摘要
目的:通过网络药理学方法和分子对接技术探讨黄芪黄酮类活性成分异鼠李素抗肿瘤作用及调控机制。方法:从中药系统药理学数据库与分析平台(TCMSP)数据库筛选出异鼠李素的靶点信息,Gene Cards数据库筛选出肿瘤相关靶点,通过R软件获得二者靶点交集。使用STRING在线数据库构建蛋白质-蛋白质相互作用网络,Cytoscape软件构建药理学调控网络,筛选出核心靶点。通过R语言进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)富集分析,分析作用靶点相关基因功能及信号通路。最后以活性成分异鼠李素为配体,与核心靶点进行分子对接分析以了解活性成分与核心靶点分子间的亲和力。结果:筛选出异鼠李素调控肿瘤的潜在靶点29个,其中雌激素受体(Estrogen Receptor,ESR)1、前列腺素氧化环化酶(ProstaglandinEndoperoxide Synthase,PTGS)2、RELA癌基因(RELA Proto-Oncogene,NF-KB Subunit,RELA)、雄激素受体(Androgen Receptor,AR)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)等为核心靶点。GO富集分析结果显示,这些基因主要集中在类固醇激素、酮类、RNA聚合酶II特异性DNA结合转录因子结合、DNA结合转录因子结合方面。KEGG富集分析结果显示雌激素、细胞衰老、催乳素、白细胞介素(Interleukin,IL)-17、前列腺癌、小细胞肺癌等信号通路可能是异鼠李素调肿瘤的关键通路。分子对接结果显示,异鼠李素与核心靶点基因均具有较强的亲和力。结论:网络药理学分析结果发现了异鼠李素调控肿瘤的潜在靶点,并可通过ESR1、PTGS2、RELA、AR、PPARG等多个靶点所在信号通路发挥抗肿瘤作用。
Objective:To explore the tumor regulation mechanism of isorhamnetin in astragalus membranaceus by using network pharmacology and molecular docking analyses.Methods:TCMSP database was used to predict all the action targets of isorhamnetin and GeneCard database was used to retrieve tumor-related disease targets.Then,the network of active molecules and targets of tumors was pictured by R software.With the help of STRING online database the PPI network was drawn,and then the Cytoscape software was used to make the pharmacological regulatory network,and selected the main targets.The GO enrichment analysis and KEGG pathway analysis of the isorhamnetin-tumor identical genes were performed by R software to analyze the possible gene function and signal pathway of target.The active ingredient isorhamnetin was used as the ligand for molecular docking with the selected core target,in order to prove the affinity between the active ingredient and the core target.The results of molecular docking indicated that the molecular interaction between isorhamnetin and targets was strong.Results:A total of 29 potential tumor regulatory targets were screened out in this study,including ESR1,PTGS2,RELA,AR,PPARG and so on.The results of GO enrichment analysis showed that these genes were mainly enriched in steroid hormones,ketones,RNA polymerase II specific DNA binding transcription factor binding,DNA binding transcription factor binding.The results of KEGG pathway analysis showed that prolactin signaling pathway,estrogen signaling pathway,cellular senescence signaling pathway,IL-17 signaling pathway,prostate cancer signaling pathway,small cell lung cancer signaling pathway were the possible key pathway of isorhamnetin regulating tumor.Conclusion:The results of network pharmacology and molecular docking analysis suggest isorhamnetin has potential anti-tumor effects through ESR1,PTGS2,RELA,AR,PPARG signaling pathways.
出处
《中医临床研究》
2023年第20期38-42,共5页
Clinical Journal Of Chinese Medicine
关键词
黄芪异鼠李素
肿瘤
网络药理学
分子对接
Astragalus isorhamnetin
Tumor
Network pharmacology
Molecular docking
