基于网络药理学探讨桃红四物汤治疗阿尔茨海默症的主要有效成分及其作用机制  

Exploring the main active components and potential mechanisms of Taohong Siwu Decoction for the treatment of Alzheimer's disease based on network pharmacology

作　　者：李双 孙璐瑶 尤斯涵 张佳燚 殷宏艳 曹津萌 刘心星 郭春燕[2,3,4] 刘喜富 Shuang Li;Luyao Sun;Sihan You;Jiayi Zhang;Hongyan Yin;Jinmeng Cao;Xinxing Liu;Chunyan Guo;Xifu Liu(Ministry of Education Key Laboratory of Molecular and Cellular Biology,Hebei Anti-Tumor Molecular Target Technology Innovation Center,College of Life Science,Hebei Normal University,Shijiazhuang 050024,Hebei,China;Department of Pharmacy,Hebei North University,Zhangjiakou 075000,Hebei,China;Jianyuan Precision Medicines(Zhangjiakou)Co.,Ltd.,Zhangjiakou 075000,Hebei,China;Hebei Key Laboratory of Neuropharmacology,Zhangjiakou 075000,Hebei,China)

机构地区：[1]河北师范大学生命科学学院,河北石家庄050024 [2]河北北方学院药学院,河北张家口075000 [3]张家口健垣精准医学有限公司,河北张家口075000 [4]河北省神经药理学重点实验室,河北张家口075000

出　　处：《Journal of Chinese Pharmaceutical Sciences》2024年第6期525-542,共18页中国药学（英文版）

基　　金：The Project of Hebei North University(Grant No.XJ2023041);the Natural Science Foundation of Hebei Province(Grant No.H2021405021);the S&T Program of Hebei(Grant No.V1623922326576)。

摘　　要：桃红四物汤(Taohong Siwu Decoction,THSWD)是活血化瘀的经典中药方剂,本研究利用网络药理学筛选THSWD潜在活性成分,探讨其治疗阿尔茨海默症的核心作用靶点和信号通路。首先,通过TCMSP和SEA数据库,筛选THSWD的活性成分及其作用靶点,共获得25个活性化合物(active compounds,ACs)和478个活性成分靶点;通过TTD、Dis Ge NET、Drug Bank、GAD和Gene Cards数据库共获得阿尔茨海默症疾病靶点724个。寻找活性成分作用靶点和疾病相关靶点的交集,共获得64个靶点(overlapping targets,OTs)。然后,构建25个ACs和64个OTs相互关系网络,获得21个一级关键化合物(first level key compound,FKCs)。通过对64个OTs进行PPI分析,获得33个核心靶点(core targets,CTs),并对这33个CTs进行KEGG聚类分析,获得排名靠前73条通路。最后,利用Cytoscape 3.7.2软件绘制“21个FKCs-33个CTs-73条通路”网络关系图,根据拓扑参数进行选择,进一步获得19个二级关键化合物(second key components,SKCs)。对“19个SKCs-33个CTs-73条通路”进行网络的分析与提取,最终构建得到THSWD干预阿尔茨海默症“6种单味药-8种潜在活性成分-13个核心作用靶点-54条信号通路”的网络图谱。研究结果为阐明THSWD的药效物质基础和进一步研究THSWD治疗阿尔茨海默症的作用机制和临床应用提供了新思路。Taohong Siwu Decoction(THSWD),a traditional Chinese prescription renowned for its efficacy in promoting blood circulation and alleviating blood stasis,was investigated in this study to delineate its potential active components and discern the core targets(CTs)and signaling pathways implicated in the treatment of Alzheimer's disease(AD).Initially,25 active compounds(ACs)and 478 corresponding active ingredient targets(AITs)of THSWD were meticulously identified by scrutinizing the active ingredients and their targets through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Similarity Ensemble Approach(SEA)databases.Subsequently,a comprehensive compilation of 724 AD-related targets was assembled from the Therapeutic Target Database(TTD),DisGeNET,DrugBank,Genetic Association Database(GAD),and GeneCards databases.Through a meticulous alignment of AITs with disease-related targets,64 overlapping targets(OTs)emerged as critical intersections.To distill the key compounds,an intricate analysis of the interrelationships among the 25 ACs and 64 OTs resulted in the identification of 21 first-level key compounds(FKCs).Further scrutiny through protein-protein interaction(PPI)analysis of the 64 OTs revealed 33 CTs.KEGG cluster analysis of these CTs yielded the top 73 pathways,forming the basis for constructing a network diagram encompassing"21 FKCs-33 CTs-73 pathways"using Cytoscape 3.7.2 software.Refining the network through the selection of topological parameters led to the identification of 19 second key components(SKCs).This information was then employed to construct a refined network,"19 SKCs-33 CTs-73 pathways",providing deeper insights into the intricate connections within the system.Further analyses culminated in the creation of a comprehensive network map,encapsulating"6 single drugs-8 potential active ingredients-13 core targets-54 signaling pathways",elucidating the multifaceted intervention of THSWD in AD.These results offered a novel perspective for understanding the pharmacodynamic material basis of

关 键 词：阿尔茨海默症 网络药理学 桃红四物汤 中医药 

分 类 号：R284[医药卫生—中药学]