Potential hepatotoxic mechanism of Polygoni multiflori caulis based upon network pharmacology and molecular docking technology
OBJECTIVE To explore the potential hepatotoxic mechanism of Polygoni multiflori caulis(PMC)through net-work pharmacology and molecular docking techniques.METHODS Based upon the literature data,the relevant databases of TCMSP,TCMID and HIT were searched for identifying the major active ingredients of PMC,as well as target proteins associ-ated with drug-induced liver injury(DILI).Intersection analysis of PMC/DILI targets was performed for acquiring core intersect-ing targets.Protein-protein interaction network,KEGG pathway and GO enrichment analyses were performed with information from core intersecting targets.Molecular docking was performed with AutoDock version 1.5.7.And the docking results were visualized with PyMOL software.Finally,the results were preliminarily validated through in vitro experiments,toxicology data-bases and in vivo experiments.RESULTS Network pharmacology indicated that PMC could interact with targets such as BCL2 and EGFR,leading to DILI through cancer and PI3K-AKT signaling pathways,etc.Important active ingredients included emo-din,chrysophanol and chrysophanol-8-O-β-D-glucopyranoside.Molecular docking results showed stable binding affinity between active ingredients and core targets.In vitro validation assays demonstrated cytotoxicity of emodin and physcion-8-O-β-D-glucoside.And in vivo validation assays revealed potential hepatotoxicity of emodin consistent with the screening results of net-work pharmacology.CONCLUSION Network pharmacology and molecular docking techniques are applied for a preliminary exploration of the components,mechanisms,targets and pathways of PMC-induced liver injury,providing data supports for fur-ther clinical application researches and elucidating the underlying mechanisms.
NETL
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万方数据
