参苓白术散“异病同治”慢阻肺和菌群失调性腹泻作用机制的网络药理学分析

Network Pharmacological Analysis of the Mechanismof Shenling Baizhu Powder for"Different Disease with the Same Treatment"on COPD and Flora Imbalance Diarrhea

本研究基于网络药理学探讨参苓白术散“异病同治”慢阻肺和菌群失调性腹泻的主要活性成分、作用靶点及通路,明确其潜在作用机制。通过TCMSP或TCMID数据库筛选出参苓白术散的活性成分及作用靶点;运用GeneCards和OMIM-genemap获取与慢阻肺与菌群失调性腹泻发生、发展相关的靶点,得到参苓白术散慢阻肺菌群失调性腹泻交集靶点;利用STRING数据库绘制蛋白相互作用网络并进行拓扑分析,对其进行GO功能及KEGG通路富集分析;利用Cytoscape 3.9.1软件构建药物活性成分疾病靶点通路作用网络。通过SYBYL等软件进行主要活性成分与关键靶点的分子对接,共获得参苓白术散组方靶点441个,慢阻肺与菌群失调性腹泻的共同靶标133个;药物与疾病交集靶点39个,获得了PTGS2、NOS2、JUN、RELA和TNF等关键靶点;富集分析结果显示,参苓白术散可能参与炎症反应、对外源性刺激的反应、对脂多糖的反应、对细菌来源分子的反应等生物学进程,调控AGE-RAGE信号通路和IL-17信号通路等,参与慢阻肺和菌群失调性腹泻的治疗过程。分子对接结果显示,关键靶点与相关活性成分之间具有较高的结合活性。参苓白术散对慢阻肺和菌群失调性腹泻作用具有多成分、多靶点、多通路的作用机制特点,可为参苓白术散的临床用药提供理论基础。

Based on network pharmacology,explore the main active components,targets and pathways of Shenling Baizhu Powder"different disease with the same treatment"COPDand flora imbalance diarrhea and clarify its potentialmechanism.The active components and targets of Shenling Baizhu Powder were screened by TCMSP or TCMID.GeneCards and OMIM-Genemap were used to obtain the targets related to the occurrence and development of COPD and flora imbalance diarrhea,and the intersection targets of"Shenling Baizhu Powder-COPD-flora imbalance diarrhea"were obtained.They were uploaded to the STRING database to draw the protein interaction network and conduct topological analysis,and analyzed the GO function and KEGG pathway enrichment.By using Cytoscape 3.9.1 the active ingredient-target-pathway action network was constructed.The molecular docking of main active components and key targets was carried out by using SYBYL and others.A total of 441 targets of Shenling Baizhu Powder and 133 common targets of COPD and flora imbalance diarrhea were obtained;There were 39 intersection targets between drugs and diseases,and key targets such as PTGS2,NOS2,JUN,RELA,TNF were obtained;The results of enrichment analysis showed that Shenling Baizhu Powder may participate in biological processes such as inflammatory response,response to xenobiotic stimulus,response to lipopolysaccharide and response to molecule of bacterial origin,regulate AGE-RAGEsignaling pathway and IL-17 signaling pathway to treat COPDand flora imbalance diarrhea.Molecular docking results showed that the key targets had high binding activity with related active components.The effect of Shenling Baizhu Powder on COPD and flora imbalance diarrhea has the characteristics of multi-component,multi-target and multi-channel mechanism,which can provide a basis for the clinical use of Shenling Baizhu powder.