基于网络药理学与分子对接技术探讨红花治疗视网膜静脉阻塞的作用机制研究

Study on the mechanism of Carthami Flos in treating retinal vein occlusion based on network pharmacology and molecular docking technology

本文旨在通过网络药理学和分子对接技术探讨红花治疗视网膜静脉阻塞(RVO)的分子作用机制。首先,通过中药系统药理学数据库与分析平台(TCMSP)获取红花的活性成分和潜在作用靶点。然后,利用GeneCards数据库和OMIM数据库收集RVO相关疾病靶点,借助R 3.6.3软件运行R语言获取红花-RVO交集靶点数据集,通过FunRich 3.1.3软件绘制Venn图和Cytoscape 3.7.0软件构建疾病-成分-靶点网络。利用String数据库和Cytoscape 3.7.0软件绘制蛋白互作(PPI)网络。利用Metascape数据库进行GO和KEGG富集分析。最后,利用AutoDock Vina 1.1.2软件对红花主要活性成分与对应关键靶点进行分子对接验证。本研究共筛选得到红花22个活性成分、186个潜在作用靶点及1842个RVO相关疾病靶点,最终得到128个红花-RVO交集靶点。PPI网络分析表明,AKT1、JUN、IL6、MAPK1、MAPK8、EGF、CXCL8、MMP9等可能是治疗RVO的核心靶点。GO富集分析,共得到生物过程(BP)条目2000个,分子功能(MF)条目174个,细胞成分(CC)条目108个;KEGG富集分析,共筛选得到167条信号通路。分子对接结果提示,槲皮素、木犀草素、山柰酚等与AKT1、IL6、MAPK1、MAPK8、VEGFA等关键靶点有着较好的结合活性。槲皮素、木犀草素、黄芩素、β-谷甾醇等化合物可能是治疗RVO的物质基础,通过作用于AKT1、IL6、VEGFA、MAPK1、MAPK8、JUN等关键靶点,同时调控PI3K/Akt信号通路、IL-17信号通路、NF-κB信号通路、VEGF信号通路等多种信号途径,从而发挥抑制炎性反应、抗氧化应激及调节免疫等作用。

To explore the molecular mechanism of Carthami Flos in the treatment of retinal vein occlusion by network pharmacology and molecular docking technology.First,the active components and potential targets of Carthami Flos were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Then,disease targets associated with retinal vein occlusion(RVO)were collected through the GeneCards database and the OMIM database.Carthami Flos-RVO intersection target datasets were obtained by running R language using R 3.6.3 software.Venn diagrams were drawn using FunRich 3.1.3 software and Cytoscape 3.7.0 software was used to construct disease-component-target networks.Protein interaction(PPI)networks were drawn using the String database and Cytoscape 3.7.0 software.GO and KEGG enrichment analyses were performed using the Metascape database.Finally,Molecular docking validation of the main active components of Carthami Flos and the corresponding key targets was performed by AutoDock Vina 1.1.2 software.In this study,a total of 22 active components,186 potential targets and 1842 RVO-related disease targets of Carthami Flos were screened.Eventually,128 intersection targets were obtained.PPI network analysis indicated that AKT1,JUN,IL6,MAPK1,MAPK8,EGF,CXCL8,and MMP9 may be core targets for the treatment of RVO.A total of 2000 biological process(BP)entries,174 molecular function(MF)entries,and 108 cellular component(CC)entries were obtained by GO enrichment analysis.A total of 167 signaling pathways were screened by KEGG enrichment analysis.Molecular docking results suggested that quercetin,luteolin,and kaempferol had good binding activity to key targets such as AKT1,IL6,MAPK1,MAPK8,and VEGFA.quercetin,luteolin,baicalein,β-sitosterol and other compounds may be the material basis for the treatment of RVO.These compounds may act on key targets,such as AKT1,IL6,VEGFA,MAPK1,MAPK8,and JUN.At the same time,it plays a role in inhibiting inflammatory response,anti-oxidative stress and regulating immunity by regulating a variety of signaling pathways,such as PI3K/Akt signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,and VEGF signaling pathway.