“肠粘连方”治疗新生儿肠道疾病活性成分及作用机制的网络药理学研究

Active components and mechanism of intestinal adhesion prescription for neonatal intestinal dis⁃eases based upon network pharmacology

目的分析“肠粘连方”治疗肠道疾病可能的活性成分,构建其“中药-成分-靶点”网络,探究其潜在作用机制。方法通过查阅文献、应用TCMSP数据库整理“肠粘连方”各中药的化学成分,再根据口服生物利用度(oral bioactivity,OB)和类药性(drug likeness,DL)筛选活性成分并整理各化学成分对应潜在靶点基因;通过GeneCards数据库整理肠粘连、肠梗阻、新生儿坏死性小肠结肠炎的疾病相关靶点基因;将各活性成分潜在靶点与疾病相关靶点基因进行比对分析,得到“肠粘连方”治疗新生儿肠道疾病的潜在靶点基因;使用Matascape数据库对筛选出的潜在靶点基因进行GO富集和KEGG通路注释;应用Cytoscape_v3.7.2构建”肠粘连方”治疗新生儿肠道疾病的“中药-成分-靶点”关系网络;利用PDB数据库、DiscoveryStudio、AutoDockTools、Pymol等软件对筛选出的部分活性成分与关键靶点进行分子对接。结果“肠粘连方”共含11味中药,合计120个非重复活性成分,与246个靶点基因存在潜在作用关系,其中与肠道疾病相关的靶点基因78个,影响了包括TNF signaling pathway、AGE-RAGE signaling pathway in diabetic complications、Pathways in cancer等24条信号通路;分子对接结果预测出了MOL000098、MOL000791与VCAM1、MAPK1最可能的结合位点。结论“肠粘连方”可通过多种活性成分抑制TNF等信号通路,抑制炎症进展,从而被应用新生儿肠粘连、肠梗阻的保守治疗。

Objective To explore the potential active components of intestinal adhesion prescription(IAP)and construct the“active components-targets-pathways”network of IAP and elucidate its potential mechanism.Methods The active components and related targets of IAP were searched from the database of TCMSP and literature reports.These active components were filtrated by oral bioactivity(OB)and drug likeness(DL).Then potential targets of IAP related to intestinal adhesion(IA),intestinal obstruction(IO)and necrotizing enterocolitis(NE)were searched from the database of GeneCards.The potential targets of IAP related to IA/IO/NE were obtained by aligning of two target lists mentioned above.GO enrichment and KEGG pathway of target genes were analyzed by the database of Matascape.Cytoscape_v3.7.2 software was utilized for constructing the“active components-targets-pathways”network of IAP related to these neonate intestinal diseases.Molecular docking hinted at the binding of active components and potential targets by using PDB,DiscoveryStudio,AutoDockTools and Pymol.Results IAP contained 11 traditional Chinese medicines and 120 active components,including 246 gene targets containing 78 targets related to IA/IO/NE and affecting many signaling pathways(e.g.TNF).Molecular docking revealed the interactions between potential targets(VCAM1&MAPK1)and selected active components(MOL000098&MOL000791).Conclusion Through suppressing the progression of inflammation through some signaling pathways,a large variety of active components of IAP may be used for treating neonatal intestinal adhesion,obstruction and necrotizing enterocolitis.