摘要
目的 运用网络药理学和分子对接,研究黄芪桂枝五物汤治疗大动脉炎(TA)的作用机制。方法 用TCMSP数据库搜寻黄芪桂枝五物汤活性成分及作用靶点,使用GeneCards查找TA疾病靶点,利用CytoScape软件构建“药物-成分-靶点”可视化网络;交集得到黄芪桂枝五物汤治疗TA的预测靶点,运用STRING数据库将交集靶点行蛋白质-蛋白质相互作用(PPI)分析;利用DAVID数据库对预测靶点行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析;最后使用PyMOL和AutoDockTools进行关键成分与靶点的分子对接验证。结果 筛选得到黄芪桂枝五物汤主要成分包括槲皮素、山奈酚、β-谷甾醇、毛蕊异黄酮等;得到726个TA疾病靶点;PPI网络筛选出白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、白蛋白(ALB)、血管内皮生长因子A(VEGFA)等核心靶点;GO和KEGG富集分析结果表示黄芪桂枝五物汤治疗TA主要涉及白介素-17(IL-17)信号通路、肿瘤坏死因子信号通路等,可能通过对脂多糖的反应、炎症反应、细胞凋亡过程的负调节等发挥治疗作用。分子对接验证关键活性成分和核心靶点中结合能≤-5 kJ/mol占比93.8%,证明两者能够稳定对接。结论 黄芪桂枝五物汤中槲皮素、山奈酚、β-谷甾醇、毛蕊异黄酮等活性成分可通过抑制炎症、降低氧化应激等作用发挥对TA的治疗作用。
Objective To explore the mechanism of Huangqi Guizhi Wuwu Decoction in treating Takayasu arteritis based on network pharmacology and macromolecular docking.Methods Active ingredients and targets of Huangqi Guizhi Wuwu Decoction were searched in TCMSP database,disease targets of Takayasu arteritis(TA)were searched in GeneCards,and a"drug-ingredient-target"visualization network was constructed using Cytoscape software.The predicted targets for treating TA with Huangqi Guizhi Wuwu Decoction were obtained by intersection,and protein-protein interaction(PPI)analysis was performed on the intersection targets using STRING database.Gene ontology(GO)function enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the prediction targets using DAVID database.Finally,PyMOL and AutoDockTools were used to verify the macromolecular docking between critical ingredients and targets.Results The main ingredients of Huangqi Guizhi Wuwu Decoction screened include quercetin,kaempferol,β-sitosterol,calycosin,etc.A total of 726 TA disease targets were obtained.PPI network screened core targets such as interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB)and vascular endothelial growth factor A(VEGFA).The results of GO and KEGG enrichment analysis indicate that the treatment of TA by Huangqi Guizhi Wuwu Decoction mainly involves interleukin-17(IL-17)signaling pathway,tumor necrosis factor signaling pathway,etc.,which may play a therapeutic role through the response to lipopolysaccharide,inflammatory response,negative regulation of cell apoptosis and other functions.Macromolecular docking verified that the binding energy of critical active ingredients and core targets was≤-5 kJ/mol,accounting for 93.8%,which proved that they could dock stably.Conclusion Quercetin,kaempferol,β-sitosterol,calycosin,and other active ingredients in Huangqi Guizhi Wuwu Decoction can exert therapeutic effects on TA by inhibiting inflammation and reducing oxidative stress.
作者
汪佳丽
徐少华
付琦
刘涛
WANG Jiai;XU Shaohua;FU Qi;LIU Tao(Cardiothoracic&Vascular Surgery,Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine,Guangxi,Nanning 530201,China)
出处
《中国医药科学》
2023年第21期25-29,共5页
China Medicine And Pharmacy
基金
广西国际壮医医院院级学科外科学(心胸外科方向)(06)
广西中医药适宜技术开发与推广项目(GZSY21-43)
广西壮族自治区中医药管理局自筹经费科研课题项目(GXZYA20220159)
广西中医药大学校级科研项目(2019QN031,2019QN032)。
