附子理中丸治疗肠结核作用机制的网络药理学研究

Network pharmacology based research of mechanism of Fuzi Lizhong pills for treatment of intestinal tuberculosis

背景临床上常规结核化疗方案治疗肠结核副作用较大.附子理中丸是一种传统的治疗肠结核的中药.研究其具体的生物学作用机制有助于肠结核的治疗的进一步研究.目的基于网络药理学研究附子理中丸治疗肠结核的作用机制.方法在TCMSP数据库中分别筛选附子理中丸5种主要药材的有效活性成分,并从TCMSP及Drugbank数据库中收集有效成分的作用靶点;在Genecards数据库收集肠结核相关的疾病靶点;通过Venny 2.1.0在线网站取药物活性成分作用靶点与疾病靶点的重叠靶点作为药物治疗肠结核的潜在治疗靶点;使用Cytoscape 3.9.1软件构建“药物-活性成分-靶点-疾病”网络;在String在线数据库中构建药物潜在治疗靶点的蛋白质互作(protein-protein interaction,PPI)网络,并通过Cytoscape 3.9.1软件进行拓扑学及可视化分析,进一步选取核心作用靶点;使用R4.1.2软件中的“clusterProfiler”程序包对潜在药物作用靶点进行京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析和基因本体论(Gene Ontology,GO)分析.结果从公共数据库中一共收集了附子理中丸活性药物成分共108种,药物作用靶点254个,疾病靶点2579个;筛选出的药物潜在治疗靶点一共134个,核心靶点10个(AKT1、IL-6、TP53、VEGFA、IL1B、JUN、CASP3、PTGS2、PPARG、MAPK3);GO和KEGG富集分析提示附子理中丸治疗肠结核的生物学机制可能与细胞氧化应激、细胞因子参与的免疫调节相关,可能参与的功能通路包括白介素17信号通路、氧化应激通路等.结论附子理中丸治疗肠结核的作用机制与氧化应激、细胞因子参与的炎症或免疫调节相关,为日后的临床或基础研究提供了研究方向.

BACKGROUND Conventional tuberculosis chemotherapy regimens used in clinical practice have significant side effects when treating intestinal tuberculosis(ITB).Fuzi Lizhong pills are a traditional Chinese medicine commonly used to treat ITB.Studying its exact mechanism of action can help further the research on the treatment of ITB.AIM To study the mechanism of Fuzi Lizhong pills for treatment of ITB based on network pharmacology.METHODS The active components of five main medicinal materials of Fuzi Lizhong pills were screened from the TCMSP database,and the effective component-related targets were collected from the TCMSP and Drugbank databases.The targets related to ITB were collected from the Genecards database.Through the Venny2.1.0 online website,the overlapping targets of drug active components and disease targets were selected as potential therapeutic targets for the treatment of ITB.Cytoscape3.9.1 software was used to construct a network of“drug-active ingredients-targets-disease”.The protein-protein interaction(PPI)network of drug potential therapeutic targets was constructed in the online database String.Then,the topology and visualization were analyzed with Cytoscape3.9.1 software,and the core targets were further selected.The potential therapeutic targets were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses using the“clusterProfiler”package in R 4.1.2.RESULTS A total of 108 active drug components of Fuzi Lizhong pills,254 drug action targets,and 2579 disease targets were screened from the public database.A total of 134 potential therapeutic targets and 10 core targets(AKT1,IL-6,TP53,VEGFA,IL1B,JUN,CASP3,PTGS2,PPARG,and MAPK3)were selected.GO and KEGG enrichment analyses suggested that the biological mechanism of Fuzi Lizhong pills for the treatment of ITB may be related to cellular oxidative stress,immune regulation involving cytokines,and functional pathways including the IL-17 signal pathway,oxidative stress pathway,and so on.CONCLUSION The mechanism of Fuzi Lizhong pills for treatment of ITB is related to oxidative stress and immune regulation of cytokines.