcone_derivative_6b_protects_mice_against_diabetic_cardiomyopathy_by_alleviating_inflammation_and_oxidative_stress_ L2 - https://doi.org/10.1111/jcmm.13477 DB - PRIME DP - Unbound Medicine ER -