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: Weixin Li, Lintao Wang, Weijian Huang, Melissa Skibba, Qilu Fang, Longteng Xie, Tiemin Wei, Zhiguo Feng, Guang Liang
• Journal: Vascular pharmacology (Vascul Pharmacol) Vol. 72 Pg. 153-62 (Sep 2015) ISSN: 1879-3649 [Electronic] United States
• PMID: 25989105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• NF-E2-Related Factor 2
• NF-kappa B
• Palmitates
• Reactive Oxygen Species

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Arteries (drug effects, metabolism)
• Diet, High-Fat
• Fibrosis (drug therapy, metabolism)
• Inflammation (drug therapy, metabolism)
• Macrophages (drug effects, metabolism)
• Male
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Obesity (drug therapy, metabolism)
• Oxidative Stress (drug effects)
• Palmitates (pharmacology)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)