title: Inhibition of inflammation and oxidative stress by an imidazopyridine derivative X22 prevents heart injury from obesity.
abstract: 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-κB) 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-κB may be important therapeutic targets for obesity-related complications.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.|Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Kesong
authors.initials: K
authors.lastname: Peng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Kongqin
authors.initials: K
authors.lastname: Lu
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Gaozhi
authors.initials: G
authors.lastname: Chen
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D059305:Diet, High-Fat; D005355:Fibrosis; D006335:Heart Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D019308:Palmitic Acid; D011725:Pyridines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007093:Imidazoles; D008055:Lipids; D016328:NF-kappa B; D011725:Pyridines; D017382:Reactive Oxygen Species; C000600451:X22 compound; D019308:Palmitic Acid
keywords: imidazopyridine derivative; inflammation; obesity-related cardiomyopathy; oxidative stress