摘要
目的采用网络药理学的方法,预测当归治疗阿尔茨海默病(AD)的潜在作用靶点及其作用机制。方法通过中药系统药理学(TCMSP)数据库筛选当归的主要活性成分,并在Swiss Target Prediction平台对当归活性成分的作用靶点进行预测。通过Genecards数据库筛选AD的主要靶点,将当归有效成分靶点与AD的主要靶点取交集,得到当归治疗AD的靶点。利用String平台构建蛋白质相互作用(PPI)网络,运用Metascape平台进行基因本体(GO)及代谢途径分析数据库(KEGG)进行富集分析。应用Autodock vina软件对网络药理学结果进行验证。结果经筛选获得西多糖苷、豆甾醇、α-胡麻烯、β-谷甾醇等10种当归治疗AD的有效成分,329个潜在药物靶点,当归有效成分与AD共有靶点75个,Sitogluside,beta-sitosterol,Stigmasterol可能是当归治疗AD的关键活性成分。PPI网络分析显示,AKT1、PTGS2、MAPK14可能是当归治疗AD的核心靶点。通路分析提示当归治疗AD的机制可能与cGMP-PKG信号通路、NF-kB信号通路、神经活性配体-受体相互作用等有关。分子对接结果表明,当归主要活性成分Sitogluside,beta-sitosterol,Stigmasterol与关键靶点AKT1、PTGS2、MAPK14结合活性较好。结论当归具有多成分、多靶点和多通路的发挥治疗AD的作用。
Objective The network pharmacology method was used to predict the potential targets and mechanisms of Angelica sinensis in the treatment of Alzheimer’s disease(AD).Methods The main active components of Angelica sinensis were screened through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,and the target of the active components of Angelica sinensis was predicted on the Swiss Target Prediction platform.The main targets of AD were screened through the Genecards database,and the targets of the active ingredients of Angelica sinensis were intersected with the main targets of AD to obtain the targets of Angelica sinensis for the treatment of AD.The protein interaction(PPI)network was constructed using the String platform,and the Gene Ontology(GO)and metabolic pathway analysis database(KEGG)were used for enrichment analysis using the Metascape platform.The results of network pharmacology were verified by Autodock vina software.Results After screening,10 active ingredients of Angelica sinensis(such as Sitogluside,Stigmasterol,α-copaene,and beta-sitosterol),329 potential drug targets,and 75 targets in common between the active ingredients of Angelica sinensis and AD were obtained in the treatment of AD.Sitogluside,beta-sitosterol,Stigmasterol may be the key active ingredients of Angelica sinensis in the treatment of AD.PPI network analysis showed that AKT1,PTGS2 and MAPK14 may be the core targets of Angelica sinensis in the treatment of AD.Pathway analysis suggested that the mechanism of Angelica sinensis in treating AD may be related to cGMP-PKG signaling pathway,NF-kB signaling pathway,neuroactive ligand-receptor interaction and so on.Molecular docking results showed that the main active components of Angelica sinensis,including Sitogluside,beta-sitosterol and Stigmasterol,had better binding activity to key targets AKT1,PTGS2 and MAPK14.Conclusion Angelica sinensis has multi-component,multi-target and multi-pathway features to play a role in the treatment of AD.
作者
叶长青
罗洪斌
詹杰
杨娇
周戈
YE Changqing;LUO Hongbin;ZHAN Jie;YANG Jiao;ZHOU Ge(Medical School,Hubei Minzu University,Enshi 445000,China;Institute of Neurological and Psychiatric Comorbidity,Hubei Minzu University,Enshi 445000,China)
出处
《湖北民族大学学报（医学版）》
2022年第4期7-13,共7页
Journal of Hubei Minzu University(Medical Edition)
基金
国家自然科学基金项目(81260172,81660223)。
关键词
当归
网络药理学
阿尔茨海默病
分子对接
靶点预测
Angelica sinensis
Network pharmacology
Alzheimer’s disease
molecular docking
target prediction
