基于网络药理学和分子对接研究甘草治疗白癜风的作用机制  

Mechanism of Glycyrrhizae Radix et Rhizoma in treatment of vitiligo based on network pharmacology and molecular docking

作　　者：刘浩 张辛芸 杨宇萍 范潇晓 王文琪 梁敬臣 刘永刚[1] LIU Hao;ZHANG Xin-yun;YANG Yu-ping;FAN Xiao-xiao;WANG Wen-qi;LIANG Jing-chen;LIU Yong-gang(Beijing University of Chinese Medicine,Beijing 100029,China;Beijing Sanheli Biotechnology Co.,Ltd.,Beijing 100068,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京三和丽生物科技有限公司,北京100068

出　　处：《现代药物与临床》2023年第10期2418-2426,共9页Drugs & Clinic

基　　金：国家重点研发计划项目(2018YFC1706500)。

摘　　要：目的利用网络药理学和分子对接方法研究甘草治疗白癜风的作用靶点和机制。方法使用中药系统药理学数据库与分析平台(TCMSP)筛选得到甘草中的活性成分,使用SwissTargetPrediction数据库预测各个活性成分的作用靶点;通过OMIM、GeneCards数据库获取白癜风的相关靶点,与活性成分作用靶点取交集;利用Cytoscape 3.9.1软件对交集靶点进行拓扑学分析并筛选得到甘草主要活性成分,构建得到“甘草主要活性成分–白癜风靶点”网络;将甘草活性成分和白癜风的交集靶点导入String数据库构建靶点间的蛋白相互作用(PPI)网络;使用Metascape数据库对潜在作用靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;使用AutoDockTools 1.5.7软件进行分子对接验证并使用PyMol软件对结果进行可视化处理。结果共筛选得到谷甾醇、格里西轮、光果甘草宁、甘草查尔酮B、刺芒柄花黄素等84个活性成分,作用于8400个潜在靶点,白癜风相关靶点1349个,甘草–白癜风的交集靶点133个;PPI网络分析得到蛋白激酶B1(Akt1)、信号传导和转录激活蛋白3(STAT3)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、有丝分裂原活化蛋白激酶1(MAPK1)、血管内皮生长因子A(VEGFA)6个核心作用靶点;GO和KEGG富集分析显示,甘草治疗白癜风主要涉及病毒感染、癌症、细胞凋亡、乙型肝炎、细胞衰老等信号通路。分子对接结果显示谷甾醇、格里西轮、光果甘草宁、(2S)-7-羟基-2-(4-羟基苯基)-8-(3-甲基丁烯-2-乙烯基)色曼-4-酮、甘草查耳酮B、刺芒柄花黄素6个核心成分与核心靶点具有较好的结合能。结论甘草可能通过调控细胞衰老和凋亡、免疫功能、炎症等多个方面发挥治疗白癜风的作用,为后续研究甘草治疗白癜风提供参考。Objective To study the target and mechanism of Glycyrrhizae Radix et Rhizoma in treatment of vitiligo based on network pharmacology and molecular docking.Methods Active components in Glycyrrhizae Radix et Rhizoma were screened by TCMSP,and the targets of each active component were predicted by SwissTargetPrediction database.The related targets of vitiligo were obtained through OMIM and GeneCards databases,and the targets of active components were intersected.Cytoscape 3.9.1 software was used to perform topological analysis on the intersection targets and screen out the main active components of Glycyrrhizae Radix et Rhizoma,and the network of Glycyrrhizae Radix et Rhizoma main active components-vitiligo target was constructed.Intersection targets of Glycyrrhizae Radix et Rhizoma active components and vitiligo were imported into the String database to construct PPI network between targets.Metascape database was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on potential targets.AutoDockTools 1.5.7 software was used for molecular docking verification and PyMol software was used to visualize the results.Results A total of 84 active ingredients such as sitosterol,glisiran,guangguo gancaoning,licochalcone B,formononetin and so on were screened,which acted on 8400 potential targets,1349 vitiligo related targets,and 133 Glycyrrhizae Radix et Rhizomvitiligo intersection targets.Six core targets of Akt1,STAT3,TNF,IL96,MAPK1,and VEGFA were obtained by PPI network analysis.GO and KEGG enrichment analysis showed that Glycyrrhizae Radix et Rhizom in treatment of vitiligo mainly involved signal pathways such as viral infection,cancer,apoptosis,hepatitis B,and cell senescence.The results of molecular docking showed that the seven core components of sitosterol,glycyrin,glabranin,(2S)-6-(2,4-dihydroxyphenyl)-2-(2-hydroxypropan-2-yl)-4-methoxy-2,3-dihydrofuro[3,2-g]chromen-7-one,licochalcone B,formononetin had good binding energy with the core targets.Conclusion Glycyrrhizae Radix et Rhizom ma

关 键 词：甘草 白癜风 网络药理学 分子对接 谷甾醇 格里西轮 光果甘草宁 甘草查尔酮B 刺芒柄花黄素 

分 类 号：R285[医药卫生—中药学]