An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation.

Abstract

Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload. We utilized palmitic acid (PA) challenging in mouse peritoneal macrophages and apolipoprotein E knockout (ApoE-/-) mice fed a high fat diet (HFD) to study whether L6H21 mitigates the inflammatory response. Our studies show that L6H21 significantly reduced PA-induced expression of inflammatory cytokines in macrophages by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NFκB) signaling pathways. L6H21 also reduced fibrosis in the kidney and heart tissues, and indices of inflammatory response in the ApoE-/- mice fed a HFD. These effects in vivo were also associated with inhibition of MAPK and NFκB signaling by L6H21. These findings strongly suggest that L6H21 may be a potential agent for high fat diet-induced injuries in heart and kidney.

• Authors: Xiong Chen, Weihui Yu, Weixin Li, Hailing Zhang, Weijian Huang, Jingying Wang, Weiwei Zhu, Qilu Fang, Chao Chen, Xiaokun Li, Guang Liang
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 338 Pg. 43-53 (01 01 2018) ISSN: 1096-0333 [Electronic] United States
• PMID: 29128402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Inc.

Chemical References

• 2,3-dimethoxy-4'-ethoxychalcone
• Anti-Inflammatory Agents
• Apolipoproteins E
• Chalcones
• NF-kappa B
• Palmitic Acid

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apolipoproteins E (physiology)
• Chalcones (pharmacology)
• Diet, High-Fat
• Heart (drug effects)
• Hyperlipidemias (complications)
• Kidney (drug effects, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (pathology)
• NF-kappa B (antagonists & inhibitors)
• Palmitic Acid (toxicity)