1. Curcumin analogue C66 attenuates obesity-induced myocardial injury by inhibiting JNK-mediated inflammation.
- Author
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Ye L, Chen X, Wang M, Jin L, Zhuang Z, Yang D, Guan X, Samorodov AV, Pavlov VN, Chattipakorn N, Feng J, Wang Y, Luo W, and Liang G
- Subjects
- Animals, Cardiomyopathies enzymology, Cardiomyopathies etiology, Cardiomyopathies pathology, Cell Line, Cytokines metabolism, Diet, High-Fat, Disease Models, Animal, Male, Mice, Inbred C57BL, Myocarditis enzymology, Myocarditis etiology, Myocarditis pathology, Myocytes, Cardiac enzymology, Myocytes, Cardiac pathology, NF-kappa B metabolism, Palmitic Acid toxicity, Rats, Signal Transduction, Mice, Anti-Inflammatory Agents pharmacology, Apoptosis drug effects, Benzylidene Compounds pharmacology, Cardiomyopathies prevention & control, Cyclohexanones pharmacology, JNK Mitogen-Activated Protein Kinases metabolism, Myocarditis prevention & control, Myocytes, Cardiac drug effects, Obesity complications
- Abstract
Obesity has been recognized as a major risk factor for the development of chronic cardiomyopathy, which is associated with increased cardiac inflammation, fibrosis, and apoptosis. We previously developed an anti-inflammatory compound C66, which prevented inflammatory diabetic complications via targeting JNK. In the present study, we have tested the hypothesis that C66 could prevent obesity-induced cardiomyopathy by suppressing JNK-mediated inflammation. High-fat diet (HFD)-induced obesity mouse model and palmitic acid (PA)-challenged H9c2 cells were used to develop inflammatory cardiomyopathy and evaluate the protective effects of C66. Our data demonstrate a protective effect of C66 against obesity-induced cardiac inflammation, cardiac hypertrophy, fibrosis, and dysfunction, overall providing cardio-protection. C66 administration attenuates HFD-induced myocardial inflammation by inhibiting NF-κB and JNK activation in mouse hearts. In vitro, C66 prevents PA-induced myocardial injury and apoptosis in H9c2 cells, accompanied with inhibition against PA-induced JNK/NF-κB activation and inflammation. The protective effect of C66 is attributed to its potential to inhibit JNK activation, which led to reduced pro-inflammatory cytokine production and reduced apoptosis in cardiomyocytes both in vitro and in vivo. In summary, C66 provides significant protection against obesity-induced cardiac dysfunction, mainly by inhibiting JNK activation and JNK-mediated inflammation. Our data indicate that inhibition of JNK is able to provide significant protection against obesity-induced cardiac dysfunction., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2021
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