摘要
目的:通过网络药理学和分子对接方法探讨黄芪-柴胡治疗甲亢的作用机制。方法:利用TCMSP数据库以生物利用度(oral bioavailability,OB)≥30%、类药指数(drug-likeness,DL)≥0.18筛选出黄芪-柴胡的活性成分及相对应的靶点,通过GeneCards、DisGeNET、TTD和Drugbank数据库以“Hyperthyroidism”为关键词检索相关靶点;获取中药与疾病交集靶点,并用Cytoscape软件中的“Degree”“Betweenness”“Closeness”选取关键靶点,在DAVID平台获取关键靶点的信息从而构建GO和KEGG通路富集分析;通过Autodock Tools 1.5.7软件将活性成分和与之有关的核心靶点进行分子对接。结果:筛选得到黄芪20个活性成分,224个靶点;柴胡17个活性成分,193个靶点;甲亢相关靶1358个;交集映射获得交集靶点76个。通过插件筛选出18个核心靶点进行GO功能富集分析得到306个条目,包括生物过程条目244个,细胞定位条目20个,分子功能条目42个。通过KEGG通路注释得96条信号通路,如HIF-1信号通路、IL-17信号通路、TNF信号通路等。分子对接结果显示,关键靶点AKT1、IL-6、TNF、IL-1β与对应活性成分都有较好亲和力。结论:中药黄芪-柴胡治疗甲亢通过多成分、多靶点、多通路协同起效,该研究为后续研究提供了充分的理论依据。
Objective:The mechanism of Astragalus-Bupleurum treatment for hyperthyroidism was investigated by network pharmacology and molecular docking methods.Methods:TCMSP database was used to screen out the active constituents of Astragalus bupleurum and their corresponding targets with bioavailability(OB)≥3o%and drug index(DL)≥0.18.Both GeneCards,DisGeNET,TTD and Drugbank databases were used to search the relevant targets with the key words Hyperthyroidism.To obtain the intersection targets between TCM and diseases,the key targets were selected using the"Degree","Betweenness"and"Closeness"in Cytoscape software,and the key target information was obtained on the DAVID platform to construct GO functional enrichment and KEGG pathway enrichment analysis.Autodock Tools 1.5.7 software was used to conduct molecular docking of core targets and their corresponding active components.Results:The results showed that 20 active ingredients(224 targets)of Astragalus and 17 active ingredients(193 targets)of Bupleurum were obtained.There were 1358 targets associated with hyperthyroidism.Intersection mapping obtained 76 intersection targets.Eighteen core targets were selected by the plug-in for GO functional enrichment analysis and 306 items were obtained,including 244 biological process items,20 cell localization items and 42 molecular function items.Ninety-six signaling pathways were annotated by KEGG pathway,such as HIF-1 signaling pathway,IL-17 signaling pathway,TNF signaling pathway,etc.Molecular docking results showed that the key targets of AKT1,IL-6,TNF and IL-1βhad good affinity with the corresponding active ingredients.Conclusion:Radix Astragalus Bupleurum is effective in treating hyperthyroidism through multi-component,multi-target and multi-pathway synergies.This study provides sufficient theoretical basis for subsequent research.
作者
陈帆
任君旭
张静
CHEN Fan;REN Jun-xu;ZHANG Jing(School of Basic Medicine,Hebei North University,Zhangjiakou,075000,China)
出处
《神经药理学报》
2023年第5期6-13,共8页
Acta Neuropharmacologica
