基于网络药理学和分子对接探究姜黄素治疗糖尿病视网膜病变的药效机制  

Mechanism of curcumin in the treatment of diabetic retinopathy based on network pharmacology and molecular docking

作　　者：杜媛媛 王熠昀 赵蓉[2] 张积[1] 季晓燕[1] 陆佳羽 嵇芳芳 娄慧[1] 江自远 黄江[1,3] Du Yuanyuan;Wang Yiyun;Zhao Rong;Zhang Ji;Ji Xiaoyan;Lu Jiayu;Ji Fangfang;Lou Hui;Jiang Ziyuan;Huang Jiang(Department of Ophthalmology,The Second Affiliated Hospital of Soochow University,Suzhou 215004,China;Suzhou Medical College of Soochow University,Suzhou 215123,China;State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou 215123,China)

机构地区：[1]苏州大学附属第二医院眼科,苏州215004 [2]苏州大学苏州医学院,苏州215123 [3]苏州大学放射医学与辐射防护国家重点实验室,苏州215123

出　　处：《中华实验眼科杂志》2023年第12期1152-1159,共8页Chinese Journal Of Experimental Ophthalmology

基　　金：江苏省中医药科技发展计划项目(YB2020060);放射医学与辐射防护国家重点实验室项目(GZK1202141);苏州市科技发展计划(医疗卫生科技创新)项目(SKY2022157);苏州大学附属第二医院博士、留学归国人员预研项目(SDFEYBS1903)。

摘　　要：目的应用网络药理学及分子对接的相关理论方法探究姜黄素治疗糖尿病视网膜病变(DR)的作用机制。方法利用SEA及SwissTargetPrediction数据库在线预测化合物作用的靶点;通过CTD数据库提供与疾病相关的各种靶点;运用Venny数据库映射匹配不同基因,并取二者交集;采用GeneMANIA数据库构造出交集基因的蛋白互作网络图,采用Cystoscape软件进行更精确的分析和可视化,借助WebGestalt数据库进行富集分析,最后利用AutoDock Vina对核心靶点进行分子对接。结果得到姜黄素作用靶点52个,DR对应的靶点1599个,共同作用的靶点48个。核心靶点为丝氨酸/苏氨酸-蛋白激酶1(AKT1)、肿瘤坏死因子α(TNF-α)、表皮生长因子受体(EGFR)、信号转导及转录激活因子3(STAT3)以及热休克蛋白90α家族A类成员1(HSP90AA1)。富集分析结果显示,这些靶点主要与EGFR酪氨酸激酶抑制剂耐药性信号通路、缺氧诱导因子1(HIF-1)信号通路、白细胞介素-17(IL-17)信号通路以及晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路等有关。结论姜黄素可能通过调控多条信号通路来抑制炎症反应和对抗氧化应激等过程,从而发挥治疗DR的作用。Objective To investigate the mechanism of curcumin in the treatment of diabetic retinopathy(DR)by network pharmacology and molecular docking.Methods The compounds targets of curcumin were predicted by SEA and SwissTargetPrediction databases,and the DR target genes were obtained by CTD database.The different genes were mapped and matched by Venny database to screen their intersections.The intersecting genes were submitted to GeneMANIA database to construct a protein-protein interaction network.WebGestalt database was used to conduct enrichment analysis and AutoDock Vina was used to perform molecular docking of the core targets.Results A total of 52 targets of curcumin,1599 targets of DR and 48 intersecting targets were detected.The core targets were serine/threonine-protein kinase 1(AKT1),tumor necrosis factor-α(TNF-α),epidermal growth factor receptor(EGFR),signal transduction and activator of transcription 3(STAT3)and heat shock protein 90 alpha family class A member 1(HSP90AA1).Enrichment analysis suggested that these targets were mainly associated with signaling pathways,including the EGFR tyrosine kinase inhibitor resistance signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,interleukin(IL)-17 signaling pathway and advanced glycosylation end product-the receptor of advanced glycosylation end product(AGE-RAGE)signaling pathway.Conclusions Curcumin may play an important role in the treatment of DR by regulating multiple signaling pathways to inhibit the inflammatory response and combat oxidative stress.

关 键 词：姜黄素 糖尿病视网膜病变 网络药理学 基因 

分 类 号：R285[医药卫生—中药学]