基于网络药理学和分子对接研究黄芩治疗白癜风的作用机制

Exploring the mechanism of Scutellariae Radix in treatment of vitiligo based on network pharmacology and molecular docking

目的利用网络药理学方法研究黄芩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)筛选得到黄芩中的活性成分及其作用靶点,通过SwissTargetPrediction数据库检索补充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;将黄芩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;利用Cytoscape 3.9.1软件,构建"黄芩-活性成分-白癜风靶点"网络并筛选核心靶点;使用Metascape数据库对潜在作用靶点进行基因本体论(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。结果共筛选得到黄芩素、汉黄芩素、刺槐素、木蝴蝶素a、表小檗碱、去甲汉黄芩素、5,7,4'-三羟基-8-甲氧基黄酮等36个活性成分,作用于3868个潜在靶点,白癜风相关靶点1349个,黄芩-白癜风的交集靶点113个;PPI网络分析得到肿瘤蛋白P53(TP53)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、信号转导和转录激活因子3(STAT3)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶1(MAPK1)、白细胞介素-6(IL-6)、胱天蛋白酶3(CASP3)、雌激素受体(ESR1)共8个核心作用靶点;GO和KEGG富集分析显示,黄芩治疗白癜风主要涉及胰腺癌、内分泌抵抗、神经营养素信号通路、细胞凋亡、乙型肝炎、细胞衰老等信号通路。分子对接结果显示黄芩素、汉黄芩素、刺槐素、木蝴蝶素a、表小檗碱、去甲汉黄芩素、5,7,4'-三羟基-8-甲氧基黄酮7个核心成分与核心靶点具有较好的结合能。结论黄芩可能通过调控内分泌、神经、细胞衰老和凋亡以及炎症等方面发挥治疗白癜风的作用,为后续研究黄芩治疗白癜风提供参考。

Objective To study the target and mechanism of Scutellariae Radix in treatment of vitiligo by means of network pharmacology.Methods The active components and their action targets of Scutellariae Radix were screened by using the traditional Chinese Medicine system Pharmacology Database and Analysis platform(TCMSP),and the action targets of each active component were searched and supplemented by SwissTargetPrediction database.The related targets of vitiligo were obtained through OMIM and GeneCards databases,and the action targets of active components were intersected.The intersection of active components of Scutellaria baicalensis and vitiligo was introduced into String database to construct protein interaction(PPI)network.Using Cytoscape 3.9.1 software,the network of"Scutellariae Radix active ingredient-vitiligo target"was constructed and the core targets were screened.GO functional enrichment analysis and KEGG pathway enrichment analysis of potential targets were carried out by using Metascape database.AutoDockTools1.5.7 software was used for molecular docking verification and PyMol software was used to visualize the results.Results A total of 36 active components,including baicalein,wogonin,sophorin,sophorin a,epiberberine,demethylwogonin,5 maestrin,trihydroxy-8-methoxy flavonoid,were screened,which acted on 3868 potential targets,1349 targets related to vitiligo and 113targets for the intersection of Scutellaria baicalensis-vitiligo.PPI network analysis showed 8 core targets:TP53,AKT1,STAT3,TNF,MAPK1,IL-6,CASP3,ESR1.GO and KEGG enrichment analysis showed that Scutellariae Radix in the treatment of vitiligo mainly involved pancreatic cancer,endocrine resistance,neurotrophin signal pathway,apoptosis,hepatitis B,cell senescence and other signal pathways.The results of molecular docking showed that the seven core components of baicalein,wogonin,sophorin,sophorin a,epiberberine,demethylated wogonin and 5-methoxy-4-hydroxy-8-methoxy flavonoids had good binding energy with core targets.Conclusion Scutellariae Radix may play a role in treatment of vitiligo by regulating endocrine,nerve,cell senescence,apoptosis and inflammation,which provides a reference for the follow-up study of Scutellariae Radix in the treatment of vitiligo.