基于网络药理学和分子对接技术分析石榴皮治疗溃疡性结肠炎作用机制  

Analysis of mechanism of action of pomegranate peel in the treatment of ulcerative colitis based on network pharmacology and molecular docking

作　　者：徐千 佟瑶[2] 陈瑞超 Xu Qian;Tong Yao;Chen Ruichao(Graduate School of Anhui University of Chinese Medicine,Hefei Anhui 230012;Department of Anorectum of Xuzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Xuzhou Jiangsu 221003)

机构地区：[1]安徽中医药大学研究生学院,安徽合肥230012 [2]南京中医药大学附属徐州市中医院肛肠科,江苏徐州221003

出　　处：《山西中医药大学学报》2024年第3期296-304,共9页Journal of Shanxi University of Chinese Medicine

基　　金：徐州市中医药科技发展计划项目(XZYB2021004)。

摘　　要：目的:基于网络药理学方法和分子对接技术探究石榴皮治疗溃疡性结肠炎(UC)的活性成分、关键靶点和潜在的药理学机制。方法:从TCMSP数据库、Swiss ADME数据库及SwissTargetPrediction数据库筛选活性成分及靶点信息,通过UniProt数据库筛选出人类靶点并规范基因名;再从GeneCards数据库、DisGeNET数据库筛选疾病靶点,应用Venny2.1软件将石榴皮与UC靶点基因取交集生成韦恩图;使用Cytoscape 3.9.1软件作药物-活性成分-靶点-疾病网络图并筛选出主要活性成分;利用STRING数据库构建主要成分靶点互作网络并筛选关键靶点;然后导入Cytoscape 3.9.1软件构建PPI网络图;随后用Metascape数据库进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析(P<0.01)。最后,进行分子对接,以预测活性成分与核心靶点的结合。结果:共筛选出7种石榴皮活性成分和124个石榴皮抗溃疡性结肠炎(PP-UC)相关靶点。槲皮素、木犀草素和山奈酚可能是潜在的主要活性成分,酪氨酸蛋白激酶(SRC)可能成为潜在的治疗靶点。GO功能分析靶基因主要富集于受体复合物、蛋白激酶复合物、膜筏、中心体等。KEGG分析石榴皮治疗UC的通路可能为PI3K-Akt信号通路、花生四烯酸代谢通路、AMPK通路等。分子对接结果表明木犀草素、山奈酚和槲皮素分别与SRC结合良好。结论:石榴皮可能通过调节炎性因子,改善肠上皮屏障等多种机制发挥抗UC的作用,PI3K-Akt信号通路、花生四烯酸代谢通路、AMPK通路可能是重要的调节通路。Objective:To investigate the active ingredients,key targets and potential pharmacological mechanisms of pomegranate peel in the treatment of ulcerative colitis(UC)based on network pharmacological methods and molecular docking techniques.Methods:Active ingredients and target information were screened from TCMSP database,Swiss ADME database and SwissTargetPrediction database,and human targets were screened from UniProt database and gene names were standardized.Then,disease targets were screened from GeneCards database and DisGeNET database,and Venny2.1 software was used to generate Venn diagram by intersection of pomegranate peel and UC target genes.Cytoscape 3.9.1 software was used to construct the drug-active ingredient-target-disease network and screen the major active ingredients.The STRING database was used to construct the main component-target interaction network and screen the key targets.Then Cytoscape 3.9.1 software was imported to construct the PPI network diagram.Subsequently,gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using Metascape database(P<0.01).Finally,molecular docking was performed to predict the binding of the active ingredients to the core targets.Results:A total of 7 active ingredients of pomegranate peel and 124 anti-ulcerative colitis(PP-UC)related targets were screened.Quercetin,luteolin and kaempferol might be the main potential active ingredients,and tyrosine protein kinase(SRC)might be a potential therapeutic target.GO function analysis showed that target genes were mainly enriched in receptor complex,protein kinase complex,membrane raft,centrosome,etc.KEGG analysis showed that the pathways of pomegranate peel in the treatment of UC might be PI3K-Akt signaling pathway,arachidonic acid metabolism pathway,AMPK pathway,etc.Molecular docking results showed that luteolin,kaempferol and quercetin bound well to SRC,respectively.Conclusion:Pomegranate peel may play a role in anti-UC by regulating in

关 键 词：溃疡性结肠炎 石榴皮 网络药理学 分子对接 SRC 

分 类 号：R285.5[医药卫生—中药学]