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

In order 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 to analyze the active components of SVWS to clarify its chemical composition. The potential targets of these bioactive components were predicted by 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. Further, the "drug-component-target" network was constructed via Cytoscape 3.10.3, the protein-protein interaction (PPI) network was built by 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. The molecular docking was accomplished with AutoDockTools 1.5.6 software, and the results were visualized by PyMOL 2.6. The results showed 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. The GO enrichment analysis revealed thatd the core targets were mainly enriched in the following biological processes, cellular components and molecular functions: the biological processes included positive regulation of transcription by RNA polymerase Ⅱ, positive regulation of DNA-templated transcription and positive regulation of gene expression; the cellular components involved cytosol, nucleus and cytoplasm; the molecular functions included homologous protein binding, enzyme binding and DNA-binding transcription factor activity. The KEGG pathway enrichment analysis indicated that the core targets were primarily enriched in the signaling pathways such as Hepatitis B, Lipid and atherosclerosis, IL-17 signaling pathway, cancer pathway, and AGE-RAGE signaling pathway in diabetic complications. The results of molecular docking showed that the core components could bind stably to the core targets, with all binding affinities lower than -5.0 kcal/mol. In conclusion, the bioactive components of the Water-extracted Supernatant of Sanghuangporus vaninii exerted the hypoglycemic effects through a multi-component, multi-target and multi-pathway mode. It was speculated that the six core bioactive components in SVWS (6,7,4-trihydroxyflavanone, sonchifolin, epilubimin, hesperetin, pinobanksin acetate, and pinostrobin) may exert the 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), which provided a reference for the development of natural drugs with hypoglycemic effect.