基于临床数据挖掘桥连网络药理学探究金银花—连翘药对治疗成人Still′s病的作用机制

Exploration of the mechanism of couplet medicines of Jinyinhua and Lianqiao in treating adult-onset Still′s disease based on clinical data mining and network pharmacology

目的:基于数据挖掘和网络药理学技术,分析中药治疗成人Still病(adult-onset Still′s disease,AOSD)的用药特点和规律,并阐明其核心药物组合治疗AOSD的分子机制。方法:运用IBM SPSS Modeler 18.0软件对中药处方进行关联规则分析,通过TCMSP数据库检索活性成分和药物靶点,在OMIM、GeneCard、DrugBank数据库中以“adultonset Still′s disease”或“AOSD”为关键词检索疾病靶点,运用Cytoscape 3.8.2软件构建“中药-活性成分-靶点”网络图;通过STRING数据库获得蛋白质互作网络,导入Cytoscape中获得核心靶点,并进行GO功能和KEGG通路富集分析;利用分子对接软件AutoDock对关键成分和核心靶点进行对接验证。结果:数据库中共筛选到28个完整处方,主要涉及89味中药;关联规则分析显示金银花-连翘是关联性最强的药对,这对核心药物共有27个活性成分,180个潜在作用靶点;金银花-连翘治疗AOSD的核心靶点有5个,包括肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-8(interleukin-8,IL-8/CXCL8)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1B(interleukin 1B,IL-1β)、肿瘤蛋白P53(tumor protein P53,TP53)。GO功能和KEGG通路富集分析结果显示IL-17、TNF和NF-κB等信号通路与金银花-连翘治疗AOSD密切相关。分子对接结果显示核心靶点和活性成分的对接活性好,其中木犀草素与TNF、贯叶连翘素与CXCL8具有较好的对接活性。结论:初步分析了安徽中医药大学第一附属医院风湿免疫科治疗AOSD的用药规律,并且在分子水平揭示了金银花-连翘核心药物组治疗AOSD的作用机制,为后续含金银花-连翘方剂治疗AOSD的开发提供了理论依据。

Objective:To analyze the medication characteristics and rules of traditional Chinese medicine in the treatment of adult-onset Still′s disease(AOSD)based on data mining and network pharmacology technology,and clarify the molecular mechanism of the core medicine combination in the treatment of AOSD.Methods:IBM SPSS Modeler 18.0 was used to analyze the association rules of prescriptions of traditional Chinese medicine.The active ingredients and drug targets were retrieved through the TCMSP database.The disease targets were searched with“adult-onset Still′s disease”or“AOSD”as keywords in OMIM,GeneCard and DrugBank databases,and the network map of“traditional Chinese medicines-active ingredients-targets”was constructed by Cytoscape 3.8.2 software.The protein interaction network was obtained by STRING database and imported into Cytoscape to obtain core targets,and then GO function and KEGG pathway enrichment analysis were performed.The molecular docking software AutoDock was used to verify the docking of key components and core targets.Results:A total of 28 complete prescriptions were screened in the database,mainly involving 89 Chinese herbs.Association rule analysis showed that Jinyinhua-Lianqiao was the most relevant drug pair,which had 27 active ingredients and 180 potential targets.There were five core targets for the treatment of AOSD by Jinyinhua-Lianqiao,including tumor necrosis factor(TNF),interleukin-8(IL-8/CXCL8),interleukin-6(IL-6),interleukin-1B(IL-1β),and tumor protein P53(TP53).GO function and KEGG pathway enrichment analysis showed that IL-17,TNF and NF-κB signaling pathways were closely related to the treatment of AOSD by Jinyinhua-Lianqiao.Molecular docking results showed that the core targets and active components had good docking activities,among which luteolin had good binding energy with TNF,and hypericum perforatum had good binding energy with CXCL8.Conclusion:In this paper,the medication rules of traditional Chinese medicine in the treatment of AOSD in Rheumatology and Immunology Department,The First Affiliated Hospital of Anhui University of Chinese Medicine are analyzed,and the mechanism of the Jinyinhua-Lianqiao core medicine group in the treatment of AOSD is revealed at the molecular level,which provide a theoretical basis for the subsequent development of Jinyinhua-Lianqiao formula for the treatment of AOSD.