The Effect And Mechanism For Protection Of Liver Injury In Mice Exposed To Chronic Alcohol By Dendrobium Officinale Flower Extracts

Alcoholic fatty liver(AFLD),caused by long-term drinking,is a worldwide disease.At present,there is no effective treatment in the clinic,and prevention methods are urgently needed.Dendrobium officinale flowers contain a variety of flavonoids,which have antioxidant activity and anti-inflammatory effects,and may protect the liver damage of mice with chronic alcohol exposure.Using mice models,the alleviative effect of Dendrobium officinale flower extracts(DOFE)for AFLD was studied.The mechanism of DOFE alleviating AFLD in mice was studied through analysis of the liver transcriptome,gut microbiota,and short-chain fatty acid metabolism of mice.The main research contents and results are as follows.(1)The alleviative effect of DOFE on AFLDC57BL/6 J mice were treated with Lieber-De Carli ethanol liquid feed and three doses of DOFE(15 mg/m L,30 mg/m L,60 mg/m L).Alcohol metabolism and liver injury-related indexes including aspartate transaminase(AST),alanine transaminase(ALT),and acetaldehyde(ALDH)were increased in the serum and liver of mice caused by alcohol exposure,and the activity of ethanol dehydrogenase(ADH)is decreased;Serum levels of inflammatory cytokines CYP2E1(cytochrome P450E1),tumor necrosis factor-α(TNF-α)and interleukin-6(Interleukin-6)increased significantly(P <0.05);The contents of oxidative stress factors including catalase(CAT),and malondialdehyde(MDA)were increased.The contents or activity of superoxide dismutase(SOD),glutathione(GSH),and glutathione peroxidase(GSH-Px)were reduced.The indexes were restored to normal after DOFE treatment,indicating that DOFE has the effect of alleviating AFLD in mice.(2)DOFE alleviating AFLD in mice through regulating liver gene expressionThe transcriptome of mice liver tissue was determined.It was found that gene expression in the control group and DOFE high-dose treatment were similar.It was speculated that high-dose DOFE supplementation restored the liver gene expression disorder caused by ethanol.Twenty-five differentially expressed genes were identified and related to lipid metabolism,among them,genes Cyp2b13,Cyp2c55,Cyp2j8,and Cyp39a1 belonging to the cytochrome P450 family were associated with lipid metabolism,inflammatory response,and liver injury.(3)DOFE alleviating AFLD in mice through regulating gut microbiotaAfter measuring the fecal microbiota of mice,it was found that alcohol exposure reduced the abundance of the Bacteroidetes phylum.After treatment with DOFE,the abundance of Bacteroido and Verrucomicrobia was increased.At the genus level,the abundance of beneficial bacteria Akkermansia was significantly increased(P < 0.05),while the abundance of harmful bacteria such as Blautia was decreased.The results showed that DOFE restored the disorder of gut microbiota induced by ethanol in mice.(4)DOFE alleviating AFLD in mice through regulating gut short-chain fatty acid metabolismCompared with the control group,the contents of caproic acid,valerate acid,butyric acid,isovalerate acid,and propionic acid significantly increased in mice exposed to alcohol(P < 0.05).The supplementation of DOFE reversed this trend,and the contents of caproic acid,valerate acid,and isovalerate acid were significantly decreased(P < 0.05).Correlation analysis showed that Alloprevotella abundance was negatively correlated with contents of acetic acid and isobutyric acid(P < 0.05),and Blautia abundance was positively correlated with the content of caproic acid(P < 0.05).In conclusion,this thesis found that DOFE can alleviate alcohol-induced AFLD,and its mechanism may be through affecting the expression levels of genes,e.g.,Cyp2b13,Cyp2c55,Cyp2j8,and Cyp39a1,increasing the abundance of Akkermansia,and affect the metabolism of short-chain fatty acids such as caproic acid,valerate acid,and isovalerate acid.This thesis reported the protective effect of DOFE on liver injury caused by chronic alcohol exposure in mice.Based on liver gene expression,gut microbiota,and short-chain fatty acid metabolism,the protective mechanism was identified,which provided the research basis for the development of functional food to prevent AFLD.