首页|Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway
Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway
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Inula britannica ameliorates alcohol-induced liver injury by modulating SIRT1-AMPK/Nrf2/NF-κB signaling pathway
Objective:Inula britannica is a traditional Chinese medicinal and functional food with various effects such as anti-liver injury,hypoglycemia,antioxidants,and anti-tumor.The aim of this study was to investigate the protective effects and mechanisms of the ethanolic extract of I.britannica(EEIB)on alcohol-induced liver injury in mice.Methods:Fifty-six female C57BL/6 mice were randomly divided into seven groups:control group(Con),ethanol feeding model group(EtOH),Silibinin positive treatment group(EtOH+Silibinin 100 mg/kg),EEIB treatment group(EtOH+EEIB 100,200,and 400 mg/kg),and EEIB control group(EEIB 400 mg/kg).The National Institute on Alcohol Abuse and Alcoholism(NIAAA)ethanol-feeding model was used to study the effects of EEIB on alcohol-induced lipid metabolism,inflammation,oxidative stress,and fibril formation in mice by histopathological evaluation,immunofluorescence staining,Western blotting anal-ysis and molecular docking.Results:EEIB reduced liver indices to different degrees to normal levels and improved liver morphology in mice.EEIB inhibited alcohol-induced liver injury by activating the sirtuin 1(S1RT1)-adenosine monophosphate-activated protein kinase(AMPK)signaling pathway in the liver of alcohol-fed mice,in which sesquiterpenes may be the potential active ingredients,and also down-regulated the expression of alpha-smooth muscle actin(α-SMA),collagen alpha(Collagen I),tumor necrosis factor-alpha(TNF-α)and attenuated alcohol-induced liver injury.In addition,EEIB also activated the nuclear factor ery-throid 2-related factor 2(Nrf2)signaling pathway,which alleviated alcohol-induced liver injury at the level of oxidative stress.Notably,the EEIB control group demonstrated that EEIB had no toxic effects in mice.EEIB reduced alcoholic liver injury in a dose-dependent manner.Its therapeutic efficacy was comparable to,if not better than,that of Silibinin when administered at a dose of 400 mg/kg.Conclusion:EEIB showed significant therapeutic effects on alcohol-induced liver injury in mice,and its mechanism of action was related to the SIRT1-AMPK,nuclear factor-kappa B(NF-κB),and Nrf2 signaling pathways,in which sesquiterpenes may be the potential active ingredients.
alcoholic liver injuryinflammationInula britannica L.sesquiterpenesSIRT1-AMPK/Nrf2