基于网络药理学与分子对接探讨广藿香抗肝癌作用机制  

Mechanism of Pogostemonis Herba in treatment of liver cancer based on network pharmacology and molecular docking

作　　者：曹扶胜 刘经健 杨洋 温若君 任芳玲[2] 陈琴华 CAO Fusheng;LIU Jingjian;YANG Yang;WEN Ruojun;REN Fangling;CHEN Qinhua(Shiyan Hospital of Integrated Traditional and Western Medicine,Shiyan 442000,China;Sinopharm Dongfeng General Hospital,Hubei University of Medicine,Shiyan 442000,China;Bao’an Authentic TCM Therapy Hospital,Shenzhen 518101,China)

机构地区：[1]十堰市中西医结合医院,湖北十堰442000 [2]湖北医药学院附属国药东风总医院,湖北十堰442000 [3]深圳市宝安纯中医治疗医院,广东深圳518101

出　　处：《现代药物与临床》2024年第7期1739-1746,共8页Drugs & Clinic

基　　金：湖北省中医药管理局2023—2024年度中医药科研项目(ZY2023M037);深圳市“医疗卫生三名工程”项目(SZZYSM202106004);深圳市宝安区医疗卫生基础研究项目(2021JD166);国药东风总医院青年人才项目(2023Q01,2023Q02)。

摘　　要：目的 基于网络药理学与分子对接技术探讨广藿香抗肝癌的作用靶点及信号通路,阐明其可能的作用机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)数据库检索广藿香的化学成分、作用靶点,运用Uniprot数据库对靶点名称进行规范,利用GeneCards数据库及OMIM数据库收集肝癌作用靶点,使用Venny 2.1网站将广藿香作用靶点与肝癌靶点取交集,通过STRING平台构建蛋白质相互作用(PPI)网络图,采用DAVID网站进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。通过Cytoscape 3.8.2软件用于构建“药物–活性成分–靶点–疾病”网络,筛选出核心靶点,并将活性成分与排名前5位的核心靶点进行分子对接。结果 筛选出10个广藿香主要活性成分及165个活性成分作用靶点,123个交集靶点。核心靶点为蛋白激酶B(Akt)、肿瘤蛋白P53(TP53)、白细胞介素-6(IL-6)、转录因子AP-1(JUN)、半胱氨酸天冬氨酸蛋白酶(CASP3)。GO分析表明广藿香对肝癌的治疗作用主要涉及RNA聚合酶Ⅱ启动子转录的正调控、转录的正调控和DNA模板化等283条生物过程,蛋白质结合、相同蛋白质结合和RNA聚合酶Ⅱ核心启动子近端区序列特异性DNA结合等57个分子功能,核和胞质溶胶等26个细胞组分;KEGG富集分析得到95条信号通路,主要包括癌症通路、乙型肝炎、人类T淋巴细胞病毒Ⅰ(HTLV-I)感染、肿瘤蛋白、磷脂酰肌醇3-激酶(PI3K)/Akt等信号通路。分子对接结果显示,广藿香有效成分能够与核心靶点有效结合。结论 广藿香可通过作用于Akt1、TP53、IL-6、JUN、CASP3等靶点,调控乙型肝炎、HTLV-I感染、PI3K/Akt等信号通路发挥肝癌治疗作用。Objective To analysis the targets,signal pathways and possible mechanisms of action of Pogostemonis Herba in treatment of liver cancer based on the method of network pharmacology and molecular docking.Methods The TCMSP database was used to screen the chemical components and targets of Pogostemonis Herba,the Uniprot database was used to query the corresponding genes of the target,the Genecards database and the online human Mendelian Inheritance(OMIM)database were used to collect the targets of liver cancer.Venny 2.1 was used to intersect the target of Pogostemonis Herba and the target of liver cancer,and build a protein interaction(PPI)network through the STRING platform.DAVID was used for GO enrichment analysis and KEGG analysis.Visual analysis was performed by Cytoscape 3.8.2 software.Cytoscape 3.8.2 software was used to construct the“drug-active ingredient-target-disease”network,screen out the core targets,and docked the active ingredients with the top five core targets.Results 10 Compounds and 165 corresponding targets were screened from Pogostemonis Herba medicinal materials.123 Key targets were obtained by intersecting the regulatory targets of the main active components of Pogostemonis Herba and the targets of liver cancer.Akt,TP53,IL-6,JUN,and CASP3 were key targets.The GO analysis showed that the therapeutic effect of Pogostemonis Herba on liver cancer mainly involves 283 biological processes such as positive regulation of transcription from RNA polymeraseⅡpromoter and positive regulation of transcription,DNA-templated,57 molecular functions such as protein binding,identical protein binding,and RNA polymeraseⅡcore promoter proximal region sequence-specific DNA binding,as well as 26 cellular components such as nucleus and cytosol;Through KEGG enrichment analysis,95 signaling pathways were identified,mainly including pathways in cancer,hepatitis B,HTLV-I infection,tumor proteins,PI3K/Akt,and other signaling pathways.The effective components of Pogostemonis Herba can effectively combine with core tar

关 键 词：广藿香 肝癌 网络药理学 分子对接 蛋白激酶B 肿瘤蛋白P53 白细胞介素-6 芫花素 尼泊尔鸢尾异黄酮 菲酮 广藿香酮 

分 类 号：R285.5[医药卫生—中药学]