Cardioprotective effects of the novel curcumin analogue C66 in diabetic mice is dependent on JNK2 inactivation.

Abstract

AIM:

Diabetic cardiomyopathy is an independent cardiac injury that can develop in diabetic individuals. Our previous study showed that C66, a curcumin analogue, protects against diabetes-induced cardiac damage. The present study sought to reveal the underlying mechanisms of C66-mediated cardioprotection.

METHODS:

An experimental diabetic model was established using JNK2-/- and wild-type (WT) mice. C66 (5 mg/kg) was administered orally every other day for 3 months. Body weight, plasma glucose levels, cardiac function, and structure were measured. Masson trichrome and TUNEL staining were used to assess myocardial fibrosis and apoptosis, respectively. mRNA and protein levels of inflammation, fibrosis, oxidative stress, and apoptosis molecules were measured by quantitative PCR and Western blot, respectively.

RESULTS:

Neither C66 treatment nor JNK2 knockout affected body weight or plasma glucose levels. Cardiac inflammation, fibrosis, oxidative stress, and apoptosis were increased in WT diabetic compared to WT control mice, all of which were attenuated by C66 treatment. However, these pathological and molecular changes induced by diabetes were eliminated in JNK2-/- diabetic mice compared to JNK2-/- control mice, and C66 treatment did not further affect these parameters in JNK2-/- diabetic mice.

CONCLUSIONS:

Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK2 relative pathways.

• Authors: Cheng Li, Xiao Miao, Yan Lou, Zhengyang Lu, Binay Kumar Adhikari, Yangwei Wang, Quan Liu, Jian Sun, Yonggang Wang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 22 Issue 12 Pg. 6314-6326 (12 2018) ISSN: 1582-4934 [Electronic] England
• PMID: 30320490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Mitogen-Activated Protein Kinase 9
• Curcumin

Topics

• Animals
• Apoptosis (drug effects)
• Curcumin (administration & dosage, analogs & derivatives)
• Diabetes Mellitus, Experimental (drug therapy, genetics, pathology)
• Diabetic Cardiomyopathies (drug therapy, genetics, pathology)
• Diabetic Nephropathies (drug therapy, genetics, pathology)
• Fibrosis (drug therapy, genetics, pathology)
• Humans
• Inflammation (drug therapy, genetics, pathology)
• Mice
• Mice, Inbred NOD
• Mitogen-Activated Protein Kinase 9 (genetics)
• Oxidative Stress (drug effects)
• Phosphorylation