Applying the UPLC-Zone TOF-MS/MS combined network pharmacology to explore the effects of MFS intervention on NAFLD.

The mechanism of MaiFuSheng (MFS) on inhibiting Nonalcoholic Fatty Liver Disease (NAFLD) were investigated based on the exploration of chemical compositions, the techniques of network pharmacology and molecular docking, and the validation using NAFLD mice model. The components of MFS were identified through UPLC-Zeno TOF-MS/MS. The Swiss Bioinformatics Research Platform were applied to obtain active components and potential targets of MFS. The DisGeNet and OMIM databases were used to screen disease targets of NAFLD. The intersection between disease targets and potential targets of MFS were obtained from Venn diagram, which were analyzed by constructing cross-target protein-protein interaction (PPI) network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted on Metascape database. The molecular docking about core targets and active components of MFS were carried out. Using high-fat diet (HFD)-induced C57BL/6J mice as NAFLD animal model to validate key targets. A total of 130 compounds were recognized, 54 active constituents and 176 potential targets of NAFLD were collected. The molecular docking experiments for the top 10 components with the targets are based on the degree value. We found docking models with the best binding energy for TNF-α with Quercetin, IL-17 with Asiatic acid, and IL-1β with Quercetin. We applied qPCR technique to detect above inflammation and lipid metabolism related indicators. Enrichment analysis demonstrated that MFS protects NAFLD via biological processes such as fatty acid transformation and positive regulation of lipid metabolism, as well as signaling pathways such as AGE-RAGE, HIF-1, and IL-17. Compared to the control groups, the model group's ALT, TG, and LDL-C indicators increased, whereas HDL-C indicators dropped (P<0.05) . MFS and Simvastatin treatment groups significantly reduced body weight, liver weight, and fat weight compared to the model groups (P<0.05). Higher doses resulted in significant reductions in serum levels and expression of TNF-α, IL-1β, and IL-17 (P<0.01). Compared to the control groups, the MFS treatment groups can minimize liver lipid accumulation by modulating the expression of lipid metabolism-related genes and improving hepatic fat breakdown. [ABSTRACT FROM AUTHOR]