健脾消渴方干预2型糖尿病的物质基础及潜在作用机制研究OA

Objective It is to explore the potential mechanism of wasting-thirst decoction for fortifying spleen(WT-DFS)in the treatment of type 2 diabetes(T2DM)by network pharmacology,molecular docking and untargeted metabolo-mics.Methods ①The effective chemical components of WTDFS were mined from BATMAN-TCM database;the T2DM tar-gets and their common targets shared with WTDFS were screened out from GeneCards database;the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed on OmicShare plat-form;a protein-protein interaction(PPI)network was constructed on STRING platform and the core targets were analyzed by Cytoscape topological parameters;the batch molecular docking was performed through AutoDock vina.②Eighty male SD rats were selected,20 of which were randomly assigned to the normal group,and the remaining rats were prepared to estab-lish models of T2DM.The successfully modeled rats were randomly divided into model group,WTDFS group and metformin group,with 20 rats in each group.The WTDFS group was given WTDFS 20 g/kg via gavage,the metformin group was giv-en metformin 200 mg/kg by gavage,and the normal group and model group were given an equal volume of distilled water via gavage,all once daily,continuously treated for 4 weeks.The differentially expressed metabolites in the serum of rats in each group were detected by non-targeted metabolomics techniques,and bioinformatics data mining was performed.Results①There were 95 effective ingredients in WTDFS,corresponding to 407 targets,and 3024 targets corresponding to T2DM,a total of 190 common targets were shared between T2DM and WTDFS;the GO and KEGG enrichment results showed that they were mostly concentrated in metabolic field;PPI network and topological analysis showed that the core targets were NOS1,CACNG2,PRKCA,CACNA1C and DLG4;molecular docking results indicated that the main active ingredients had good binding strength with the core targets.②The main differentially expressed metabolites in the serum of rats in the mod-el group and WTDFS group were Phloretin 2'-O-glucuronide,Paeonol,etc.,which were closely related to signaling path-ways such as bile secretion signaling pathway,glucagon signaling pathway,cAMP signaling pathway.Conclusion WTDFS plays a therapeutic effect in the treatment of T2DM via regulating signal pathways such as cAMP pathway.