title: Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate high fat diet-induced arterial injuries.
abstract: Obesity is strongly associated with the cause of structural and functional changes of the artery. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiovascular disorders. Our group previously found that an imidazopyridine derivative X22 showed excellent anti-inflammatory activity in LPS-stimulated macrophages. This study was designed to investigate the protective effects of X22 on high fat diet (HFD)-induced arterial injury and its underlying mechanisms. We observed that palmitate (PA) treatment in HUVECs induced a marked increase in reactive oxygen species, inflammation, apoptosis, and fibrosis. All of these changes were effectively suppressed by X22 treatment in a dose-dependent manner, associated with NF-κB inactivation and Nrf-2 activation. In HFD-fed rats, administration of X22 at 10mg/kg significantly decreased the arterial inflammation and oxidative stress, and eventually improved the arterial matrix remodeling and apoptosis. X22 at 10mg/kg showed a comparable bioactivity with the positive control, curcumin at 50mg/kg. The in vivo beneficial effects of X22 are also associated with its ability to increase Nrf2 expression and inhibit NF-κB activation in the artery of HFD-fed rats. Overall, these results suggest that X22 may have therapeutic potential in the treatment of obesity-induced artery injury via regulation of Nrf2-mediated oxidative stress and NF-κB-mediated inflammation.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Cardiology, the Fifth Affiliated Hospital, Wenzhou Medical University, Lishui, Zhejiang, China.
authors.forename: Weixin
authors.initials: W
authors.lastname: Li
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Melissa
authors.initials: M
authors.lastname: Skibba
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Qilu
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Infectious Diseases, The Affiliated Xiangshan Hospital, Wenzhou Medical University, Xiangshan, Zhejiang, China.
authors.forename: Longteng
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Cardiology, the Fifth Affiliated Hospital, Wenzhou Medical University, Lishui, Zhejiang, China.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Wei
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Infectious Diseases, The Affiliated Xiangshan Hospital, Wenzhou Medical University, Xiangshan, Zhejiang, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: wzmcliangguang@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D010168:Palmitates; D017382:Reactive Oxygen Species
keywords: Free fatty acids; Inflammation; Oxidative stress; Vascular injury; Vasoprotection