摘要
目的:基于网络药理学方法探讨七福饮治疗阿尔茨海默病(AD)的活性成分及其作用机制。方法:应用中药系统药理学(TCMSP)分析平台、ETCM数据库、SymMap数据库筛选七福饮的活性成分及作用靶点。利用Genecards数据库、OMIM数据库、Pubmed-Gene数据库筛选AD相关靶点,取交集得到七福饮治疗AD的靶点。将上述靶点导入STRING数据库,利用Cytoscape软件构建"活性成分-作用靶点"网络和蛋白相互作用(PPI)网络,筛选出关键成分和关键靶点,并进行GO生物功能注释和KEGG通路分析。应用Schrodinger软件进行分子对接验证。结果:对七福饮共筛选出106个活性成分、511个作用靶点,AD相关靶点369个。"活性成分-作用靶点"网络分析显示,山柰酚、β-谷甾醇、豆甾醇可能是七福饮治疗AD的关键活性成分。PPI网络分析显示,丝氨酸/苏氨酸激酶1(AKT1)、脑源性神经营养因子(BDNF)、胰岛素(INS)、丝裂原活化蛋白激酶3(MAPK3)、肿瘤蛋白p53(TP53)可能是七福饮治疗AD的关键靶点。通路分析提示,七福饮治疗AD的机制可能与多巴胺能突触、cAMP信号通路、白介素-17信号通路、磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-AKT)信号通路等有关。分子对接显示,AKT1与腺嘌呤、BDNF与Inermine、INS与川芎内酯E、MAPK3与异甘草黄酮醇、TP53与7-乙酰氧基-2-甲基异黄酮的结合能力较强。结论:七福饮通过多成分、多靶点、多通路减轻神经元损伤,发挥治疗AD的作用。
Objective: To explore the active ingredients and action mechanisms of Qifu Decoction in the treatment of Alzheimer’s disease(AD) based on network pharmacology. Methods: The active ingredients and action targets of Qifu Decoction were screened out by TCMSP analysis platform, ETCM database and SymMap database. Genecards database, OMIM database and Pubmed-Gene database were used to screen the targets related to AD, and the targets of Qifu Decoction in treating AD were obtained after the intersection. The above targets were imported into the STRING database, and the networks of "active ingredients-action targets" and protein-protein interaction(PPI) were constructed using the Cytoscape software. The key ingredients and targets were screened out, and GO biological function annotation and KEGG pathway analysis were carried out. The molecular docking based on Schrodinger software was used for verification. Results:For Qifu Decoction, a total of 106 compounds and 511 action targets, and 369 potential targets related to AD were screened out. The network analysis of "active ingredients-action targets" showed that kaempferol, β-sitosterol and stimasterol may be the key active ingredients of Qifu Decoction in the treatment of AD. The PPI network analysis showed that serine/threonine kinase 1(AKT1), brain-derived neurotrophic factor(BDNF), insulin(INS), mitogen-activated protein kinase 3(MAPK3) and tumor protein p53(TP53) may be the key targets of Qifu Decoction in the treatment of AD. Pathway analysis suggested that the mechanisms of Qifu Decoction in the treatment of AD might be related to dopaminergic synapse, cAMP signal pathway, interleukin-17 signal pathway, phosphatidylinositol-3-kinase-protein kinase B(PI3K-AKT) signal pathway and so on.Molecular docking found that AKT1 and adenine,BDNF and inermine,INS and senkyunolide-E,MAPK3 and isolicoflavonol,TP53 and 7-acetoxy-2-methylisoflavone showed strong binding.Conclusion:Qifu Decoction can alleviate neuronal damage through multi-components,multi-targets and multi-pathw
作者
李妍芃
王萍
LI Yanpeng;WANG Ping(Department of Pharmacy,Beijing Longfu Hospital,Beijing 100010,China;Beijing Institute of Integrated Traditional Chinese and Western Medicine for Elderly Health,Beijing 100010,China)
出处
《上海中医药大学学报》
CAS
2020年第5期77-84,共8页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(81773838)
北京市科协金桥工程种子资助项目(ZZ19060)。
关键词
七福饮
阿尔茨海默病
网络药理学
生物信息学
Qifu Decoction
Alzheimer’s disease
network pharmacology
bioinformatics
