Curcumin analogue C66 attenuates obesity-induced myocardial injury by inhibiting JNK-mediated inflammation.

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.

• Authors: Lin Ye, Xiaojun Chen, Minxiu Wang, Leiming Jin, Zaishou Zhuang, Daona Yang, Xinfu Guan, Aleksandr V Samorodov, Valentin N Pavlov, Nipon Chattipakorn, Jianpeng Feng, Yi Wang, Wu Luo, Guang Liang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 143 Pg. 112121 (Nov 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34474346 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• 2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone
• Anti-Inflammatory Agents
• Benzylidene Compounds
• Cyclohexanones
• Cytokines
• NF-kappa B
• Palmitic Acid
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Benzylidene Compounds (pharmacology)
• Cardiomyopathies (enzymology, etiology, pathology, prevention & control)
• Cell Line
• Cyclohexanones (pharmacology)
• Cytokines (metabolism)
• Diet, High-Fat
• Disease Models, Animal
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Male
• Mice, Inbred C57BL
• Myocarditis (enzymology, etiology, pathology, prevention & control)
• Myocytes, Cardiac (drug effects, enzymology, pathology)
• NF-kappa B (metabolism)
• Obesity (complications)
• Palmitic Acid (toxicity)
• Rats
• Signal Transduction
• Mice