基于网络药理学探讨大黄治疗急性胰腺炎的机制研究

Mechanism of Rhei Radix et Rhizoma in treatment of acute pancreatitis based on network pharmacology

目的 通过网络药理学方法探讨大黄在治疗急性胰腺炎(AP)中的潜在机制。方法 通过中药系统药理学数据库与分析平台(TCMSP)筛选大黄的活性成分,并进行大黄靶点的预测,使用Cytoscape软件构建大黄-活性成分-靶点网络图。通过Dis Ge NET、Gene Cards、OMIM数据库筛选AP的靶点,通过Venny 2.1.0制作大黄靶点和AP靶点的韦恩图,并得到共同靶点。构建共同靶点蛋白-蛋白互作(PPI)网络,使用DAVID数据库进行基因本体(GO)和基因组百科全书(KEGG)富集分析并将其可视化。取KEGG富集分析的前20条信号通路,构建信号通路与靶点之间的关系网络图。选择前5个活性成分和前10个靶点使用CB-Dock网站进行分子对接。结果 通过数据库筛选出16种大黄的活性成分、60个大黄靶点,2 024个AP靶点,31个共同靶点。其中,大黄的主要活性成分是β-谷甾醇、芦荟大黄素、泽兰黄醇、(-)-儿茶素、决明内酯等。大黄治疗AP的核心靶点包括TP53、TNF、MYC、CASP3、ESR1、IL1β、PTGS2、PPARG、CASP8、CASP9等。GO富集分析确定了264个与AP发生发展过程密切相关的条目。KEGG富集分析共确定了61条通路,其中排在首位的是P53信号通路。分子对接实验表明大黄的活性成分与其相应的靶点具有良好的结合亲和力。结论 大黄可以通过β-谷甾醇、芦荟大黄素、泽兰黄醇等主要活性成分作用于TP53、TNF、MYC、CASP3、ESR1等核心靶点治疗AP,其机制可能是通过P53信号通路、TNF信号通路等调控细胞凋亡和抑制炎症反应。

AIM To explore the potential mechanism of Rhei Radix et Rhizoma in the treatment of acute pancreatitis(AP)by network pharmacology.METHODS The active components of Rhei Radix et Rhizoma were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,and the targets of Rhei Radix et Rhizoma were predicted.Cytoscape software was used to construct Rhei Radix et Rhizoma-activecomponents-targets network diagram.The targets of AP were screened from the DisGeNET,GeneCards and OMIM database,and Venny 2.1.0 platform was used to make Venn diagram of Rhei Radix et Rhizoma targets and AP targets,and common targets were obtained.Protein-protein interaction(PPI)network was constructed for common targets,and GO and KEGG enrichment analyses were performed using the DAVID database,followed by visualization.The first 20 signal pathways of KEGG enrichment analysis were selected to construct the relationship network diagram between signal pathways and targets.Finally,the top 5 active components and the top 10 targets were selected for molecular docking using CB-Dock website.RESULTS Sixteen active components and 60 Rhei Radix et Rhizoma targets,2024 AP targets,and 31 common targets were obtained in the database.Among them,the main active components of Rhei Radix et Rhizoma were betasitosterol,aloe-emodin,eupatin,(-)-catechin,toralactone,etc.The core targets of Rhei Radix et Rhizoma for AP treatment included TP53,TNF,MYC,CASP3,ESR1,IL1β,PTGS2,PPARG,CASP8,CASP9,etc.GO enrichment analysis identified 264 items closely related to the occurrence and development of AP.KEGG enrichment analysis identified a total of 61 pathways,among which the P53 signaling pathway ranked first.Molecular docking experiments showed that the active components of Rhei Radix et Rhizoma had good binding affinity with their corresponding targets.CONCLUSION Rhei Radix et Rhizoma can treat AP by acting on TP53,TNF,MYC,CASP3,ESR1 and other core targets through betasitosterol,aloe-emodin,eupatin and other main active components.The mechanism may be to regulate apoptosis and inhibit inflammation through P53 signaling pathway and TNF signaling pathway.