6-Methyl flavone inhibits Nogo-B expression and improves high fructose diet-induced liver injury in mice.
Acta Pharmacol Sin
; 44(11): 2216-2229, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37402997
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome Metabólico
/
Flavonas
/
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas
/
Enfermedad del Hígado Graso no Alcohólico
Límite:
Animals
Idioma:
En
Revista:
Acta Pharmacol Sin
Asunto de la revista:
FARMACOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China