Effect of Laggera alata extract on alleviates metabolism-related fatty liver disease in mice by up-regulating Nrf2 signaling pathway
Objective To investigate the effect and potential molecular mechanism of Laggera alata extract on alleviates metabolism-related fatty liver disease(MAFLD)through network pharmacology and drug intervention.Methods The active ingredients of Laggera alata extract were analyzed through literature retrieval and the elated targets were predicted by SwissTargetPredicton and Pharm Mapper databases.MAFLD and oxidative stress-related targets were obtained by Genecards database.PPI network model was established and key targets were found by STRING and Cytoscape 3.9.1 software.Besides,GO enrichment analysis and KEGG pathway enrichment analysis were performed on the targets of hexagon chrysanthemum in the treatment of MAFLD.50 male sterile C57BL/6J mice were randomly divided into five groups after one week of adaptive feeding,which were control group,model group,low dose group,medium dose group and high dose group of Laggera alata extract.The experimental mice were given high-fat diet for MAFLD modeling,and the low,medium and high dose groups(1.25,2.50,and 5.00 g·kg-1)were given daily by gavage.Mice in each intervention treatment group were given ig administration once a day for six weeks.The mice were killed at the end of the 14th week of the experiment,and the liver index,liver tissue pathological changes,serum inflammatory factors and liver fat content,serum aminotransferase,liver fat level,oxidative damage index of liver malondialdehyde(MDA),reduced glutathione(GSH)and superoxide dismutase(SOD)levels and important genes and proteins of Nrf2 signaling pathway of the five groups of mice were compared.Expression levels of nuclear factor E2 associated factor 2(Nrf2),NAD(P)H quinoline oxidase 1(Nqo1),glycogen synthase kinase-3β(GSK-3β)and non-receptor tyrosine protein kinase(Fyn).Results A total of 304 intersection targets of Laggera alata,MAFLD and oxidative stress were obtained by network pharmacology.Laggera alata may act on HIF-1,AGE-RAGE,thyroid hormone,FoxO,PI3K-Akt and TNF signaling pathways in diabetic complications through core targets such as TNF,AKT1,ALB,EGFR,STAT3 and NFE2L2 to exert the therapeutic effect of MAFLD.Compared with the control group,the overall state of mice was poor,the liver tissues were large steatosis and lipid infiltration,and the serum aminotransferase and liver fat levels were significantly increased,which confirmed that the MAFLD model of mice was successfully constructed after eight weeks of high-fat diet.Liver index,liver pathological changes,liver fat level,serum aminotransferase,lipid peroxidation level and Nrf2 signaling pathway important gene and protein expression of mice in all drug intervention groups were significantly changed compared with model group,among which the changes were most obvious in high-dose group,and the results were statistically significant(P＜0.05).Conclusion Different doses of Laggera alata extract can significantly improve the levels of serum inflammatory factors,liver lipid deposition,liver function,and decrease liver index in MAFLD mice,which may be related to regulating the expression of Nrf2 signaling pathway,reducing the level of lipid peroxidation and the expression of inflammation in liver tissues.
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