摘要
目的基于网络药理学方法预测倍半萜香豆素治疗阿尔茨海默症(Alzheimer′s disease,AD)的作用靶点和通路。方法采用文献检索和数据库分析的方法,构建AD治疗相关靶点蛋白库和具有显著抗AD作用的天然倍半萜香豆素小分子物质库。运用Maestro软件进行分子对接,垂钓与倍半萜香豆素结构结合密切的炎症靶点蛋白;采用Cytoscape 3.6.0软件构建"结构-靶点"和"靶点-靶点"关联网络;将得到的炎症靶蛋白导入DAVID 6.7在线数据库中,进行GO分析和KEGG通路分析。结果天然倍半萜香豆素抑制神经炎症的潜在核心靶点蛋白为K-RAS和TLR4,与MAPKs和TOLL样受体两条信号通路密切相关。结论本研究综合利用虚拟筛选技术和网络药理学方法预测分析了倍半萜香豆素类天然产物抑制神经炎症的作用靶点和信号通路,为深入研究倍半萜香豆素抗AD的作用机制提供了科学依据。
Objective To predict the target and pathway of sesquiterpene coumarins in the treatment of Alzheimer′s disease based on network pharmacology methods.Methods The target proteins library of AD therapy-related and natural sesquiterpene coumarins small molecule library with significant anti-AD effect were constructed by using the methods of literature retrieval and database analysis.Molecular docking was carried out using Maestro software,fishing for inflammatory target proteins that are closely bound to sesquiterpene coumarins.The correlation networks of"compound-target"and"target-target"were constructed by Cytoscape 3.6.0 software.The obtained inflammatory target protein was submitted to DAVID 6.7 online database for GO analysis and KEGG pathway analysis.Results K-RAS and TLR4 were potential target proteins of natural sesquiterpene coumarins inhibiting neuroinflammation,which were closely related TOLL-like receptor and MAPKs signaling pathways.Conclusion In this study,virtual screening technology and network pharmacological methods are comprehensively used to predict and analyze the target proteins and signal pathways of the natural products of sesquiterpene coumarins in inhibiting neuroinflammation,providing scientific basis for further research on the mechanism of sesquiterpene coumarins against AD.
作者
郭婷婷
周地
党文
顾希
王健
李宁
GUO Tingting;ZHOU Di;DANG Wen;GU Xi;WANG Jian;LI Ning(School of Traditional Chinese Medicine,Shenyang Pharmaceutical University,Shenyang 110016,China)
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2020年第1期69-76,共8页
Journal of Shenyang Pharmaceutical University
基金
国家自然科学基金资助项目(81673323).
关键词
虚拟筛选
网络药理学
倍半萜香豆素
神经炎症
阿尔茨海默症
virtual screening
network pharmacological
sesquiterpene coumarins
neuroinflammation
Alzheimer′s disease
作者简介
郭婷婷(1994-),女(汉族),山西临汾人,博士研究生,E-mail:18835170711@163.com;通信作者:李宁(1979-),女(汉族),河北保定人,教授,博士,主要从事中药、天然药物药效物质基础和质量控制的研究,Tel.024-43520739,E-mail:liningsypharm@163.com。
