@article{APS10918,
author = {Ke Gong and Zhen Zhang and Sha-sha Chen and Xin-ran Zhu and Meng-yao Wang and Xin-yue Yang and Chen Ding and Ji-hong Han and Qing-shan Li and Ya-jun Duan},
title = {6-Methyl flavone inhibits Nogo-B expression and improves high fructose diet-induced liver injury in mice},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {11},
year = {2023},
keywords = {},
abstract = {Excessive fructose consumption increases hepatic de novo lipogenesis, resulting in cellular stress, inflammation and liver injury. Nogo-B is a resident protein of the endoplasmic reticulum that regulates its structure and function. Hepatic Nogo-B is a key protein in glycolipid metabolism, and inhibition of Nogo-B has protective effects against metabolic syndrome, thus small molecules that inhibit Nogo-B have therapeutic benefits for glycolipid metabolism disorders. In this study we tested 14 flavones/isoflavones in hepatocytes using dual luciferase reporter system based on the Nogo-B transcriptional response system, and found that 6-methyl flavone (6-MF) exerted the strongest inhibition on Nogo-B expression in hepatocytes with an IC50 value of 15.85 μM. Administration of 6-MF (50 mg· kg−1 ·d−1, i.g. for 3 weeks) significantly improved insulin resistance along with ameliorated liver injury and hypertriglyceridemia in high fructose diet-fed mice. In HepG2 cells cultured in a media containing an FA-fructose mixture, 6-MF (15 μM) significantly inhibited lipid synthesis, oxidative stress and inflammatory responses. Furthermore, we revealed that 6-MF inhibited Nogo-B/ChREBP-mediated fatty acid synthesis and reduced lipid accumulation in hepatocytes by restoring cellular autophagy and promoting fatty acid oxidation via the AMPKα-mTOR pathway. Thus, 6-MF may serve as a potential Nogo-B inhibitor to treat metabolic syndrome caused by glycolipid metabolism dysregulation.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10918}
}