基于网络药理学探究银杏叶治疗非动脉炎性前部缺血性视神经病变的机制  

Effect of Ginkgo biloba in the treatment of non-arteritic anterior ischemic optic neuropathy based on network pharmacology

作　　者：张梦 王欣玲[1] ZHANG Meng;WANG Xinling(The Fourth Affiliated Hosptial of China Medical University,Liaoning Key Laboratory of Lens,Shenyang 110005,Liaoning Province,China)

机构地区：[1]中国医科大学附属第四临床医院,辽宁省晶状体学重点实验室,辽宁省沈阳市110005

出　　处：《眼科新进展》2021年第11期1037-1042,共6页Recent Advances in Ophthalmology

基　　金：国家自然科学基金(编号81570838)。

摘　　要：目的基于网络药理学研究银杏叶相关药物成分治疗非动脉炎性前部缺血性视神经病变(NAION)的潜在生物学机制。方法利用传统中药网络数据库收集银杏叶的主要化学成分以及潜在的蛋白靶点,使用OMIM等数据库检索NAION疾病相关靶点。将上述靶点导入Venn软件获得二者的交集靶点。导入String数据库进行蛋白相互作用分析,并将数据结果导入Cytoscape-v3.8.2软件构建药材-化合物-靶点-通路网络图。利用Cytoscape-v3.8.2软件中插件筛选出核心靶点。运用David数据库进行生物富集以及信号通路转导分析,利用R语言对其进行可视化。利用分子对接软件进行分子对接模拟,验证药物和靶点分子连接程度。结果经筛选显示,银杏叶用于治疗的主要活性成分有20个,其主要为槲皮素、山奈酚、毛地黄黄酮,以及对应521个蛋白靶点,NAION的靶点有756个,二者交集靶点有26个。经过Cytoscape-v3.8.2软件中插件分别得到靶点数Hub集8个、MCC集12个、MCODE集24个,3个数据集的靶点取交集共筛选出8个核心靶点,分别为VEGFA、JUN、EGF、RELA、APP、ESR1、FOS、MYS。涉及通路有肿瘤通路、T细胞受体信号通路、PI3K-Akt信号通路、MAPK信号通路等,主要发挥抗炎、抗氧化、调节免疫以及神经保护等作用。结论基于网络药理学的综合分析,得到银杏叶有效成分治疗NAION的主要作用靶点及对应的信号通路,为后期实验验证提供了新的思路和生物信息学基础。Objective To study the potential biological mechanism of Ginkgo biloba extracts in the treatment of non-arteritic anterior ischemic optic neuropathy(NAION)based on network pharmacology.Methods The main chemical components and potential protein targets of Ginkgo biloba were collected from the traditional Chinese medicine database.Online Mendelian Inheritance in Man database was used to retrieve NAION-related targets.The above targets were imported into Venn software to obtain their intersection targets.The intersection targets were imported into the String database for protein interaction analysis.The results were imported into the Cytoscape-v3.8.2 software to construct a network diagram of herbs-compounds-targets-pathways.The core targets were screened out through the Cytoscape-v3.8.2 plug-in.David database was used for bio-enrichment and signal transduction analysis,and R language was used for visualization.Molecular docking simulation was carried out using molecular docking software to verify the molecular connection between drugs and targets.Results Ginkgo biloba has 20 major active components with therapeutic effects,including quercetin,kaempferol,and digicitrine,which correspond to 521 protein targets,756 NAION targets,and 26 intersection targets.Through the plug-in of Cytoscape-v3.8.2,8 Hub sets,12 MCC sets,and 24 MCODE sets were obtained,and 8 core targets were selected from the intersection targets of these three data sets,namely VEGFA,JUN,EGF,RELA,APP,ESR1,FOS,and MYS.The pathways involved were tumor pathway,T cell receptor signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,which play an important role in resisting inflammation and oxidation,regulating immunity,and protecting nerves.Conclusion Based on the comprehensive analysis of network pharmacology,the main targets and corresponding signal pathways of Ginkgo biloba’s active components in the treatment of NAION are obtained,providing a new idea and essential bioinformatics for later experimental verification.

关 键 词：银杏叶 非动脉炎性前部缺血性视神经病变 网络药理学 富集分析 

分 类 号：R774.6[医药卫生—眼科]