基于网络药理学和分子对接探究莪术-三棱药对治疗前列腺癌的作用机制  

Mechanism of the medicine pair of Ezhu-Sanleng in the treatment of prostate cancer based on network pharmacology and molecular docking

作　　者：张蝶 刘曾晶 蒙秋霞 王慧丰 胡艳玲[1,4,5] ZHANG Die;LIU Zengjing;MENG Qiuxia;WANG Huifeng;HU Yanling(Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry,Guangxi Medical University,Nanning 530022,China;School of Information and Management,Guangxi Medical University,Nanning 530022,China;Department of Human Anatomy,School of Basic Medical Sciences,Guangxi Medical University,Nanning 530022,China;Life Sciences Institute,Guangxi Medical University,Nanning 530022,China;Research Centre for Genomic and Personalized Medicine,Guangxi Medical University,Nanning 530022,China)

机构地区：[1]广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心,南宁530022 [2]广西医科大学信息与管理学院,南宁530022 [3]广西医科大学基础医学院人体解剖学教研室,南宁530022 [4]广西医科大学生命科学研究院,南宁530022 [5]广西医科大学基因组与个性化医学研究中心,南宁530022

出　　处：《数理医药学杂志》2024年第1期22-33,共12页Journal of Mathematical Medicine

基　　金：广西医科大学青年科学基金项目(GXMUYSF202307)。

摘　　要：目的探究莪术-三棱药对治疗前列腺癌(prostate cancer,PCa)的药物活性成分、核心靶点及分子机制。方法基于HERB和PubChem数据库获取莪术-三棱的药物活性成分和作用靶点,利用Genecards、OMIM、PhamGkb、TTD、DrugBank数据库获取PCa疾病靶点,药物靶点和疾病靶点取交集得到共同靶点。采用Cytoscape 3.9.0软件构建莪术-三棱活性成分与PCa靶点网络,将交集靶点导入String数据库构建蛋白-蛋白相互作用网络(protein-protein interaction network,PPI),对潜在靶点进行基因本体(gene gontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,最后利用AutoDockTools 1.5.7等软件对核心靶点和药物关键活性成分进行分子对接验证。结果共筛选得到72种药物活性成分和760个有效活性成分靶点,PCa疾病相关靶点13001个,交集靶点为659个。药物关键核心成分为莪术双环烯酮、无患子皂苷B、花椒麻素、(2s)-3',4'-亚甲二氧基-5,7-二甲氧基黄酮、芹菜素、天人菊内酯、山奈酚、三棱酸、脱甲氧姜黄素以及5,7,2',3'-四羟基黄酮。PPI网络分析得到SRC、TP53、MAPK3、MAPK1、STAT3、HSP90AA1、AKT1、PIK3R1、RHOA、GRB2核心靶点。GO和KEGG富集分析显示,莪术-三棱治疗PCa主要涉及细胞增殖、凋亡、迁移和信号转导等信号通路。分子对接结果显示核心靶点与活性成分之间存在较强的结合力。结论本研究揭示了莪术-三棱抗PCa的关键活性成分及其与潜在靶点的相互作用,凸显了其多成分、多靶点相互作用的特性,为深入研究莪术-三棱治疗PCa提供了有价值的参考。Objective To explore the pharmacologically active components,core targets,and molecular mechanism of the medicine pair of Ezhu-Sanleng in the treatment of prostate cancer(PCa).Methods The pharmacologically active components and target interactions of Ezhu-Sanleng were obtained based on the HERB and PubChem databases.The disease targets of PCa were obtained from Genecards,OMIM,PharmGkb,TTD,and DrugBank databases.The common targets were identified by taking the intersection of drug targets and disease targets.The Ezhu-Sanleng active components and PCa targets network was constructed by Cytoscape 3.9.0 software.The intersection targets were imported into the STRING database to build a protein-protein interaction network(PPI).Gene gontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted on potential targets.Finally,molecular docking validation of core targets and key pharmacologically active components was performed by AutoDockTools 1.5.7 software and other softwares.Results A total of 72 pharmacologically active components and 760 effective active component targets were screened.There were 13001 disease-related targets for PCa and the intersection targets were 659.The key core components of the drug included curcumenone,sapindoside B,sanshool,(2s)-3',4'-methylenedioxy-5,7-dimethoxyflavane,apigenin,gaillardin,kaempferol,Sanleng acid,demethoxycurcumin,and 5,7,2',3'-tetrahydroxyflavone.PPI network analysis identified SRC,TP53,MAPK3,MAPK1,STAT3,HSP90AA1,AKT1,PIK3R1,RHOA,and GRB2 as core targets.GO and KEGG enrichment analyses showed that Ezhu-Sanleng in the treatment of PCa mainly involved signaling pathways related to cell proliferation,apoptosis,migration,and signal transduction.Molecular docking results revealed a strong binding affinity between the core targets and active components.Conclusion This study elucidated the key active components of Ezhu-Sanleng and their interactions with potential targets in the anti-PCa context.It highlights

关 键 词：莪术-三棱 药对 前列腺癌 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]