基于网络药理学探讨李氏溃结方治疗溃疡性结肠炎的分子机制

Exploration of the molecular mechanism of Lishi-Kuijie decoction in the treatment of ulcerative colitis based on network pharmacology

利用网络药理学及分子对接方法探究李氏溃结方治疗溃疡性结肠炎(ulcerative colitis,UC)分子机制。从中药系统药理学分析平台TCMSP挖掘李氏溃结方中13味中药相关的化学成分和作用靶点;通过OMIM数据库、DisGeNet数据库及GeneCards数据库筛选UC的预测靶点。利用Cytoseape 3.7.2软件构建药物-成分-疾病-靶点网络;基于String数据库,构建李氏溃结方治疗UC靶点互作网络,根据拓扑学参数筛选李氏溃结方治疗UC的核心靶点。利用R包clusterprofile对交集基因进行转换,对疾病与药物交集靶点进行GO生物学过程富集分析和KEGG通路注释分析。结果发现,李氏溃结方化合物-UC-靶点网络包含149个化合物和相应靶点108个,核心靶点涉及信号转导与转录激活因子3、白介素6、肿瘤坏死因子、C-X-C趋化因子配体8、白介素2等。GO功能富集分析得到2371个GO条目;KEGG富集筛选得到155条通路,主要涉及炎症性肠病信号通路、PI3K-AKT信号通路、NF-κB信号通路、TNF信号通路、Toll样受体信号通路等。结果显示:关键药效分子与核心靶点均能稳定结合,其中与IL2、TNF-α、MAPK1、RELA结合能更低。本工作预测了李氏溃结方治疗UC疾病的可能作用机制,为进一步寻找其有效成分和作用机制奠定基础。

We used network pharmacology and molecular docking to investigate the molecular mechanism of Lishi-Kuijie decoction(KJF)in the treatment of ulcerative colitis(UC).Chemical components and targets related to the 13 herbs of Chinese Materia Medical in KJF were searched through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The UC-related targets were identified through OMIM,DisGeNet and GeneCards databases.Using Cytoscape 3.7.2 software a drug-compound-disease-target network was established.The target interaction network and core target for KJF against UC was built and selected based on the String database and topological parameters.Using the R package clusterprofile in Bioconductor,the intersection genes and the disease-drug intersection targets were transformed to Entrez gene ID,followed by gene ontology biological process enrichment analysis and KEGG pathway annotation analysis.The KJF compound-UC target network contained 149 compounds,108 corresponding targets and 12 core targets(including signal transducer and activator of transcription 3,interleukin 6,tumor necrosis factor,c-x-c motif chemokine ligand 8,interleukin 2,etc.).We identified 2371 GO terms and 155 pathways(mainly involving IBD,PI3 K-ATK,NF-kappa B,TNF,Tolllike receptor signaling pathway)as determined by enrichment analysis.Molecular docking,used with the key molecular factors and the core targets,revealed stable binding for IL2,TNF-α,MAPK1 and RELA.These results suggest the possible molecular mechanism of KJF in treatment of UC and lay the foundation for further characterization of the components and their mechanisms.