基于网络药理学探讨黄连对多囊卵巢综合征的作用机制

Study on the Mechanism of Rhizoma Coptidis on Polycystic Ovary Syndrome based on Network Pharmacology

目的:基于网络药理学方法,探讨中药黄连治疗多囊卵巢综合征的作用机制,阐述其科学内涵。方法:应用中药系统药理学平台(TCMSP)筛选黄连的有效活性成分与作用靶点;应用GeneCards、OMIM、PharmGkb数据库筛选多囊卵巢综合征的疾病靶点;应用R语言软件筛选药物与疾病共同靶点,应用Cytoscape软件构建药物-活性成分-疾病-靶点互作网络;应用STRING平台构建共同靶点蛋白互作网络(PPI);应用ClueGo插件对共同靶点进行基因功能(GO)分析,并应用R语言软件对共同靶点进行京都基因与基因组百科全书(KEGG)通路富集分析。结果:从TCMSP中获取黄连有效活性成分14种,靶点148个;从GeneCards数据库获取多囊卵巢综合征相关基因3517个;构建"药物-成分-疾病-靶点"网络,获得黄连治疗多囊卵巢综合征的关键靶点102个;构建其PPI网络,包含节点102个,边221条。通过分析PPI网络发现,黄连治疗多囊卵巢综合征的关键靶点包括JUN、丝裂原活化蛋白激酶(MAPK)、白细胞介素(IL)-6、重组人白介素8(CXCL8)、FOS、重组人白介素-1β(IL-1β)等。这些靶点主要涉及细胞凋亡、细胞因子活化、氧化剂抗氧化、一氧化氮代谢等生物学过程,并主要富集在晚期糖基化终产物及其受体(AGEs/RAGE)、肿瘤坏死因子(TNF)、白细胞介素17(IL-17)等信号通路上,其中AGEs/RAGE信号通路对多囊卵巢综合征的发生、发展有着关键性作用是公认的。结论:本研究初步验证了中药黄连治疗PCOS的基本药理学作用与机制,为进一步探究其作用机制奠定基础。

Objective:To explore the mechanism of Rhizoma Coptidis in the treatment of polycystic ovary syndrome and its scientific connotation based on network pharmacology.Methods:Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)was used to screen the active ingredients and targets in Rhizoma Coptidis;The target of polycystic ovary syndrome was screened by GeneCards,OMIM and PharmGkb databases;R language software was used to screen common targets of drugs and diseases.Drugs-active ingredients-diseases-targets interaction network was constructed by Cytoscape software;The common target protein interaction network(PPI)was constructed by STRING platform;Gene ontology(GO)analysis of common target was carried out by ClueGo plug-in,and the common targets were enriched by kyoto encyclopedia of genes and genomes(KEGG)pathway using R language software.Results:14 active ingredients of Rhizoma Coptidis and 148 targets were obtained from the TCMSP.3517 polycystic ovary syndrome related genes were obtained from the GeneCards database.The"drugs-ingredients-diseases-targets"network was constructed.102 key targets of ovarian syndrome were obtained;PPI network was constructed,including 102 nodes and 221 edges.By analyzing the PPI network,it was found that the key targets of Rhizoma Coptidis for the treatment of polycystic ovary syndrome included JUN,mitogen-activated protein kinase(MAPK),interleukin(IL)-6,recombinant human interleukin 8(CXCL8),FOS,recombination human interleukin-1β(IL-1β)and others.These targets were mainly involved in biological processes,such as apoptosis,cytokine activation,oxidant antioxidant,nitric oxide metabolism,and were mainly enriched in advanced glycation end products and their receptors(AGEs/RAGE),tumor necrosis factor(TNF),interleukin-17(IL-17)and other signaling pathways,in which the key role of AGEs/RAGE signaling pathway in the occurrence and development of polycystic ovary syndrome was recognized.Conclusion:This study preliminarily verifies the basic pharmacological effects and mechanisms of Chinese medicine Rhizoma Coptidis in the treatment of polycystic ovary syndrome,laying a foundation for further exploration of its mechanism of action.