Network pharmacology exploration and induction of liver cancer cell toxicity verification of alkaloids in Tripterygium Polyglycoside Tablet against liver cancer
Objective To investigate the mechanism of anti-liver cancer effects of alkaloidal components of Tripterygium Polyglycoside Tablet(TPT)based on network pharmacology combined with molecular docking technique and to validate the cytotoxicity-inducing effect of TPT alkaloidal components in liver cancer by cellular experiment.Methods The Swiss Target Prediction and Targetnet databases were used to predict the targets of nine alkaloidal components(wilforgine,wilforine,wilfortrine,wilfordine,wilfornine A,triptonine B,euonymine,peritassine A,euonine)in TPT.The targets of liver cancer were retrieved from the Genecards,OMIM and TTD databases,and the targets of alkaloidal components for the treatment of liver cancer was were obtained by inputting the two into the Venny online tool for intersection.The interaction network of"TPT-active ingredient-target-liver cancer"was constructed by Cytoscape software.Protein-protein interaction(PPI)network analysis of the intersecting targets was performed using the String database,Protein-protein interaction(PPI)network analysis of the intersecting targets was performed using the String database,and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)pathways was performed using the Metascape database.Molecular docking validation of the core targets and nine alkaloidal components was performed by using AutoDockTools and PyMol software.Verification of the cytotoxicity of nine alkaloids of TPT by CCK-8 assay in human liver cancer HepG2 cells in vitro.Results The screening yielded 119 potential targets of TPT alkaloidal components,1 168 liver cancer disease targets,and 23 intersecting targets.The PPI analysis identified ten key targets,including EGFR,CASP3,HSP90AA1,etc.The KEGG enrichment analysis mainly involved Pathways in cancer,Prostate cancer,PI3K-Akt signaling pathway,etc.The GO enrichment revealed that the TPT alkaloidal components promote apoptosis in liver cancer cells was associated with alteration of cell morphology and regulation of protein kinase activity.The molecular docking showed that multiple components have good binding ability to multiple key targets.Cellular validation experiments showed that five alkaloids(wilforgine,wilforine,wilfornine A,triptonine B,peritassine A)have cytotoxicity to HepG2 cells.Conclusion The nine alkaloidal components of TPT may act on key targets such as EGFR,CASP3,HSP90AA1 and modulate the APAF1/CASP9/CASP3 signaling pathway,thereby reducing cancer cell proliferation,activating the intrinsic apoptotic pathway in vivo and ultimately promoting apoptosis in liver cancer cells,having potential anti-liver cancer activity.
Tripterygium Polyglycoside Tabletalkaloidsnetwork pharmacologymolecular dockingHepG2 cellswilforginewilforinewilfomine Atriptonine Bperitassine A
NETL
NSTL
万方数据
维普
