基于网络药理学和分子对接技术研究人参皂苷Rg1治疗阿尔茨海默病的分子生物学机制  

Molecular Biological Mechanisms of Ginsenoside Rg1 in Treating AD Based on Network Pharmacology and Molecular Docking Technology

作　　者：盛望[1] 王瑾茜 殷淑婷 李旭华[1] 胡国恒[1,2] 谢丽华[1,2] SHENG Wang;WANG Jinxi;YIN Shuting;LI Xuhua;HU Guoheng;XIE Lihua(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学第一附属医院,湖南长沙410007 [2]湖南中医药大学,湖南长沙410208

出　　处：《中医药学报》2020年第12期54-60,共7页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金项目(81573941);湖南中医药大学校级科研基金项目(2018XJJJ 43)。

摘　　要：目的:基于网络药理学和分子对接技术分析人参皂苷Rg1治疗阿尔茨海默病(Alzheimer’s disease,AD)的分子生物学机制。方法:利用TCMSP、PharmMapper、Uniprot数据库筛选出人参皂苷Rg1的作用靶点,利用GeneCards、CTD数据库筛选AD相关靶点,对靶点进行PPI网络构建、GO富集、KEGG通路注释分析。采用AutoDock分子对接软件进行分子对接来预测人参皂苷Rg1对AD作用靶点的结合活性。结果:筛选出人参皂苷Rg1潜在靶点有203个,与AD相关的靶点有45个,GO富集结果显示生物过程有42个条目、分子功能有24个条目、细胞成分有14个条目,KEGG通路注释分析共分析出78条信号转导通路,包括雌激素信号通路、跨膜酪氨酸激酶信号通路、FoxO信号通路、肿瘤坏死因子信号通路等。结论:人参皂苷Rg1可能通过作用于CTSB、BCHE、AKT1等45个与AD相关的潜在靶点,调节细胞自噬、保护神经元、营养神经、抑制细胞凋亡、减少炎症反应、抗氧化应激、改善脑代谢等多种途径以减少Aβ的积累、抑制tau蛋白累积及异常磷酸化、减轻内皮细胞及神经元损伤发挥改善AD症状的作用。Objective:To investigate the molecular biological mechanism of ginsenoside Rg1 in the treatment of Alzheimer’s disease(AD)based on network pharmacology and molecular docking.Methods:The targets of ginsenoside Rg1 were determined by databases of TCMSP,PharmMapper and Uniprot,AD-related targets were selected by databases of GeneCards and CTD.The targets were structured by protein-protein interaction(PPI)network picture and analyzed by gene ontology(GO)and KEGG pathway.The binding of targets that ginsenoside Rg1 acted on AD was predicted based on the AutoDock molecular docking software.Results:There were 203 potential targets of ginsenoside Rg1 and 45 targets of AD.The 42 biological process,24 molecular function and 14 cellular component were obtained by GO analysis.78 signal pathways were obtained by KEGG pathway analysis,which included estrogen signaling pathway,ErbB signaling pathway,FoxO signaling pathway and TNF signaling pathway.Conclusion:Ginsenoside Rg1 may play a role in improving AD by regulating 45 AD-related targets,such as CTSB,BCHE,AKT1 and other targets to regulate autophagy,protect neurons,nourish nerves,inhibit apoptosis,reduce inflammatory response and oxidative stress,improve brain metabolism,resulting in reducing accumulation of Aβ,inhibiting tau protein accumulation and abnormal phosphorylation,alleviating endothelial cells and neuronal damage.

关 键 词：阿尔茨海默病 人参皂苷RG1 网络药理学 分子对接 

分 类 号：R277.7[医药卫生—中医学] R741