基于网络药理学和分子对接技术探讨参苓白术散治疗抗生素相关性腹泻的分子作用机制  

A study on the molecular mechanism of Shenling Baizhu San in treating antibioticassociated diarrhea based on network pharmacology and molecular docking technology

作　　者：冯春驰 陈玩珊 刘盛国 谢守霞 FENG Chunchi

机构地区：[1]深圳市人民医院/暨南大学第二临床医学院/南方科技大学第一附属医院,广东深圳518020

出　　处：《中医临床研究》2023年第13期1-10,共10页Clinical Journal Of Chinese Medicine

基　　金：广东省深圳市临床药学重点学科(SZXK059)。

摘　　要：目的:运用网络药理学及分子对接技术探讨参苓白术散治疗抗生素相关性腹泻(Antibiotic-associated Diarrhea,AAD)可能的分子作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)获取参苓白术散的活性成分与药物作用靶点,在GeneCards和OMIM数据库中获取AAD的靶点。采用Cytoscape 3.6.0构建“中药-活性成分-参苓白术散”对AAD作用靶点的调控网络图,结合String数据库构建蛋白质-蛋白质相互作用网络,筛选出参苓白术散对AAD调控网络中潜在的最佳靶点。利用DAVID数据库进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。最后,运用AutoDock Tools 1.5.6和AutoDock Vina 1.0进行分子对接验证。结果:搜索得到参苓白术散活性化合物156个,对应的靶点276个;其中作用于AAD的靶点186个,AAD疾病靶点2787个。有GO条目440条与KEGG通路127条。参苓白术散的核心化合物木犀草素、槲皮素、山柰酚作用于关键靶蛋白JUN原癌基因(Jun Proto-oncogene,JUN)、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)等信号通路对AAD发挥整体疗效。参苓白术散关键活性成分与最佳核心靶蛋白的分子对接结合能基本低于-7 kJ/mol,证明参苓白术散关键活性成分与关键靶蛋白具有较好的结合活性。结论:本研究初步预测了参苓白术散治疗AAD的分子作用机制,为日后研究提供参照。Objective:The possible molecular mechanism of Shenling Baizhu San(参苓白术散)on antibiotic-associated diarrhee(AAD)is investigated by network pharmacology and molecular docking technology.Methods:The active ingredients and medicine targets of Shenling Baizhu San were obtained from TCMSP platform.The disease targets of AAD were obtained from GeneCards and OMIM databases.Cytoscape 3.6.0 software was used to construct the regulatory network diagram of TCM medicineactive ingredients-Shenling Baizhu San on AAD targets.The protein-protein interaction network was constructed by String database.The best potential targets of Shenling Baizhu San in AAD regulatory network were screened out.DAVID database was used for the GO function enrichment analysis and KEGG pathway enrichment analysis.At last,AutoDock Tools 1.5.6 and AutoDock Vina1.0 were used for the molecular docking verification.Results:A total of 156 active compounds and 276 corresponding targets were screened from Shenling Baizhu San.Among them,there were 186 targets acting on AAD and 2787 targets for AAD disease.There were 440 GO entries and 127 KEGG pathways.Luteolin,quercetin and kaempferol,the core compounds of Shenling Baizhu San,acted on key target proteins JUN,TP53 and other signal pathways,playing an overall effect on AAD.The molecular docking binding energy between the key active components of Shenling Baizhu San and the best core target protein was basically lower than-7 kJ/mol,which proved that the key active components of Shenling Baizhu San had good binding activity with the key target protein.Conclusion:This study preliminarily predicts the molecular mechanism of Shenling Baizhu San in the treatment of AAD,and provides a basis for further research.

关 键 词：参苓白术散 抗生素相关性腹泻 分子作用机制 网络药理学 分子对接技术 

分 类 号：R442.2[医药卫生—诊断学]