知柏地黄化裁方治疗中枢性性早熟的作用机制OA

Objective:To explore the major blood-absorbed components and the mechanism of Modified Zhibai Dihuang Formula for gona-dotrophin-dependent precocious puberty(GDPP)by UPLC-Q-TOF-MS/MS,network pharmacology,molecular docking and molecular dynamics simulation.Methods:A total of 12 SD rats were randomly divided into the blank group and the Modified Zhibai Dihuang For-mula group,with 6 rats in each group.The blank group was administered an equal volume of distilled water,while the Modified Zhibai Dihuang Formula group received 37.8 g·kg-1 of Modified Zhibai Dihuang Formula for 7 consecutive days.Blood samples were collect-ed 60 minutes after the last administration to prepare drug-containing serum.UPLC-Q-TOF-MS/MS was employed to identify blood-ab-sorbed components of Modified Zhibai Dihuang Formula.Targets of blood-absorbed components were retrieved from SwissTargetPredic-tion and TCMSP databases.Disease-related targets were obtained from GeneCards,OMIM,Drugbank and DisGeNET databases.Venny 2.1.0 online tool was used to acquire the intersecting targets between component-related targets and disease-related targets.Cytoscape 3.7.2 and STRING were applied to construct the"Modified Zhibai Dihuang Formula-blood-absorbed components-targets-GDPP"net-work and protein-protein interaction(PPI)network,so as to screen core components and key therapeutic targets of Modified Zhibai Di-huang Formula against GDPP.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analyses of intersecting targets were performed via Metascape.Autodock Vina was used for molecular docking between core components and key targets.SwissADME was adopted to evaluate gastrointestinal absorption and drug-likeness of core components,whereas pkCSM was used for toxicity assessment.GROMACS 2022 was utilized for molecular dynamics simulation.Results:A total of 32 blood-absorbed components were identified by UPLC-Q-TOMS/MS.Altogether 875 targets of blood-absorbed components were obtained from SwissTargetPrediction and TCMSP;3,121 GDPP-associated targets were collected from GeneCards,OMIM,Drugbank and DisGeN-ET,yielding 319 intersecting targets.Topological analysis indicated that tetrahydroberberine,alisol B acetate,saikosaponin B2,fraxetin,benzoylpaeoniflorin,saikosaponin A,timosaponin A-were core components,and AKT1,TP53,ESR1,IL-6 were key targets.GO enrich-ment analysis yielded 2,444 biological process terms,166 cellular component terms and 416 molecular function terms.A total of 220 pathways were enriched in KEGG analysis.Molecular docking results revealed favorable binding affinity between core components and key targets;timosaponin A1-ESR1 and benzoylpaeoniflorin-ALB exhibited the lowest binding energy.Molecular dynamics simulation demonstrated that timosaponin A1-ESR1 and benzoylpaeoniflorin-ALB possessed satisfactory structural stability and binding affinity.Conclusion:Components such as timosaponin A1 and benzoylpaeoniflorin in Modified Zhibai Dihuang Formula exert therapeutic effects on GDPP possibly by regulating targets including ESR1 and ALB.