基于网络药理学研究莲子心化学成分防治阿尔茨海默病的作用机制  

Study on the Mechanisms of Chemical Components for Lotus(Nelumbo nucifera Gaertn.)Seed Embryo in Preventing and Treating Alzheimer′s Disease Based on Network Pharmacology

作　　者：孟雪莲[1] 刘晓娜 张欣 陈长兰[1] MENG Xue-lian;LIU Xiao-na;ZHANG Xin;CHEN Chang-lan(School of Pharmaceutical Sciences,Liaoning University,Shenyang 110036,China)

机构地区：[1]辽宁大学药学院,辽宁沈阳110036

出　　处：《辽宁大学学报（自然科学版）》2021年第4期289-299,共11页Journal of Liaoning University：Natural Sciences Edition

基　　金：国家自然科学基金项目(81503085);辽宁省教育厅基础研究项目(LJC202008);2020年度省级“大学生创新创业”项目(D201911242232078260)。

摘　　要：该研究基于网络药理学分析了莲子心化学成分防治阿尔茨海默病的作用机制.首先,在TCMSP、BATMAN-TCM数据库中检索莲子心的化学成分,经筛选得到13种主要活性成分.利用Swiss Target Prediction数据库预测得到上述莲子心主要活性成分的潜在作用靶点有95个.其次,在Gene Cards数据库中查找与阿尔茨海默病相关的基因靶点,并利用Venny2.1.0软件,取莲子心化学成分与阿尔茨海默病靶点两者交集,得到“药物成分-疾病”交集靶点73个.利用String数据库,构建交集靶点蛋白相互作用(PPI)网络图,经分析发现GRM2、HDAC1、CHRNB4、CHRNB2为莲子心药效成分抗阿尔茨海默病作用关键靶点蛋白.最后,在DAVID数据库中通过KEGG分析,富集到莲子心化学成分潜在作用靶点相关的信号通路,并利用Cytoscape 3.7.2软件构建了“药物成分-交集靶点-作用通路”网络模型图,结果表明,莲子心的13个活性化合物与50个阿尔茨海默病关键核心靶标相关,参与调节的关键信号通路有11条.其中,度值较大的化学成分有甲基莲心碱、莲心碱、异莲心碱等;度值较大的靶点蛋白有DRD1(多巴胺受体D1)、DRD2(多巴胺受体D2)、DRD5(多巴胺受体D5)等;主要涉及的通路有神经活动配体-受体相互作用通路、5-羟色胺能突触信号通路、钙离子信号通路、多巴胺能突触信号通路等.上述结果为进一步探讨莲子心化学成分防治阿尔茨海默病的药效物质基础和作用机制提供了理论依据.Based on network pharmacology,the present study analyzed the pharmacological mechanism of the chemical components in lotus(Nelumbo nucifera Gaertn.)seed embryo in the prevention and treatment of Alzheimer′s disease.Firstly,the chemical components of lotus seed embryo were searched in TCMSP and BATMAN-TCM databases,and 13 main active components were obtained.By using Swiss Target Prediction database,a total of 95 potential targets for the above-mentioned active components of lotus seed embryo were predicted.Then,the gene targets related to Alzheimer′s disease were found in Gene Cards database.The intersection of chemical components of lotus seed embryo and Alzheimer′s disease targets was obtained by using Venny2.1.0 software,and 73 intersection targets of“drug component-disease”were obtained.By using String database,the protein-protein interaction(PPI)diagram was constructed.The results showed that GRM2,HDAC1,CHRNB4,and CHRNB2 were the key target proteins of the components of lotus seed embryo in anti-Alzheimer′s disease.Finally,by KEGG analysis in DAVID database,the signal pathways related to potential targets of chemical components in lotus seed embryo were enriched,and then the network model diagram of“drug component-intersection target-pathway”was constructed by using Cytoscape 3.7.2 software.The results showed that 13 active compounds in lotus seed embryo were related to 50 key targets of Alzheimer′s disease,and 11 key signal pathways were involved in the regulation.Among them,neferine,liensinine and isoliensinine are the chemical components with higher degree value;DRD1(Dopamine D1 receptor),DRD2(Dopamine D2 receptor)and DRD5(Dopamine D5 receptor)are the target proteins with higher degree;the main pathways involved are neuroactive ligand-receptor interaction,serotonergic synapse,calcium signaling pathway,dopaminergic synapse and so on.These results provide a theoretical basis for further study on the pharmacodynamic material basis and mechanism of chemical components in lotus seed embryo in

关 键 词：莲子心 阿尔茨海默病 网络药理学 

分 类 号：R967[医药卫生—药理学]