基于网络药理学探讨覆盆子防治阿尔茨海默病的物质基础与作用机制

Discussion of the Material Basis and Mechanism of Raspberry in Treatment of AD by Basing on the Network Pharmacology

目的:运用网络药理学方法探讨覆盆子防治阿尔茨海默病(AD)的主要物质基础与作用机制。方法:收集Drugbank数据库和相关文献中的AD关键治疗靶点,利用TCMSP数据收集构建覆盆子的化学成分库;运用Discovery Studio软件进行分子虚拟对接,筛选出覆盆子中与AD关键靶点结合的化学成分集,再利用KEGG数据库对这些关键靶点进行通路富集分析,建立成分-靶点-通路关系,通过Cytoscape软件构建覆盆子成分-靶点-通路网络图。结果:从覆盆子中筛选出成分50个,其中多数为脂肪类化合物如十三烷、二十六碳醇等,此外还有黄酮类化合物如山奈酚、槲皮素,羧酸类如L-苹果酸、香豆素类如欧前胡素、秦皮乙素,萜类化合物和多酚类等成分。这些成分可能通过调节AKT1、CAMK2A、CAMK2B、CAMK2D,CAMK2G、CHRM1、GLP1R、PDE4A、PDE4B等39个靶蛋白,涉及环磷酸腺苷信号通路、阿尔茨海默病、胆碱能突触等21条信号通路发挥防治AD作用。结论:覆盆子防治AD可能与影响神经细胞胆碱能,影响细胞生长,抗细胞凋亡和抗神经炎性反应等机制有关,其物质基础可能是槲皮素、香草酸、阿魏酸、山奈酚、没食子酸、L-苹果酸、根皮素、欧前胡素。

Objective:Network pharmacology was used to explore the main material basis and mechanism of raspberry prevention and treatment of AD.Methods:Collect AD key therapeutic targets from Drugbank database and related literatures,and construct a raspberry chemical library using TCMSP data collection.Use Discovery Studio software to conduct molecular virtual docking,and screen out the set of chemical components in raspberries that bind to the key target of AD.Pathway enrichment analysis of these key targets was carried out by KEGG database to establish component-target-pathway relationship,and the component-target-pathway network diagram of raspberry was constructed by Cytoscape software.Results:Fifty ingredients were selected from raspberries,most of which were fatty compounds such as tridecane and 26-carbon alcohol.In addition,there are flavonoids such as citernol and quercetin,carboxylic acids such as l-malic acid,coumarins such as imperatorin,tetrahedrine,terpenes and polyphenols.These components may play a role in preventing AD by regulating 39 target proteins such as AKT1,CAMK2A,CAMK2B,CAMK2D,CAMK2G,CHRM1,GLP1R,PDE4A and PDE4B,which are involved in 21 signaling pathways such as cAMP signaling pathway,Alzheimer's disease and Cholinergic synapse.Conclusion:The prevention and treatment of AD in raspberry may be related to the mechanism of affecting cholinergic activity of nerve cells,affecting cell growth,antiapoptosis and anti-neuroinflammatory reaction,etc.The material basis of which may be quercetin,vanoxalic acid,ferulic acid,kaenefen,gallic acid,l-malic acid,phorin and imperatorin.