摘要
目的基于网络药理学方法和分子对接技术探讨肝豆灵治疗肝豆状核变性认知障碍的作用机制。方法通过TCMSP数据库检索肝豆灵六味中药的有效化学成分及潜在靶点,并将所获靶点导入到Uniprot数据库进行标准基因名转化;通过GeneCards、OMIM、PharmGkb、TTD数据库查询肝豆状核变性认知障碍的相关靶点;利用R 4.0.3软件获得肝豆灵与肝豆状核变性认知障碍的交集靶点;借助String数据库和Cytoscape 3.8. 0软件构建PPI网络,筛选核心靶点;应用DAVID数据库进行GO生物功能和KEGG通路富集分析;运用AutoDockTools 1.5. 6及Autodock vina 1.1. 2软件进行分子对接。结果共收集得到肝豆灵的基因靶点218个,肝豆状核变性认知障碍相关靶点4 858个,交集靶点189个,其交集靶点主要富集于2 922个生物功能及175条信号通路上。分子对接结果显示度值排名前3的核心靶点与其对应的化学成分之间均有较强的相互作用,其中JUN与槲皮素的结合性最好。结论肝豆灵治疗肝豆状核变性认知障碍具有多成分、多靶点、多通路的特点,可通过JUN、STAT3、TP53等核心靶点调控PI3K-AKT、AGE-RAGE等信号通路来降低活性氧簇水平,减轻神经炎症反应,抑制神经细胞凋亡,发挥其保护神经细胞、改善认知的效用。
Aim To explore the mechanism of GanDouLing in the treatment of cognitive impairment in Wilson Disease based on network pharmacology and molecular docking technology.Methods TCMSP database was used to search the effective chemical components and potential targets of GanDouLing, and the target was imported into UniProt database for standard gene name transformation. Genecards, OMIM, PharmGKB and TTD databases were used to search the related targets of cognitive impairment in Wilson Disease. R 4.0.3 software was used to obtain the intersection targets of GanDouLing and cognitive impairment of Wilson Disease. With the help of string database and Cytoscape 3.8.0 software, PPI network was constructed to screen core targets. The biological function of GO and the enrichment of KEGG pathway were analyzed by David database. AutodockTools 1.5.6 and Autodock Vina 1.1.2 were used for molecular docking.Results A total of 218 gene targets of GanDouLing, 4 858 targets related to cognitive impairment of Wilson Disease and 189 intersecting targets were collected. The intersecting targets were mainly enriched in 2 922 biological functions and 175 signaling pathways. Molecular docking results showed that there were strong interactions between the top three core targets and their corresponding chemical components, and JUN had the best binding ability with quercetin.Conclusions GanDouLing has the characteristics of multi-component, multi-target and multi-channel in the treatment of cognitive impairment of Wilson Disease. It can regulate PI3 K-Akt, AGE-RAGE and other signal pathways through JUN, STAT3, TP53 and other core targets to reduce the level of reactive oxygen species, reduce the neuroinflammatory response, inhibit the apoptosis of nerve cells, and play a role in protecting nerve cells and improving cognition.
作者
赵晨玲
董婷
杨文明
江张胜
田丽伟
ZHAO Chen-ling;DONG Ting;YANG Wen-ming;JIANG Zhang-sheng;TIAN Li-wei(Graduate School,Anhui University of Chinese Medicine,Hefei 230038,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2022年第1期133-139,共7页
Chinese Pharmacological Bulletin
基金
安徽省自然科学基金资助项目(No 1808085MH263)
安徽中医药大学第一附属医院临床科学研究项目(No 2020yfyzc01)。
关键词
肝豆灵
肝豆状核变性
认知障碍
网络药理学
分子对接
作用机制
GanDouLing
Wilson disease
cognitive impairment
network pharmacology
molecular docking
mechanism
作者简介
赵晨玲(1996-),女,硕士生,研究方向:中医脑病药理与临床,E-mail:1119489148@qq.com;通信作者:董婷(1979-),女,博士,副教授,博士生导师,研究方向:中医脑病药理与临床,E-mail:876786557@qq.com。
