基于网络药理学探讨解毒抗癌方治疗原发性肝癌的作用机制  

Research on treating hepatocellular carcinoma with the Jiedu Kang’ai decoction based on network pharmacology

作　　者：黄永恒 赵昌林 HUANG Yongheng;ZHAO Changlin

机构地区：[1]广州中医药大学,广东广州510006 [2]广东祈福医院,广东广州511495 [3]广东药科大学,广东广州510006

出　　处：《中医临床研究》2022年第27期11-19,共9页Clinical Journal Of Chinese Medicine

基　　金：广东省中医药局科研项目(20191413);广州番禺区科技医疗卫生重大项目(2018-z04-01)。

摘　　要：目的:基于网络药理学研究解毒抗癌方治疗原发性肝癌(Hepatocellular Carcinoma,HCC)的主要活性成分与作用机制。方法:首先,通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索解毒抗癌方的主要有效成分及关联靶点;通过OMIM和GeneCard数据库检索HCC的主要靶点;通过R语言绘制韦恩图,筛取解毒抗癌方治疗HCC交集靶点;利用Cytoscape 3.8.2软件构建中药-活性成分-靶点相互作用网络。其次,利用String数据平台构建蛋白质-蛋白质相互作用(Present Pain Intensity,PPI)网络。最后,使用Bioconductor平台和R语言,进行基因本体论(Gene Ontology,GO)富集分析、京都基因、基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:解毒抗癌方治疗HCC的关键成分可能为槲皮素、木犀草素、汉黄芩素、柚皮素、黄芩素。关键靶点可能为丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、丝裂原活化蛋白激酶1(Mitogen-Activated Protein Kinase 1,MAPK1)、MAPK3、转录因子AP-1(Transcription Factor AP-1,JUN)、热休克蛋白90α编码基因(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、RELA癌基因(RELA Proto-Oncogene,NF-KB Subunit,RELA)等。GO和KEGG分析提示,解毒抗癌方治疗HCC的分子功能主要涉及DNA结合转录因子结合、RNA聚合酶II-特异性DNA结合转录因子结合、丝氨酸/苏氨酸蛋白激酶活性等。关键通路可能为磷脂酰肌醇-3-激酶(Phosphatidylinositol 3-hydroxy Kinase,PI3K)AKT通路、MAPK通路、白细胞介素-17(Interleukin-17,IL-17)通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)通路等。结论:解毒抗癌方主要抗癌物质基础是槲皮素和木犀草素,通过阻滞PI3K/AKT通路、MAPK通路、IL-17通路、TNF通路发挥作用。Objective:To explore the main active components and mechanism of the Jiedu Kang’ai decoction(解毒抗癌方)in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology.Methods:The main active ingredients and related targets of the Jiedu Kang,ai decoction were researched through Traditionnal Chinese Medicine System Pharmacology(TCMSP).The relevant disease targets of HCC were researched through OMIM and GeneCards database,and the intersecting targets of the Jiedu Kang’ai decoction for HCC were sieved by Venn diagrams drawn through R language.The traditional Chinese medicine-active ingredient-target regulation network was constructed by Cytoscape 3.8.2,and String platform was used to construct the protein-protein interactions(PPI)network.Finally,the Bioconductor platform and R language were used for Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results:The key components of the Jiedu Kang’ai decoction on HCC may be quercetin,luteolin,wogonin,naringenin,and baicalein.AKT,MAPK1,MAPK3,JUN,HSP90AA1,RELA,etc.,may be the key targets.GO and KEGG analysis showed that the Jiedu Kang’ai decoction on HCC involves the molecular functions such as DNA-binding transcription factor binding,RNA polymerase II-specific DNA-binding transcription factor binding,protein serine/threonine kinase activity,etc.;PI3K/AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.may be the key signaling pathway.Conclusion:The main anti-cancer material basis of the Jiedu Kang’ai decoction are quercetin and luteolin.And it works by blocking PI3K/AKT signaling pathway,MAPK signaling pathway,IL-17 signaling pathway and TNF signaling pathway.

关 键 词：解毒抗癌方 原发性肝癌 槲皮素 木犀草素 网络药理学 

分 类 号：R979.1[医药卫生—药品]