摘要
目的:采用网络药理学与分子对接的方法探索牛蒡子治疗糖尿病肾病的潜在活性成分及相关作用机制。方法:通过中药系统药理学数据库分析平台(TCMSP)数据库搜集牛蒡子的活性成分、靶点及二维结构图;在TTD数据库、Drugbank数据库、GeneCards数据库与OMIM数据库获取糖尿病肾病疾病相关靶点,剔除重复的疾病靶标,再结合Uniprot数据库确定各靶点的Uniprot ID。以String数据库的数据为基础,利用Cytoscape 3.7.0软件中的Network Analyzer和cytoHubbart插件对PPI网络计算拓扑结构值,建立重要靶点的拓普网络关系图;绘制“活性成分-靶点-通路”网络图;核心靶点导入Metascape数据库,进行GO生物过程富集分析和KEGG分析;从RSCB数据库下载关键靶蛋白的晶体结构,运用AutoDock进行对接,采用Pymol软件进行可视化处理。结果:牛蒡子有8个活性成分,80个主要靶点,与糖尿病肾病疾病靶点取交集后获得靶点34个,其中核心靶点包括转录因子AP-1(JUN)、肿瘤坏死因子(TNF)、丝/苏氨酸蛋白激酶1(AKT1)、钙黏蛋白相关蛋白(CT-NNB1)、血管内皮生长因子A(VEGFA)、有丝分裂原活化蛋白激酶8(MAPK8)、血管细胞粘附分子-1(VCAM1)、一氧化氮合成酶2(NOS2)、胞间粘附分子1(ICAM1)、E-选择素(SELE)。GO富集分析得到GO条目30条;KEGG通路富集筛选出通路前10条主要通路,包括流体切应力与动脉粥样硬化、糖尿病并发症中的晚期糖基化终末产物(AGEs)-糖基化终末产物受体(RAGE)信号通路、癌症的途径、肿瘤坏死因子信号通路、卡波济肉瘤相关疱疹病毒感染、非酒精性脂肪性肝病、白介素-17信号通路、C型凝集素受体信号通路、弓形体病、癌症中的蛋白聚糖等。推测与糖尿病肾病关系最为密切的为糖尿病并发症中的AGE-RAGE信号通路。分子对接结果显示,牛蒡子活性成分与多个靶点对接,其中β-谷甾醇与AKT1、山柰酚与TNF的结合能较低。结论:牛蒡子可能通过多成分、多靶点、多通路发挥抗炎、减少氧化应激等作用治疗糖尿病肾病。
Objective:To explore the potential active components and mechanism of Fructus Arctii on diabetic nephropathy.Methods:The active components,targets and two-dimensional structure diagram of Fructus Arctii were collected through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The related targets of diabetic nephropathy were obtained from TTD database,Drugbank database,GeneCards database and OMIM database,the repeated targets were eliminated,and then the Uniprot ID of each target was determined in combination with Uniprot database.On the basis of data from String database,the topological value of PPI network is calculated by the Network Analyzer and cytoHubba plugin of Cytoscape 3.7.0 software,and the topological network diagram for important targets is constructed.The network diagram of“active ingredient-target-pathway”is drawn.The core targets were imported into Metascape database for GO biological process enrichment analysis and KEGG analysis.The crystal structure of key target protein was downloaded from RSCB database,docked by AutoDock,and visualized by Pymol software.Results:Fructus Arctii has 8 active components and 80 main targets,and 34 targets were obtained after intersection with diabetic nephropathy targets.The core targets include transcription factor AP-1(JUN),tumor necrosis factor(TNF),serine-threonine kinase(AKT1),catenin protein beta 1(CT-NNB1),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase(MAPK8),vascular cell adhesion molecule-1(VCAM1),nitric oxide synthase 2(NOS2),intercellular adhesion molecule-1(ICAM1)and E-selectin(SELE).Thirty GO items were obtained by GO enrichment analysis,and the top 10 main pathways were selected by KEGG pathway enrichment including fluid shear stress and atherosclerosis,advanced glycosylation end products(AGEs)-receptor of AGEs(RAGE)signaling pathway in diabetic complications,cancer pathway,tumor necrosis factor signaling pathway,Kaposi’s sarcoma-associated herpes virus infection,non-alcoholic fatty liver disease,Interleukin-17 signaling pathway,C-type lectin receptor signaling pathway,toxoplasmosis,proteoglycan in cancer,etc.It is speculated that AGE-RAGE signaling pathway in diabetic complications is the most closely related to diabetic nephropathy.The results of molecular docking showed that the active components of Fructus Arctii docked with multiple targets,and the binding energy betweenβ-sitosterol and AKT1,kaempferol and TNF was low.Conclusion:Fructus Arctiimay treat diabetic nephropathy through multiple components,multiple targets and multiple pathways.
作者
陈侃俊
王丽莉
窦丹波
CHEN Kanjun;WANG Lili;DOU Danbo(Department of Traditional Chinese Medicine,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《上海中医药大学学报》
CAS
2022年第S01期196-203,共8页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(81704150)
关键词
网络药理学
分子对接
牛蒡子
糖尿病肾病
network pharmacology
molecular docking
Fructus Arctii
diabetic nephropathy
作者简介
陈侃俊,男,硕士,住院医师,主要从事内科疾病的中医治疗临床研究;通信作者:窦丹波,主任医师,硕士生导师,E-mail:doudanbo@126.com
