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

Yurou Zhang; Qinghua Fu; Tian Wu; Kang Liu; Yang Xiao; Qichao Liao; Xinyi Qi; Yixing Li; Lei Zhou

doi:10.1016/j.freeradbiomed.2022.12.093

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

Free Radic Biol Med. 2023 Feb 1:195:178-191. doi: 10.1016/j.freeradbiomed.2022.12.093. Epub 2022 Dec 30.

Authors

Yurou Zhang¹, Qinghua Fu¹, Tian Wu¹, Kang Liu¹, Yang Xiao¹, Qichao Liao¹, Xinyi Qi¹, Yixing Li¹, Lei Zhou²

Affiliations

¹ State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, 530004, China.
² State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, 530004, China. Electronic address: zhoulei@gxu.edu.cn.

PMID: 36587922
DOI: 10.1016/j.freeradbiomed.2022.12.093

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.

Keywords: 5-Methoxyflavone; Cytochrome P450 1A1; NAFLD; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

5-methoxyflavone
Cytochrome P-450 CYP1A1