Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 20, Issue 8, Pages 1427-1442Publisher
WILEY
DOI: 10.1111/jcmm.12832
Keywords
obesity-related cardiomyopathy; imidazopyridine derivative; oxidative stress; inflammation
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Funding
- Natural Science Funding of China [21272179, 81200572, 81373312]
- High-level Innovative Talent Funding of Zhejiang Department of Health [2010-017]
- Zhejiang Key Group in Scientific Innovation [2010R50042]
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Inflammation and oxidative stress plays an important role in the development of obesity-related complications and cardiovascular disease. Benzimidazole and imidazopyridine compounds are a class of compounds with a variety of activities, including anti-inflammatory, antioxidant and anti-cancer. X22 is an imidazopyridine derivative we synthesized and evaluated previously for anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. However, its ability to alleviate obesity-induced heart injury via its anti-inflammatory actions was unclear. This study was designed to evaluate the cardioprotective effects of X22 using cell culture studies and a high-fat diet rat model. We observed that palmitic acid treatment in cardiac-derived H9c2 cells induced a significant increase in reactive oxygen species, inflammation, apoptosis, fibrosis and hypertrophy. All of these changes were inhibited by treatment with X22. Furthermore, oral administration of X22 suppressed high-fat diet-induced oxidative stress, inflammation, apoptosis, hypertrophy and fibrosis in rat heart tissues and decreased serum lipid concentration. We also found that the anti-inflammatory and anti-oxidative actions of X22 were associated with Nrf2 activation and nuclear factor-kappaB (NF-kappa B) inhibition, respectively, both in vitro and in vivo. The results of this study indicate that X22 may be a promising cardioprotective agent and that Nrf2 and NF-kappa B may be important therapeutic targets for obesity-related complications.
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