基于网络药理学和分子对接技术探讨柴胡-黄芩药对治疗癌性发热的作用机制  

Exploration of Radix Bupleuri-Radix Scutellariae herb pair for the treatment of cancerous fever:a mechanism study based on network pharmacology and molecular docking technique

作　　者：谢虹亭 谢飞宇 龙思丹 陈美池 薛鹏 朱世杰[2] XIE Hong-ting;XIE Fei-yu;LONG Si-dan;CHEN Mei-chi;XUE Peng;ZHU Shi-jie(Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Oncology,Wang Jing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]北京中医药大学研究生院,北京市100029 [2]中国中医科学院望京医院肿瘤科,北京市100102

出　　处：《广西医学》2022年第23期2771-2779,共9页Guangxi Medical Journal

基　　金：国家自然科学基金(81973640)。

摘　　要：目的基于网络药理学和分子对接技术探讨柴胡-黄芩药对治疗癌性发热的作用机制。方法利用中药系统药理学数据库与分析平台搜索柴胡、黄芩的活性化学成分及其作用靶点,并应用GeneCards数据库、OMIM数据库、TTD数据库获得癌性发热相关靶点。对柴胡、黄芩活性化学成分相关靶点与癌性发热相关靶点进行取交集;针对交集靶点,利用STRING 11.0数据库及CytoScape 3.7.2软件建立蛋白质-蛋白质相互作用网络及推测网络中的潜在蛋白质功能模块,并基于Metascape平台进行基因本体论(GO)功能富集分析与京都基因与基因组百科全书(KEGG)通路富集分析。利用CytoScape 3.7.2软件建立药物成分-交集靶点-通路网络图,并根据拓扑参数推断柴胡-黄芩药对治疗癌性发热的核心活性化学成分、核心靶点、核心通路;利用AutoDock1.5.6软件对上述核心活性化学成分和核心靶点进行分子对接。结果(1)共得到柴胡-黄芩药对的42个活性化学成分和178个作用靶点,癌性发热相关靶点1562个,交集靶点98个,2个潜在蛋白质功能模块。(2)GO功能富集分析提示交集靶点主要涉及对脂多糖、细菌和脂质的应答,以及对凋亡信号通路、血管形态形成等的调控。KEGG通路富集分析提示交集靶点主要涉及癌症相关通路、肿瘤坏死因子(TNF)信号通路、白细胞介素(IL)-17信号通路、丝裂原活化蛋白激酶(MAPK)通路和肝炎通路等。(3)柴胡的檞皮素、山奈酚和异鼠李素,以及黄芩的汉黄芩素和黄芩素为柴胡-黄芩治疗癌性发热的核心活性化学成分;前列腺素内过氧化物合成酶(PTGS)2、PTGS1、丝氨酸蛋白酶1(PRSS1)、Caspase-3、蛋白激酶Bα(AKT1)为治疗癌性发热的核心靶点;柴胡-黄芩药对主要通过癌症相关通路治疗癌性发热,同时也涉及肝炎通路、MAPK通路、TNF通路和IL-17通路。(4)分子对接技术结果显示,PRSS1、AKT1与檞皮素,AKT1与山奈酚,PTGS1Objective To explore the mechanism of Radix Bupleuri-Radix Scutellariae herb pair for the treatment of cancerous fever based on network pharmacology and molecular docking technique.Methods The active chemical components of Radix Bupleuri and Radix Scutellariae and their effect targets were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the targets related to cancerous fever were obtained from the databases of GeneCards,OMIM and TTD.The intersection on targets related to active chemical components of Radix Bupleuri and Radix Scutellariae with targets related to cancerous fever was obtained;in addition,for intersection targets,the protein-protein interaction network was constructed and the potential protein functional modules in the network were speculated by the STRING 11.0 database and CytoScape 3.7.2 software.The Gene Oncology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed based on Metascape platform.The CytoScape 3.7.2 software was used to construct drug components-intersection targets-pathway network,and the core active chemical components,core targets and core pathways of Radix Bupleuri-Radix Scutellariae herb pair for the treatment of cancerous fever were speculated according to topological parameters.The molecular docking was performed on aforesaid core active chemical components and core targets by AutoDock 1.5.6 software.Results(1)A total of 42 active chemical components and 178 effect targets of Radix Bupleuri-Radix Scutellariae herb pair were obtained,and there were 1562 targets related to cancerous fever and 98 intersection targets,as well as 2 potential protein functional modules.(2)The GO functional enrichment analysis indicated that intersection targets mainly concerned the responses to lipopolysaccharide,bacteria and lipid,as well as regulation on apoptotic signaling pathway and blood vessel morphogenesis,etc.The KEGG pathway enrichment analysis implied that interse

关 键 词：癌性发热 柴胡 黄芩 和解少阳法 网络药理学 分子对接技术 作用机制 

分 类 号：R730.6[医药卫生—肿瘤] R273[医药卫生—临床医学]