Alpha-naphthoflavone attenuates non-alcoholic fatty liver disease in oleic acid-treated HepG2 hepatocytes and in high fat diet-fed mice.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease. The literature suggests that the aryl hydrocarbon receptor (AHR) may be a key player in the pathogenesis of NAFLD, and it can modulate the synthesis of cytochrome P450 1A1 (CYP1A1) and tumor necrosis factor-α (TNF-α). Previous studies have shown that CYP1A1 is a key enzyme of oxidative stress, TNF-α is involved in the formation of insulin resistance (IR), oxidative stress and insulin resistance are the key factors for the formation of NAFLD. Therefore, it can be said that AHR may participate in contributing to NAFLD by regulating CYP1A1 and TNF-α. Alpha-naphthoflavone (ANF) is an effective AHR inhibitor. The present study was designed to explore the hepatoprotective effect of ANF in high fat diet (HFD)-induced NAFLD mice and oleic acid (OA)-treated HepG2 hepatocytes. Mice were fed HFD to induce NAFLD, HepG2 cells were exposed to OA to induce hepatocyte injury, and ANF significantly reduced mouse and cellular liver damage compared to the HFD-induced NAFLD and OA-treated HepG2 hepatocytes. ANF treatment reduces liver damage by reducing ROS and IR, the data show that ANF inhibits the expression of AHR, CYP1A1 and TNF-α in NAFLD. Taken together, these findings show that ANF alleviate NAFLD via regulation of AHR/CYP1A1 and AHR/TNF-α pathways, which may have potential for further development as novel therapeutic agents for NAFLD.

• Authors: Hongguang Xia, Xiangyu Zhu, Xiaoyan Zhang, Haiyan Jiang, Biao Li, Zhihao Wang, Dalang Li, Yong Jin
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 118 Pg. 109287 (Oct 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 31401392 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Benzoflavones
• Oleic Acid
• Malondialdehyde
• alpha-naphthoflavone
• Glycogen
• Catalase
• Superoxide Dismutase

Topics

• Animals
• Benzoflavones (pharmacology, therapeutic use)
• Catalase (metabolism)
• Cell Proliferation (drug effects)
• Diet, High-Fat
• Glycogen (metabolism)
• Hep G2 Cells
• Hepatocytes (drug effects, pathology)
• Humans
• Insulin Resistance
• Lipid Droplets (drug effects, metabolism)
• Lipid Metabolism (drug effects)
• Liver (drug effects, pathology)
• Male
• Malondialdehyde (metabolism)
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (drug therapy, pathology)
• Oleic Acid
• Oxidative Stress (drug effects)
• Superoxide Dismutase (metabolism)