白花蛇舌草-半枝莲药对治疗非小细胞肺癌的网络药理学研究

Network Pharmacological Study on Herbal Pair Baihuasheshecao(Hedyotis Diffusa Willd)-Banzhilian(Scutellariae Barbatae Herba)in Treating Non-Small Cell Lung Cancer

目的:利用网络药理学方法,研究白花蛇舌草-半枝莲药对治疗非小细胞肺癌(NSCLC)的分子机制。方法:检索中药系统药理学数据库和分析平台(TCMSP),筛选并预测白花蛇舌草-半枝莲药对的有效活性成分与作用靶点。检索人类基因数据库(GeneCards)获取与NSCLC相关的基因。结合网络构建与分析等相关方法,筛选白花蛇舌草-半枝莲药对治疗NSCLC的关键靶点。使用富集分析数据库(DAVID)对关键靶点进行基因本体论(GO)生物学过程分析与京都基因与基因组百科全书(KEGG)通路富集分析。结果:从TCMSP获取药对成分131种,按照药物代谢动力学(ADME)筛选出有效活性成分33种,预测作用靶点196个。挖掘GeneCards获取基因3015个。利用图形化显示网络分析和编辑软件(Cytoscape)分别构建活性成分与疾病的蛋白质-蛋白质相互作用网络,抽取合并网络后进行拓扑属性分析,筛选出关键靶点142个。对关键靶点进行GO生物学过程与KEGG通路富集分析显示,主要涉及265种生物学过程与114条信号通路,与NSCLC发生发展密切相关。结论:白花蛇舌草-半枝莲药对治疗NSCLC,具有多成分、多途径、多靶点的特点,其主要涉及RNA转录启动、细胞凋亡、细胞表皮生长、细胞增殖、T细胞调节等癌症相关生物学过程,并在多种癌症相关通路均有富集。

Objective:To study the molecular mecha-nism of herbal pair Baihuasheshecao(Hedyotis Diffusa Willd)-Banzhilian(Scutellariae Barbatae Herba)in the treatment of non-small cell lung cancer(NSCLC)by using network pharmacological method.Methods:The effective active ingredients and targets of herbal pair Baihuasheshecao-Banzhilian were screened and predicted by searching Traditional Chinese Medicine System Pharmacological Database and Analysis Platform(TCMSP).Genes related to NSCLC were obtained by searching the Database of Human Genes(GeneCards).Key targets of Baihuasheshecao-Banzhilian were screened for the treatment of NSCLC by combining network construction and analysis and other related methods.The Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to conduct Gene Ontology(GO)biological process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on key targets.Results:Total 131 kinds of herbal pair components were obtained from TCMSP,33 kinds of effective active components were screened according to Absorption Distribution Metabolism Excretion(ADME),and 196 targets were predicted.Total 3015 genes were obtained by mining GeneCards.Graphic Display Network Analysis and Editing Software(Cytoscape)were used to construct protein-protein interaction networks between active ingredients and diseases.After extracting and merging the networks,the topological attributes were analyzed,and 142 key targets were screened out.The GO biological process and KEGG pathway enrichment analysis of key targets showed that 265 biological processes and 114 signal pathways are mainly involved,which were closely related to the occurrence and development of NSCLC.Conclusions:Herbal pair Baihuasheshecao-Banzhilian has the characteristics of multiple components,multiple pathways and multiple targets for the treatment of NSCLC.It mainly involves cancer-related biological processes,such as:RNA transcription initiation,apoptosis,cell epidermal growth,cell proliferation,T cell regulation,etc.,and is enriched in a variety of cancer-related pathways.