摘要
目的:利用网络药理学方法从系统网络水平上研究当归芍药散(DSS)治疗阿尔兹海默病(AD)的作用机制。方法:从中药系统药理学数据库(TCSMP)中筛选DSS治疗AD的活性成分,并构建药物-靶标-疾病网络,运用生物信息学分析方法进行靶器官定位网络、GO分析和Pathway富集分析。结果:通过网络药理学方法筛选出DSS活性成分51种,显示其活性化合物的预测靶点377个,197个靶点与AD相关,DSS活性化合物的药效作用靶点高度富集到与AD相关的信号通路,与减少Aβ的聚集和抑制tau过度磷酸化以及抗炎和抗凋亡等生物学过程密切相关,其靶向基因的mRNA表达主要富集在肝、心脏、和脑。结论:DSS活性化合物以协同的方式与多个靶点多种途径相互作用,主要以抗炎、抗凋亡、增强代谢和增强免疫系统等途径对AD产生重要的治疗作用。
Objective： To study the mechanism of action of Danggui Shaoyao San （DSS） in the treatment of Alzheimer＇s disease （AD） from a systematic network level using network pharmacology. Methods： The active ingredients of DSS in treating AD was screened from the Traditional Chinese Medicine System Pharmacology Database （TCSMP）, and the drugs-targets-disease network was built. Target organ localization network, GO analysis and Pathway enrichment analysis were used for bioinformatics analysis. Results： 51 kinds of DSS active ingredients were screened by network pharmacology, showing 377 predicted targets of active compounds. Among them, 197 targets were associated with AD, and the pharmacodynamic targets of DSS active compounds were highly enriched with AD-related signals. The pathway was closely related to the reduction of A- aggregation and inhibition of tau hyperphosphorylation and biological processes such as anti-inflammatory and anti-apoptosis, and the mRNA expression of the targeted gene was mainly enriched in the liver, heart, and brain. Conclusion： DSS active compounds interact with multiple targets in multiple ways in a synergistic manner, mainly to produce important therapeutic effects on AD with anti-inflammatory, anti-apoptotic, enhancing metabolism and immune system.
作者
宋祯彦
陈易璇
余婧萍
成绍武
Song Zhenyan;Chen Yixuan;Yu Jingping;Cheng Shaowu(The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2018年第6期834-846,共13页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委面上基金项目(81774129):基于"痰浊瘀血"理论从蛋白质异戊二烯化修饰探讨当归芍药散改善AD认知功能的机制
负责人:成绍武
湖南省中医药管理局科研项目(2018025):基于Ras-ERK信号通路调控AMPA受体转运探讨当归芍药散改善AD认知功能的机制
负责人:宋祯彦
湖南省自然科学基金面上项目(2018JJ2296):基于mTOR通路与蛋白异戊二烯化修饰的关系探讨当归芍药散改善突触损伤的机制研究
负责人:成绍武
关键词
网络药理学
当归芍药散阿尔兹海默病
系统分析
Network pharmacology
Danggui Shaoyao San
Alzheimer＇ s disease
system analysis
