The mechanism of didymin in alleviating non-alcoholic fatty liver disease in rats analyzed by the integrative analysis of untargeted metabolomics and network pharmacology
The mechanism of didymin in alleviating non-alcoholic fatty liver disease in rats analyzed by the integrative analysis of untargeted metabolomics and network pharmacology
Objective:To investigate the mechanism of didymin in alleviating lipid metabolism in non-alcoholic fatty liver disease(NAFLD)using integrative analysis of untargeted metabolomics and network pharmacology.Methods:The rats were randomly divided into normal group,model group and didymin group.The model group and didymin group were fed with a high-fat diet(HFD)for 8 weeks to induce NAFLD animal model,followed by the corresponding administration for further 8 weeks.Hematoxylin-eosin(HE)and Oil Red O staining were used to observe the cell morphology and lipid accumulation.Metabolomics of rat liver tissue was examined with high-resolution liquid chromatography-mass spectrometry(UPLC-QTOF/MS),and metabolism pathway was analyzed using Kyoto Encyclopedia of Genes and Genomes(KEGG)database.The overlapping target genes between didy-min and NAFLD were predicted by network pharmacology analysis,and the potential targets were further ana-lyzed by the integrative analysis of metabolomics and network pharmacology.Results:Didymin significantly re-duced liver injury and inhibited excessive lipid deposition in rats.Orthogonal partial least squares discriminant analysis(OPLS-DA)showed that significant differences in the metabolites between groups.The volcano plots in-dicated 404 differential metabolites between the normal group and the model group(293 up-regulated and 111 down-regulated),and 147 between the model group and the didymin group(95 up-regulated and 52 down-regulat-ed);metabolic pathway analysis showed that the differential metabolites were mainly enriched in the sphingolipid metabolism pathway.Network pharmacology analysis suggested that there was a total of 139 drug-disease com-mon targets,and further integrative analysis indicated that didymin could regulate the sphingolipid metabolism pathway and insulin resistance by affecting the target genes TNF,Bcl2,Mapk8,Pik3ca,Akt1,mTOR,Gsk3β,re-spectively.Conclusion:Didymin can regulate lipid metabolism disorder through the pathway of sphingolipid me-tabolism and insulin resistance,ultimately playing a role in the treatment of NAFLD.
维普
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