中医药导报2025，Vol.31Issue(7)：16-24,9.DOI:10.13862/j.cn43-1446/r.2025.07.003
当归四逆汤加吴茱萸生姜汤及其核心成分山柰酚对肝癌机制的研究
Research on the Mechanism of Danggui Sini Tang Jia Wuzhuyu Shengjiang Tang(当归四逆汤加吴茱萸生姜汤)and Its Core Component Kaempferol on Liver Cancer
摘要
Abstract
Objective:To investigate the mechanism of Danggui Sini Tang Jia Wuzhuyu Shengjiang Tang(DSJWST)in combating liver cancer based on network pharmacology,molecular dynamics simulation,and immunohistochemistry.Methods:The active components and potential targets of the eight herbs in DSJWST were screened using the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Liver cancer-related targets were obtained from the GeneCards,OMIM,and TCGA databases,and the drug-disease intersection genes were identified through a Venn diagram.The String database was used to construct a protein-protein interaction(PPI)network,and the MCC algorithm in Cytoscape software was employed to identify key targets of DSJWST against liver cancer and to screen core components.The functions and pathways of the target proteins were analyzed through gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses.A"drug-core component-core target"network was constructed using Cytoscape.Molecular docking and molecular dynamics simulations were performed using the Pymol plugin and GROMACS 2016.4 software.Finally,immunohistochemical experiments were conducted to validate the expression of key liver cancer targets and their correlation with clinical prognosis.Results:A total of 1 599 active components and 4 124 liver cancer-related targets were screened,resulting in 166 intersection targets.Through the PPI network,10 key targets were selected,including IL6,TNF,STAT3,IL1B,AKT1,IFNG,TP53,NFKBIA,JUN,and CASP3.KEGG enrichment analysis revealed that the treatment of liver cancer by DSJWST was primarily associated with the AGE-RAGE signaling pathway,IL-17 signaling pathway,TNF signaling pathway,and HIF-1 signaling pathway.Molecular docking results showed that the docking binding energies of the 10 active components of DSJWST and 7 targets were all below-5.0 kcal/mol,indicating significant binding activity.Subsequently,kaempferol,which exhibited the highest binding energy,was selected for molecular dynamics simulation with CASP3.The results demonstrated that the structure of CASP3 tended to stabilize during its binding process with kaempferol.Meanwhile,immunohistochemical experiments confirmed that CASP3 was lowly expressed in liver cancer tissues and that it was associated with a favorable prognosis.Conclusion:Danggui Sini Tang Jia Wuzhuyu Shengjiang Tang may inhibit the progression of liver cancer by targeting CASP3 and subsequently mediating the activation of AGE-RAGE signaling pathway.关键词
肝癌/当归四逆汤加吴茱萸生姜汤/网络药理学/分子动力学模拟/CASP3Key words
liver cancer/Danggui Sini Tang Jia Wuzhuyu Shengjiang Tang/network pharmacology/molecular dynamics simulation/CASP3分类
医药卫生引用本文复制引用
梁楠,李峥,程紫轩,孙异强,牛杜升,黄博..当归四逆汤加吴茱萸生姜汤及其核心成分山柰酚对肝癌机制的研究[J].中医药导报,2025,31(7):16-24,9.基金项目
山西省自然科学研究面上项目(202103021224381) （202103021224381）
