和木化癥汤抗肝癌关键成分及其免疫调节机制的网络药理学分析  

Effective components and immune regulation functions of He-Mu-Hua-Zheng decoction (HMHZD) in liver cancer: an integrative network pharmacologic-al analysis

作　　者：庄丽萍 陈春燕 刘荣[2] 陈晓蓉[3] 杨宗国[3] ZHUANG Li-ping;CHEN Chun-yan;LIU Rong;CHEN Xiao-rong;YANG Zong-guo(Department of Integrative Medicine,Fudan University Shanghai Cancer Center(Shanghai,200032),China;不详)

机构地区：[1]复旦大学附属肿瘤医院中西医结合科,上海200032 [2]上海市公共卫生临床中心药学部 [3]上海市公共卫生临床中心中西医结合科

出　　处：《中西医结合肝病杂志》2023年第11期1012-1016,共5页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：上海市公共卫生临床中心科研启动基金(No.KY-GW-2022-14)。

摘　　要：目的:基于网络药理学分析方法从“成分-靶点-通路”角度探讨和木化癥汤抗肝癌的物质基础及免疫调节功能。方法:通过TCMSP及Batman-TCM数据库筛选和木化癥汤的有效组分及其对应的药物作用靶点,在GeneCards、NCBI和DisGeNET数据库中筛选出肝癌的疾病靶点。通过STRING数据库构建和木化癥汤和肝癌的共同靶点的蛋白质-蛋白质相互作用(PPI)网络。通过Cytoscape软件对PPI网络及药物-疾病网络进行可视化展示。利用GSEA数据库探讨上述靶点的基因本体功能和KEGG通路富集分析。结果:通过数据库筛选,可获得和木化癥汤的268个基因靶点,4883个肝癌靶点基因,二者共同的靶点基因有197个。通过化合物-靶点网络和PPI网络筛选出与肝癌相关度较大的和木化癥汤核心成分是quercetin(槲皮素)、kaempferol(山柰酚)、wogonin(汉黄芩)、baicalein(黄芩素)、isorhamnetin(异鼠李素)及beta-sitosterol(β-谷甾醇)等,其核心靶点为MAPK1、AKT1、HSP90AA1、JUN、RELA、ESR1、FOS、MAPK14、IL-6及RXRA等。和木化癥汤参与肝癌T细胞及B细胞的活化、增殖、分化、迁移、自稳、凋亡及其调控过程,并涉及参与IL-17 signaling pathway、TNF signaling pathway、Th17 cell differentiation及Chemokine signaling pathway等信号通路。结论:和木化癥汤可通过调节T细胞及B细胞免疫功能发挥抗肝癌效应。Objective:Based on the integrative network pharmacological analysis,the material basis and immune regulation functions of He-Mu-HuA-Zheng Decoction(HMHZD)against liver cancer were addressed from the perspective of"component-target-pathway".Methods:The drug targets of the key ingredient of composed herbs in HMHZD were identified in the TCMSP and Batman-TCM databases,and the disease targets of liver cancer were screened in the GeneCards,NCBI,and DisGeNET databases.Protein-protein-interaction(PPI)analysis of the common targets of HMHZD and liver cancer were addressed in the STRING database.The protein interaction network and Drug-Disease network were constructed by the Cytoscape software.Topology analysis was performed via NetworkAnalyzer tool.Gene set enrichment analysis(GSEA)was used to execute the gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:Based on datA-mining,268 gene targets of HMHZD and 4883 disease targets of liver cancer were obtained,and 197 common targets between HMHZD and liver cancer were identified.The interaction of compound-target network and PPI network indicated that the core components of HMHZD that are more closely related to liver cancer are quercetin,kaempferol,wogonin,baicalein,isorhamnetin,and betA-sitosterol,etc.,and the core targets of HMHZD are MAPK1,AKT1,HSP90AA1,JUN,RELA,ESR1,FOS,MAPK14,IL-6,and RXRA,etc.Gene Ontology(GO)enrichment demonstrated that HMHZD is involved in regulations of the activation,proliferation,differentiation,migration,homeostasis,and apoptosis of T cells and B cells in liver cancer.KEGG enrichment showed that HMHZD is implicated in IL-17 signaling pathway,TNF signaling pathway,Th17 cell differentiation,and Chemokine signaling pathway.Conclusion:HMHZD can exert anti-HCC effect by regulating the immune functions of T cells and B cells.

关 键 词：肝癌 和木化癥汤 网络药理学 免疫调节 T细胞 B细胞 

分 类 号：R735.7[医药卫生—肿瘤]