基于网络药理学探讨王氏保赤丸治疗功能性消化不良作用机制

Discussion on the Molecular Mechanism of Wangshi Baochi Pill in the Treatment of Functional Dyspepsia Based on Network Pharmacology

目的采用网络药理学研究王氏保赤丸治疗功能性消化不良的分子作用机制。方法通过TCMSP数据库筛选出王氏保赤丸的潜在活性成分(OB≥30%,DL≥0.18),并分别采用Uniprot数据库校正化合物靶点名称和Swiss Target Prediction数据库补充靶点信息;与GeneCards数据库获得的功能性消化不良(FD)疾病靶点相映射,得到王氏保赤丸治疗FD的潜在分子靶点。进一步使用Cytoscape软件系统构建“王氏保赤丸-活性化合物-潜在作用靶点”网络以及蛋白质相互作用网络,并使用R软件对王氏保赤丸的作用靶点进行GO生物功能分析和KEGG通路富集分析。结果经过分析得出:姜黄素、大黄素、槲皮素、β-谷甾醇、芦荟大黄素可能是王氏保赤丸治疗FD的主要活性成分。主要的潜在靶点网络包含210个靶点,关键靶点涉及PTGS2、AR、PTGS1、GR、ADRB2等。对潜在靶点进行GO功能富集分析涉及对氧化应激的反应、对营养水平的反应等生物学过程;RNA聚合酶II特异性等分子功能相关的过程。进行KEGG富集通路分析主要通路有雌激素信号通路、内分泌抵抗、NF-κB信号通路、cGMP信号通路、长期抑郁、胆碱能突触、钙信号通路、幽门螺杆菌感染中的上皮细胞信号传导等。结论王氏保赤丸可以通过多成分、多靶点、多途径共同发挥治疗功能性消化不良的作用。

Objective To explore the molecular mechanism of Wangshi Baochi pill in treating functional dyspepsia(FD)based on network pharmacology.Methods The potential active ingredients of Wangshi Baochi Pill(OB≥30%,DL≥0.18)were screened through the TCMSP database,and the target of the compounds were corrected and unified using the Uniprot database.In addition,Swiss Target Prediction database to supplement target information,which was mapped with the targets of FD from the GeneCards database to obtain the potential target of Wangshi Baochi Pill.Then,a“Wangshi Baochi Pill-active compound-potential target”network and protein interaction network were constructed by Cytoscape software.Finally,R software was used to perform GO biological function analysis and KEGG pathway enrichment analysis on the targets of Wangshi Baochi Pill.Results The analysis showed that curcumin,emodin,quercetin,β-sitosterol,and aloe-emodin might be the main active ingredients of Wangshi Baochi Pills for treating FD.The main potential target network contains 210 targets including PTGS2,AR,PTGS1,GR,ADRB2,and so on.GO function enrichment analysis of potential targets indicated several biological processes such as oxidative stress response and nutritional response,and molecular functions such as specificity of RNA polymerase II.The main pathways for KEGG enrichment pathway analysis are estrogen signal pathway,endocrine resistance,NF-κB signal pathway,cGMP signal pathway,chronic depression,cholinergic synapses,calcium signal pathway,and epithelial cell signaling in response to Helicobacter pylori infection.Conclusion Wangshi Baochi Pill can play a role in treating FD through multi-component,multi-target and multi-path mechanisms.