Myricitrin ameliorates ethanol-induced steatosis in mouse AML12 liver cells by activating AMPK, and reducing oxidative stress and expression of inflammatory cytokines

Abstract

It is necessary to identify compounds that may provide protection against alcoholic liver disease. To the best of our knowledge, the effect of myricitrin on the development of ethanol‑induced liver disease has not been previously investigated. The present study aimed to determine the effect of myricitrin on ethanol‑induced steatosis in AML12 mouse liver cells and to identify the underlying molecular mechanisms. Ethanol‑treated AML12 cells exhibited significant improvement in viability following treatment with myricitrin. Oil red O staining indicated that myricitrin ameliorated ethanol‑induced lipid accumulation in cells. Furthermore, following treatment with myricitrin, improvement in ethanol‑induced steatosis and decrease in the levels of reactive oxygen species and lipoperoxides were observed in ethanol‑stimulated cells. Myricitrin suppressed mRNA and protein expression of tumor necrosis factor‑α, interleukin‑6 and transforming growth factor‑β1 in ethanol‑stimulated AML12 cells. Myricitrin markedly increased phosphorylation of adenosine monophosphate‑activated protein kinase (AMPK) and significantly reduced mRNA expression of sterol‑regulatory element‑binding protein‑1c (SREBP‑1c) and fatty acid synthase in ethanol‑stimulated AML12 cells. The results of the present study indicate that myricitrin ameliorates ethanol‑induced steatosis in AML12 cells by attenuating oxidative stress, suppressing expression of certain inflammatory cytokines and modulating the AMPK/SREBP-1c pathway.

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

“…As shown in Fig 3A-3G, we also observed that GPS reversed ethanol-induced lipid accumulation by inhibiting lipid synthesis and promoting lipid oxidation in AML12 mouse hepatocyte cell line via LKB1-AMPK, which is consistent with previous work performed in HepG2 cells and primary mouse hepatocytes (Li et al, 2018). Our in vitro data related to ethanol-treated steatotic AML12 cells was also in line with previously published literature (Gao et al, 2018). These data hinted that GPS protected against liver steatosis induced by chronic ethanol consumption.…”

Plant‐Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

“…The administration of resveratrol from fruits could alleviate AFLD in HepG2 cells by activating the AMPK-lipin1 signaling pathway, accompanied by the decreased expression of SREBP-1c and lipin1 [92]. Similarly, some natural flavonoids (like myricetin and myricitrin) extracted from berries could alleviate alcoholinduced lipid accumulation, oxidative stress, and inflammation in AML12 cells by enhancing the phosphorylation of AMPK and reducing the expression of FAS and SREBP-1c [93,94].…”

Potential therapeutic use of plant flavonoids in AD and PD

“…Myricitrin (C 21 H 20 O 12 ), 3, 5, 7, 3′, 4′, 5′-hexahydroxyflavone 3-O-rhamnoside, the glycoside of myricetin, is abundant in the root bark of Myrica cerifera , Myrica esculenta , Ampelopsis grossedentata , Nymphaea lotus , and Chrysobalanus icaco . This compound possesses anti-oxidative, anti-inflammatory, and anti-nociceptive, and neuro-protective activities [ 209 ]. Studies have identified that, like myricetin, myricitrin could reduce MPP + -induced mitochondrial dysfunction, prevent 6-OHDA-induced mitochondrial oxidation, restore mitochondrial damage, ameliorate apoptosis dysfunction, and protect against DA neurotoxicity through DJ-1 activity [ 210 , 211 ].…”