目的:采用网络药理学方法研究苏杏痰咳合剂治疗慢性阻塞性肺疾病急性加重期(Acute Exacerbation of Chronic ObstructivePulmonaryDisease,AECOPD)的主要活性成分与作用机制.方法:通过中药系统药理学数据库与分析平台(TCMSP)检索苏杏痰咳合剂组方中药物的主要活性成分及其作用靶点,应用GeneCards、OMIM、TTD、DrugBank数据库检索AECOPD治疗靶点,运用Venny 2.1工具获取活性成分与治疗AECOPD的交集靶点,利用STRING平台进行蛋白质-蛋白质相互作用分析并获取核心靶点,运用Cytoscape 3.8.2软件构建中药-活性成分-靶点-疾病网络图及蛋白质-蛋白质相互作用网络图,通过MetaScape数据库对核心靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最后将网络中度值较高的10种活性成分与核心靶点利用AutoDock 4.2.6软件进行分子对接.结果:筛选出苏杏痰咳合剂主要活性成分227个、作用靶点243个,以及AECOPD靶点3 242个,二者的交集靶点有186个.对交集靶点进行蛋白质-蛋白质相互作用分析,发现肿瘤蛋白P53(Tumor Protein P53,TP53)、JUN原癌基因(Jun Proto-oncogene,JUN)、α-丝氨酸/苏氨酸蛋白激酶(RAC-alpha Serine/Threonine-protein Kinase,AKT1)、信号转导因子和转录激活因子 3(Signal Transducer and Activator of Transcription 3,STAT3)为苏杏痰咳合剂治疗AECOPD的核心靶点.核心靶点GO功能富集和KEGG通路富集分析结果提示苏杏痰咳合剂发挥治疗AECOPD作用的机制与药物化学反应、氧化反应、DNA结合转录等生物学过程以及晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)、癌症、炎症等信号通路有关.分子对接结果显示各活性成分与核心靶点均可进行自发结合.结论:苏杏痰咳合剂通过多成分、多靶点、多通路发挥治疗AECOPD的作用,作用机制可能与通过TP53、JUN、AKT1、STAT3等靶点干预AGE-RAGE、癌症、炎症等信号通路有关.
A network pharmacology study on treating acute exacerbation of chronic obstructive pulmonary disease with the Suxing Tanke mixture
Objective:To study the main active ingredients and action mechanism of the Suxing Tanke mixture(苏杏痰咳合剂)in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)by network pharmacology.Methods:The main active constituents of the Suxing Tanke mixture and their corresponding targets were retrieved from TCMSP.GeneCards,OMIM,TTD and DrugBank databases were used to retrieve the therapeutic targets of AECOPD.The intersection targets of active ingredients and AECOPD were obtained by Venny 2.1 tool.The intersection genes were imported into the STRING database to obtain a protein-protein interaction network and core targets.Cytoscape 3.8.2 software was used to construct Chinese medicine-active ingredient-target-disease network diagram and protein-protein interaction network diagram.GO functional enrichment analysis and KEGG pathway enrichment analysis were performed on the core targets by MetaScape database.Finally,the 10 active ingredients with high degree values were linked to the core target by AutoDock 4.2.6 software for molecular docking.Results:A total of 227 main active ingredients with 243 corresponding targets were screened out from the Suxing Tanke mixture.There were 3 242 targets related to the treatment of AECOPD,and 186 intersecting targets of the prescription and the disease.The protein-protein interaction analysis of intersection targets showed that TP53,JUN,AKT1,STAT3 were the core targets of the Suxing Tanke mixture in the treatment of AECOPD.The GO function enrichment analysis and KEGG pathway enrichment analysis of the core targets revealed that the action mechanism of the Suxing Tanke mixture on AECOPD was associated with biological processes such as medicinal chemical reaction,oxidation reaction,DNA-binding transcription,and signal pathways such as AGE-RAGE,cancer and inflammation.The molecular docking results showed that all active ingredients can spontaneously bind to the core target.Conclusion:The Suxing Tanke mixture can treat AECOPD through multi-component,multi-target,and multi-pathway,and the action mechanism may be related to the intervention on AGE-RAGE,cancer,inflammation and other signaling pathways through TP53,JUN,AKT1,STAT3 and other targets.
The Suxing Tanke mixtureAcute exacerbation of chronic obstructive pulmonary diseaseNetwork pharmacologyAction mechanism
万方数据
维普
