| 王海霞,康显杰,朱燕,等.基于网络药理学和分子对接技术探讨白术治疗溃疡性结肠炎的潜在分子机制[J].浙江中医药大学学报,2020,44(9):916-923, 928. |
| 基于网络药理学和分子对接技术探讨白术治疗溃疡性结肠炎的潜在分子机制 |
| Potential Molecular Mechanism of Atractylodes Macrocephala in the Treatment of Ulcerative Colitis Based on Network Pharmacology |
| DOI：10.16466/j.issn1005-5509.2020.09.019 |
| 中文关键词: 白术 网络药理学 分子对接 溃疡性结肠炎 白术内酯 芹菜素 木犀草素 p53蛋白 |
| 英文关键词: Atractylodes macrocephala network pharmacology molecular docking ulcerative colitis atractylenolide apigenin luteolin p53 protein |
| 基金项目:浙江省基础公益研究计划项目(LGC20H280002) |
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| 中文摘要: |
| [目的]通过网络药理学方法探讨白术治疗溃疡性结肠炎(ulcerative colitis，UC)的潜在分子生物学机制。[方法]从中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database，TCMSP)等数据库及Pubmed文献数据库中检索并获取与白术相关的活性成分及潜在作用靶点，构建白术活性成分-潜在靶点网络；通过DisGeNET、药物靶标数据库(Therapeutic Target Database，TTD)、GeneCards数据库筛选与UC相关的靶点，利用Venny 2.1软件绘制韦恩图并获取药物及疾病共有靶点；通过Cytoscape软件BisoGenet插件分析得到蛋白互作网络及核心靶点，进一步对核心靶点进行网络拓扑分析，利用DAVID数据库对核心靶点进行富集分析，获得白术治疗UC的潜在基因本体(gene ontology，GO)生物进程及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)信号通路。[结果]通过SwissADME数据库，评价各分子结构是否满足Lipinski、Ghose等类药规则，筛选得到白术活性成分11种，白术活性成分主要有白术内酯Ⅰ、Ⅱ、Ⅲ、木犀草素、芹菜素等。由TCMSP、Swiss TargetPrediction数据库筛选出白术活性成分的潜在作用靶点144个，DisGeNET、TTD、GeneCards数据库筛选获得UC相关靶点147个。根据度值(degree)筛选得出白术治疗UC的核心靶点58个，主要涉及p53蛋白、神经生长因子受体酪氨酸激酶A(tyrosine kinase A，TrkA)、雌激素受体1(estrogen receptor 1，ESR1)、微小染色体维持蛋白2(microchromosomal maintenance protein 2，MCM2)等。设定错误发生率(false discovery rate，FDR)≤0.05，通过GO生物进程富集分析确定了30个条目，主要包括基因沉默调控、端粒组织、DNA复制依赖性核小体组装、rDNA染色质沉默等。KEGG通路富集结果显示白术治疗UC的潜在通路共48条，主要涉及癌症中的转录失调通路、癌症通路、前列腺癌通路、细胞周期通路等。分子对接结果显示，白术活性成分木犀草素、芹菜素与多个疾病核心靶点蛋白存在潜在结合位点。[结论]白术治疗UC是多成分、多靶点、多途径共同作用的结果，本研究结果为白术的临床应用以及UC相关疾病的基础及临床研究提供了科学依据，同时为新药的研发及应用提供了新思路。 |
| 英文摘要: |
| [Objective]To explore the potential molecular biological mechanism of Atractylodes macrocephala in the treatment of ulcerative colitis(UC) based on network pharmacology.[Methods]The active components and potential targets related to Atractylodes macrocephala were selected from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and literature search， and the network of active components and potential targets of Atractylodes macrocephala was constructed. The targets related to UC were selected by DisGeNET， Therapeutic Target Database(TTD) and GeneCards database， and Wayne map was drawn by Venny 2.1 software to obtain common targets of drugs and diseases. Through the analysis of biosogenet plug-in， the protein-protein interaction(PPI) network， the core target were obtained. The network topology of the core target was furtherly analyzed. The core target was enriched and analyzed with DAVID database to obtain the potential gene ontology(GO) biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway of Atractylodes macrocephala in the treatment of UC.[Results]According to the Swiss ADME database and the evaluation of molecular structure whether it meets the Lipinski， Ghose and other drug rules， 11 kinds of active compounds of Atractylodes macrocephala were screened. The main active components of Atractylodes macrocephala were lipoid Ⅰ， Ⅱ， Ⅲ， luteolin， apigenin， etc.， and 144 potential targets of Atractylodes macrocephala were screened by TCMSP and Swiss Target Prediction database， and 147 UC related targets were screened by DisGeNET， TTD and GeneCards database. According to the degree value， 58 core targets of Atractylodes macrocephala intervention on UC were selected， including tumor antigen p53， tyrosine kinase A(TrkA)， microchromosomal maintenance protein 2(MCM2)， etc. According to the false discovery rate(FDR)≤0.05， the enrichment analysis of GO biological process identified 30 items， including regulation of gene silencing， telomere organization， DNA replication-dependent nucleosome assembly， chromatin silencing at rDNA， etc. The results of KEGG pathway enrichment showed that there were 48 potential pathways for Atractylodes macrocephala in the treatment of UC， mainly involving transcriptional misregulation in cancer， pathways in cancer， prostate cancer， cell cycle， etc. The results of molecular docking showed that luteolin and apigenin， the active components of Atractylodes macrocephala， had potential binding sites with several disease core target proteins.[Conclusion]The treatment of UC with Atractylodes macrocephala is the result of multi-component， multi-target and multi-channel interaction Results of this reseairch provide scientific basis for the clinical application of Atractylodes macrocephala and the basic and clinical research of UC related diseases， as well as new ideas for the development and application of new drugs. |
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