基于网络药理学探讨黄芪增液汤治疗慢传输型便秘的作用机制

Discussion on the mechanism of Huangqi Zengye decoction in treating slow transit constipation based on network pharmacology

目的基于网络药理学的方法探讨黄芪增液汤治疗慢传输型便秘(STC)的药效作用机制。方法利用中药系统药理学数据库分析平台(TCMSP)数据库查询8味中药活性化学成分及相关靶点信息,Uniprot数据库使靶蛋白信息标准化,Cytoscape3.7.2软件构建中药-成分-靶点网络图,GeneCards数据库找到STC相关治疗靶点,Venny平台查找交集靶点,STRING数据库获得蛋白相互作用关系并进行蛋白质-蛋白质相互作用(PPI)网络分析;应用DAVID数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,通过R软件对富集结果进行生物功能的可视化分析。结果黄芪增液汤筛选得到60个活性化学成分,靶点蛋白846个,与STC相关靶点蛋白111个,构建核心网络2个;通过GO富集分析发现,P<0.01的共211条,黄芪增液汤治疗STC涉及的靶点通路包括RNA聚合酶Ⅱ启动子转录的正调控、细胞质膜、蛋白结合等;KEGG富集分析结果发现83个富集条目,黄芪增液汤治疗STC的机制可能与癌症通路、磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶(PI3K/AKT)信号通路、神经活性配体-受体相互作用、肿瘤坏死因子信号通路、丙型肝炎、环磷酸腺苷(cAMP)信号通路等相关通路条目有关。分子对接结果表明,3种核心化合物与STC相关靶点转录后基因沉默(PTGS)蛋白具有较好的结合活性。结论黄芪增液汤中有效活性成分3β-乙酰氧基苍术酮、β-谷甾醇、花生四烯酸、木犀草素等可能是通过cAMP、PI3K/AKT、肿瘤坏死因子等信号通路而发挥治疗STC的作用。

Objective To explore the mechanism of pharmacodynamic action of Huangqi Zengye decoction in treating slow transit constipation(STC)based on network pharmacology.Methods Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)database was used to query the active chemical components of 8 traditional Chinese medicines and related target information,Uniprot database was used to standardize the target protein information,Cytoscape3.7.2 software was used to construct Chinese medicine-ingredient-target network map,GeneCards database was used to find STC-related therapeutic targets,Venny platform was used to find the intersection targets,and STRING database was used to obtain protein interaction and protein-protein interaction(PPI)network analysis;DAVID database was used for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis,and R software was used to visualize the biological function of the enrichment results.Results Sixty active chemical components were screened by Huangqi Zengye decoction,including 846 target proteins and 111 target proteins related to STC,and 2 core networks were constructed;the GO enrichment analysis found that there were 211 entries with P<0.01,and the target pathways involved in the treatment of STC with Huangqi Zengye decoction including the positive regulation of transcription of RNA polymeraseⅡpromoter,cytoplasmic membrane,protein binding,and so on;the KEGG enrichment analysis found 83 enriched entries,and the mechanism of Huangqi Zengye decoction in treating STC may be related to the pathways in cancer,phosphatei-dylinositol 3 kinase/serine-threonine kinase(PI3K/AKT)signaling pathway,neuroactive ligand-receptor interaction,tumor necrosis factor signaling pathway,hepatitis C,cyclic adenosine 3',5'-monophosphate(cAMP)signaling pathway,and other related pathway entries.The molecular docking results indicated that the three core compounds had good binding activity with the STC related target post-transcriptional gene silencing(PTGS)protein.Conclusion The active ingredients 3β-acetoxyatractylone,beta-sitosterol,arachidonic acid and luteolin in Huangqi Zengye decoction may play a role in the treatment of STC through cAMP,PI3K/AKT,tumor necrosis factor and other signaling pathways.