摘要
It is now well established that alcoholic liver disease is associated with oxidative stress and inflammatory reactions.4-Methylguaiacol(4 MG)is a phenolic lignin model compound found in many foods.In this study,the effect of 4 MG on antioxidant capacity was evaluated and the molecular mechanisms of autophagy and the Keap1-Nrf2 signaling pathway were explored in vitro and in vivo.The in vitro results showed that 4 MG possessed strong free radical scavenging capabilities in LO2 cells treated with 2,2′-azobis-2-methyl-propanimidamide(AAPH)by dramatically repressing the expression of malondialdehyde and upregulating superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px).Under both starvation and full nutrition conditions,pretreatment of LO2 cells with 4 MG remarkably increased the level of autophagy by promoting the expression of microtubule-associated protein 1 light chain 3-II(LC3-II)and decreasing the level of sequestosome-1(p62)protein.Additionally,when exposed to AAPH,4 MG further promoted the expression of LC3 at the mRNA level,while IL-1β,IL-6,NF-κB,and TNF-αwere inhibited.This result was confirmed by a fluorescence confocal experiment.The in vivo results further revealed that the administration of 4 MG significantly attenuated serum liver enzyme and lipid levels in alcoholic liver injury mouse model.Meanwhile,the levels of serum high-density lipoprotein-cholesterol and hepatic SOD,CAT,and GSH-Px were upregulated.Autophagy was promoted after the administration of 4 MG compared with the enhanced autophagy group(Torin1 group).Furthermore,the entry of Nrf2 protein into the nucleus was accompanied by a reduction of Keap1 and the increased expression of the downstream heme oxygenase 1(HO-1).These results revealed that 4 MG partially improved the antioxidant capacity through the Keap1-Nrf2 pathway in the liver.Thus,4 MG is a natural product with potentially liverprotective effects.
基金
funded by the National Natural Science Foundation of China(Grant No.32060532)
the National Key Research and Development Program(Grant No.2021YFE0192000).
作者简介
co-first authors of the article:Anjun Li;co-first authors of the article:Shanbin Chen;Corresponding authors:Chunguang Luan.E-mail addresses:chunguangluan@163.com;Corresponding authors:Deliang Wang,wdlpost@163.com。
