黄芪活性成分抗衰老作用机制的网络药理学研究
投稿时间:2020-06-11     点此下载全文
引用本文:张婷,王宏雅,魏桂杰,赵雯雯,孙秀蕊,张哲,马鹏凯,张玉杰.黄芪活性成分抗衰老作用机制的网络药理学研究[J].中国现代中药,2021,23(5):807-814
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作者中文名作者英文名单位中文名单位英文名E-Mail
张婷 ZHANG Ting 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
王宏雅 WANG Hong-ya 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
魏桂杰 WEI Gui-jie 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
赵雯雯 ZHAO Wen-wen 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
孙秀蕊 SUN Xiu-rui 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
张哲 ZHANG Zhe 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China  
马鹏凯 MA Peng-kai 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China 马鹏凯,讲师,博士,研究方向:中药质量控制;E-mail:mapengkai1990@126.com 
张玉杰 ZHANG Yu-jie 北京中医药大学 中药学院,北京102488 School of Chinese Materia Medica, Bejing University of Chinese Medicine,Beijing 102488, China 张玉杰,教授,博士生导师,研究方向:中药质量控制;E-mail:zhyj227@126.com 
中文摘要:目的:运用网络药理学方法探讨黄芪抗衰老的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获得黄芪化学成分,以生物利用度(OB)、类药性(DL)为条件筛选主要活性成分;利用TCMSP和PharmMapper数据库预测黄芪活性成分靶点;在OMIM数据库和GeneCards数据库中输入关键词“aging”,搜索与衰老相关的疾病靶点;借助Cytoscape 3.2.1软件构建“药物-疾病-靶点”的可视化网络;通过STRING网站构建蛋白质-蛋白质相互作用(PPI)网络,并筛选核心靶点;通过CB-Dock网站对成分与靶点进行分子对接验证;应用DAVID数据库对靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路分析。结果:筛选得到黄芪24个活性成分,对应385个作用靶点;筛选出衰老相关靶点23 997个,取交集得到黄芪与衰老相关靶点377个,其中核心靶点为蛋白激酶B1(Akt1)、丝裂原活化蛋白激酶1(MAPK1)、Jun、白细胞介素-6(IL-6)、MAPK8、表皮生长因子受体(EGFR)、血管内皮生长因子A(VEGFA)、表皮生长因子(EGF)、骨髓细胞瘤病毒癌基因同源物(MYC)和白细胞介素-8(CXCL8);分子对接结果显示,黄芪活性成分与靶蛋白Akt1和MAPK1的结合能力较好;GO功能显著富集在氧化应激反应、活性氧代谢等生物过程;KEGG富集信号通路161条。结论:黄芪中黄酮和皂苷类化合物可能是其抗衰老的物质基础;黄芪可通过Akt1等靶点调节糖基化终末产物及其受体(AGE-RAGE)、缺氧诱导因子-1(HIF-1)等信号通路发挥其抗衰老作用,为其深入研究提供参考。
中文关键词:黄芪  抗衰老  网络药理学  药物靶点  衰老靶点  分子对接
 
Study on Anti-aging Mechanism of Active Components of Astragali Radix Based on Network Pharmacology
Abstract:Objective:To explore the mechanism of Astragali Radix for anti-aging by means of network pharmacology. Methods:Chemical compositions of Astragali Radix were obtained by Traditional Chinese Medicine Systems Pharmacology(TCMSP), the main active ingredients were screened under the conditions of oral bioavailability (OB) and drug-likeness (DL);TCMSP and PharmMapper database were used to predict the active component targets. The key word “aging” was input into OMIM database and GeneCards database to search for disease targets;Cytoscape 3.2.1 software was used to construct a visual network diagram of ″drug-disease-target″;PPI protein interaction network was constructed through STRING website, and core targets were screened;molecular docking between the components and the target was verified through the CB-Dock website;David database was used for the enrichment analysis of gene ontology(GO) function and Kyoto encyclopedia of genes and genomes(KEGG) pathway. Results:The results showed that 24 active components and 385 targets of Astragali Radix were involved;23 997 aging-related targets were screened and 377 of them were obtained from the intersection of Astragali Radix and aging-related targets;The core target proteins were protein kinase B(Akt1),mitogen-activated protein kinase 1 (MAPK1), Jun, interleukin-6(IL-6), MAPK8, epidermal growth factor receptor(EGFR), vascular endothelial growth factor A(VEGFA), epidermal growth factor(EGF),myelocytomatosis viral oncogene homolog(MYC) and interleukin-8(CXCL8);Molecular docking showed that the binding ability of the active components to the target protein Akt1 and MAPK1 was well;GO function is significantly enriched in biological processes such as oxidative stress reaction and active oxygen metabolism. KEGG enriched 161 signaling pathways. Conclusion:The active ingredients of flavonoids and saponins in Astragali Radix are the material basis for the treatment of aging;Astragali Radix can regulate AGE-RAGE signaling pathway, HIF-1 signaling pathway through Akt1 and other targets to exert its anti-aging effect, which provides a theoretical reference for further research.
keywords:Astragali Radix  anti-aging  network pharmacology  drug targets  aging targets  molecular docking
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