A Newly Designed Curcumin Analog Y20 Mitigates Cardiac Injury via Anti-Inflammatory and Anti-Oxidant Actions in Obese Rats |
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Authors: | Yuanyuan Qian Peng Zhong Dandan Liang Zheng Xu Melissa Skibba Chunlai Zeng Xiaokun Li Tiemin Wei Lianpin Wu Guang Liang |
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Affiliation: | 1. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.; 2. Department of Cardiology, the 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.; 3. Department of Cardiology, the 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.; National Institutes of Health, UNITED STATES, |
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Abstract: | Obesity is strongly associated with the cause of structural and functional changes of the heart in both human and animal models. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiac disorders. Curcumin is a natural product from Curcuma Longa with multiple bioactivities. In our previous study, in order to reach better anti-inflammatory and anti-oxidant dual activities, we designed a new mono-carbonyl curcumin analog, Y20, via the structural modification with both trifluoromethyl and bromine. This study was designed to investigate the protective effects of Y20 on obesity-induced cardiac injury and its underlying mechanisms. In high fat diet–fed rats, oral administration of Y20 at 20 mg/kg or curcumin at 50 mg/kg significantly decreased the cardiac inflammation and oxidative stress and eventually improved the cardiac remodeling by mitigating cardiac disorganization, hypertrophy, fibrosis and apoptosis. Y20 at 20 mg/kg showed comparable and even stronger bioactivities than curcumin at 50 mg/kg. The beneficial actions of Y20 are closely associated with its ability to increase Nrf2 expression and inhibit NF-κB activation. Taken together, these results suggest that Y20 may have a great therapeutic potential in the treatment of obesity-induced cardiac injury using Nrf2 and NF-κB as the therapeutic targets for treating obesity-related disorders. |
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