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5-甲氧基黄酮通过靶向CYP1A1改善非酒精性脂肪性肝病的作用机制研究

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

Journal:FREE RADICAL BIOLOGY AND MEDICINE

IF:8.1

DOI:10.1016/j.freeradbiomed.2022.12.093

PMID:36587922

Published:2022-12-30

research field:分子生物学药理学代谢紊乱肝病学

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.

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