Four flavonoids from propolis ameliorate free fatty acids-induced non-alcoholic steatohepatitis in HepG2 cells: Involvement of enhanced AMPK activation, mTOR-NF-κBp65 interaction, and PTEN expression. (March 2023)

• Record Type: Journal Article
• Authors: Ye, Manhong; Fan, Shuhang; Li, Xiaoyuan; Yang, Shengmei; Ji, Chao; Ji, Fubiao; Zhou, Bin
• Is Part Of: Journal of functional foods. Volume 102(2023)
• Publication Date: 2023-03
• Subjects: NAFLD nonalcoholic fatty liver disease -- NASH nonalcoholic steatohepatitis -- FFAs free fatty acids -- AMPK AMP-activated protein kinase -- mTOR the mammalian target of rapamycin -- NF-κB nuclear factor-kappaB -- PTEN phosphatase and tension homologue deleted on chromosome 10 -- PPAR peroxisome proliferator-activated receptors -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- BSA bovine serum albumin -- DMEM Dulbeco's modified Eagle's medium -- FBS fetal bovines serum -- TG triglyceride -- AST aspartate transaminase -- ALT alanine aminotransferase -- PA palmitic acid -- OA oleic acid -- DMSO dimethyl sulfoxide; Non-alcoholic steatohepatitis -- Lipid accumulation -- Apoptosis -- Inflammation -- Hepato-protective effect -- AMPK signaling; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2023.105460
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Fatty acids-stimulated HepG2 cells reproduced NASH-characteristic features in vitro. Naringenin effectively ameliorated fatty acids-induced adversities in HepG2 cells. Four flavonoids were potential activators of AMP-activated protein kinase (AMPK). Involvement of enhanced AMPK activation, mTOR/NF-κBp65 interaction, PTEN expression. Abstract: Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease that lacks effective treatment. In this study, the anti-NASH effects of four flavonoids (pinocembrin, galangin, chrysin, and naringenin) rich in propolis were investigated in an in vitro NASH model established in free fatty acids (FFAs)-stimulated HepG2 cells. Using a co-treatment approach, our results showed that naringenin possessed the strongest anti-NASH efficacy by significantly counteracting FFAs-induced lipid accumulation, oxidative injuries, apoptosis, and secretion of pro-inflammatory IL-1β. Results from RNA-Seq revealed that co-treatment of naringenin significantly altered the expression profile of genes involved in lipid metabolism, apoptosis, and inflammatory responses in FFAs-stimulated HepG2 cells. The four flavonoids exerted their hepato-protective effects with the involvement of enhanced AMPK activation, mTOR-NF-κBp65 interaction, and PTEN expression. Moreover, molecular docking results showed that naringenin formed a stable complex with AMP-activated protein kinase (AMPK). Our results suggested that naringenin could be exploited as potential candidate for NASH treatment.