摘要
目的基于网络药理学方法探究山药治疗阿尔茨海默病的潜在作用机制。方法通过TCMSP数据库进行山药潜在化学成分获取和靶点预测,运用GeneCards及OMIM数据库预测筛选与阿尔茨海默病相关的基因,采用R软件进行药物靶点与疾病靶点映射匹配。通过Cytoscape软件进行疾病-药物-成分-靶点可视化网络建立,借助String数据库在线平台进行蛋白互作网络构建,采用DAVID数据库进行生物过程及通路注释,采用R软件进行通路图绘制。通过Autodock vina分子对接软件对网络药理学结果进行验证。结果通过筛选共得到山药主要化合物16种,药物靶点144个,与AD相关的靶点24个,主要影响G蛋白偶联氨受体活性、甾类激素、核受体的活性、转录因子的活性,直接配体调控序列特异性DNA结合等生物过程,涉及神经活性配体受体交互通路、钙信号通路、卡波西肉瘤相关疱疹病毒感染通路、乳腺癌通路等。Autodock vina分子对接结果表明,山药活性成分与重要靶点结合活性较好,结果可靠性较高。结论山药具有多成分、多靶点、多过程的作用特征,其主要通过影响胆碱能神经系统及PI3K-Akt-mTOR信号通路,降低Aβ蛋白的沉积来治疗阿尔茨海默病,另外NF-κB通路、Wnt-GSK3β通路等与消化系统相关,可能是山药健脾补气角度治疗阿尔茨海默病的重要依据。
Objective To explore the potential mechanism of Rhizoma Dioscoreae in the treatment of Alzheimer′s disease based on network pharmacology.Methods The potential chemical composition and target prediction of Rhizoma Dioscoreae were obtained through the TCMSP database.GeneCards and OMIM databases were used to predict and screen genes related to Alzheimer′s disease.The R software was used to map drug targets to disease targets.The disease-drug-component-target visualization network was set up with Cytoscape software,the protein database interaction network was built with the String database online platform,the DAVID database was used for annotation of biologi-cal processes and pathways,and the R software was used for draw pathway.The network pharmacology analysis results were verified by Autodock vina software.Results A total of 16 main compounds of Rhizoma Dioscoreae,144 drug targets,and 24 AD-related targets were obtained through screening,which mainly affected the activity of G protein-coupled ammonia receptors,steroid hormones,nuclear receptors,and transcription factors.Biological processes such as activity,direct ligand regulation sequence-specific DNA binding,involve neuroactive ligand receptor interaction pathways,calcium signaling pathways,Kaposi′s sarcoma-associated herpes virus infection pathways,and breast cancer pathways.The docking results of Autodock vina showed that active ingredients of Rhizoma Dioscoreae had good binding activity with important targets.Conclusion The results of the study confirm that Rhizoma Dioscoreae has multi-component,multi-target,multi-process action characteristics.It is preliminarily explained that it mainly treats Alzheimer by affecting the cholinergic nervous system and PI3K-Akt-mTOR signaling pathway and reducing the deposition of Aβprotein.Meanwhile,the NF-κB pathway and Wnt-GSK3βpathway are related to the digestive system,which may be an important basis for nourishing spleen qi treatment of Alzheimer′s disease with Rhizoma Dioscoreae.
作者
李虹竹
许能贵
易玮
赵家莹
LI Hong-zhu;XU Neng-gui;YI Wei;ZHAO Jia-ying(The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,China;Medical College of Acupuncture and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Clinical Research Center,South China Research Center for Acupuncture and Moxibustion,Medical College of Acu-Moxi and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510006,China)
出处
《实用药物与临床》
CAS
2022年第2期119-127,共9页
Practical Pharmacy and Clinical Remedies
基金
国家自然基金青年基金项目(81704168)。
关键词
阿尔茨海默病
山药
网络药理学
分子对接
Alzheimer′s disease
Rhizoma Dioscoreae
Network pharmacology
Molecular docking
作者简介
通信作者:赵家莹。
