5-Methoxyflavone ameliorates non-alcoholic fatty liver disease through targeting the cytochrome P450 1A1.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease that is closely related to obesity and metabolic disorders. 5-methoxyflavone (5-MF) is a flavonoid with DNA polymerase-β inhibitory properties. In this study, we explored the effects of 5-MF on NAFLD and its potential mechanisms using oleic acid/palmitic acid-treated HepG2 cells and high-fat diet-fed C57BL/6J mice. Our results showed that 5-MF not only alleviated fat deposition and hepatic steatosis, but also improved oxidative damage. In addition, 5-MF has the effect of alleviating disorders of glucose metabolism and enhancing energy expenditure in HFD-induced obese mice. Mechanistically, reverse screening methods and molecular docking analysis were used in combination, and revealed that cytochrome P450 1A1 (CYP1A1) is the target for 5-MF. Further experiments showed that 5-MF ameliorated triglycerides deposition by inhibiting the enzyme activity and protein expression of CYP1A1. In conclusion, 5-MF provides a novel strategy for the prevention and treatment of high-fat-induced NAFLD.

• Authors: Yurou Zhang, Qinghua Fu, Tian Wu, Kang Liu, Yang Xiao, Qichao Liao, Xinyi Qi, Yixing Li, Lei Zhou
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 195 Pg. 178-191 (02 01 2023) ISSN: 1873-4596 [Electronic] United States
• PMID: 36587922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• 5-methoxyflavone
• Cytochrome P-450 CYP1A1

Topics

• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (metabolism)
• Liver (metabolism)
• Cytochrome P-450 CYP1A1 (genetics)
• Molecular Docking Simulation
• Mice, Inbred C57BL
• Diet, High-Fat (adverse effects)
• Lipid Metabolism