Open AccessCardioprotective effects of the novel curcumin analogue C66 in diabetic mice is dependent on JNK 2 inactivation
Author(s) -
Li Cheng,
Miao Xiao,
Lou Yan,
Lu Zhengyang,
Adhikari Binay Kumar,
Wang Yangwei,
Liu Quan,
Sun Jian,
Wang Yonggang
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13924
Subject(s) - diabetic cardiomyopathy , medicine , tunel assay , diabetes mellitus , fibrosis , endocrinology , inflammation , oxidative stress , apoptosis , p38 mitogen activated protein kinases , curcumin , myocardial fibrosis , chemistry , pharmacology , mapk/erk pathway , cardiomyopathy , signal transduction , heart failure , immunohistochemistry , biochemistry
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 JNK 2 −/− 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 JNK 2 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 JNK 2 −/− diabetic mice compared to JNK 2 −/− control mice, and C66 treatment did not further affect these parameters in JNK 2 −/− diabetic mice. Conclusions Our results indicate that C66 ameliorates diabetic cardiomyopathy by inhibiting JNK 2 relative pathways.