Study on the Hypoglycemic Effect Mechanismof the Water-extracted Supernatant of Sanghuangporus vaninii by UPLC-MS/MS and Network Pharmacology

To investigate the bioactive components of the Water-extracted Supernatant of Sanghuangporus vaninii（SVWS）and its hypoglycemic mechanism, an ultra-high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）approach was employed for component analysis. The potential targets of these bioactive components were predicted using the SwissADME and SwissTargetPrediction databases, while the targets associated with type 2 diabetes mellitus（T2DM）were retrieved from the GeneCards, DrugBank and OMIM databases. The intersection of component targets and disease targets was obtained to identify the potential therapeutic targets of SVWS for T2DM. The "drug-component-target" network was constructed via Cytoscape 3.10.3, the protein-protein interaction（PPI）network was built using the STRING database, and Gene Ontology（GO）functional enrichment analysis as well as Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed on the DAVID database. Molecular docking was accomplished with AutoDockTools 1.5.6, and the results were visualized by PyMOL 2.6.The results demonstrated that a total of 1,453 compounds were identified in the Water-extracted Supernatant of Sanghuangporus vaninii by UPLC-MS/MS. Through database screening and prediction, 507 bioactive components and 955 potential targets of SVWS for T2DM treatment were obtained. GO enrichment analysis revealed that the core targets were mainly enriched in the following biological processes, cellular components and molecular functions: biological processes included positive regulation of transcription by RNA polymerase II, positive regulation of DNA-templated transcription and positive regulation of gene expression; cellular components involved cytosol, nucleus and cytoplasm; molecular functions comprised identical protein binding, enzyme binding and DNA-binding transcription factor activity. KEGG pathway enrichment analysis indicated that the core targets were primarily enriched in Hepatitis B, Lipid and atherosclerosis, IL-17 signaling pathway, Pathways in cancer, and AGE-RAGE signaling pathway in diabetic complications. Molecular docking results showed that the core components could bind stably to the core targets, with all binding affinities lower than -5.0 kcal·mol^-1.In conclusion, the bioactive components of the Water-extracted Supernatant of Sanghuangporus vaninii exert hypoglycemic effects through a multi-component, multi-target and multi-pathway mode. It is speculated that six core bioactive components in SVWS（6,7,4-Trihydroxyflavanone, Sonchifolin, Epilubimin, Hesperetin, Pinobanksin acetate, Pinostrobin）may exert hypoglycemic effects by regulating the Hepatitis B and Lipid and atherosclerosis signaling pathways via eleven key target proteins（PPARG, AKT1, GAPDH, PTGS2, TNF, IL6, IL1B, CXCL8, MAPK1, MAPK3 and MAPK14）. This study provides a theoretical basis for the development of natural hypoglycemic drugs.