巴戟天-淫羊藿药对防治老年痴呆作用机制的网络药理学分析  

Study on Mechanism of Morindae officinalis Radix-Epimedii Folium Herb Pair in The Treatment of Senile Dementia Based on Network Pharmacology

作　　者：邓少东 丁晨 王颖 叶锦崇 郭上诗 黄嘉琪 叶海仪 DENG Shaodong;DING Chen;WANG Ying;YE Jinchong;GUO Shangshi;HUANG Jiaqi;YE Haiyi(Scientific Research Platform,The Second Clinical Medical College,Guangdong Medical University,Dongguan 523808 Guangdong,China;Department of Traditional Chinese Medicine,The Second Clinical Medical College,Guangdong Medical University,Dongguan 523808 Guangdong,China;School of Pharmacy,Guangdong Medical University,Dongguan 523808 Guangdong,China)

机构地区：[1]广东医科大学第二临床医学院科研平台,广东东莞523808 [2]广东医科大学第二临床医学院中医学教研室,广东东莞523808 [3]广东医科大学药学院,广东东莞523808

出　　处：《中药新药与临床药理》2021年第7期988-997,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81403085);广东省中医药局资助项目(20191189);广东省“扬帆计划”引进紧缺拔尖人才项目(4YF16001G);广东医科大学引进人才科研启动基金项目(2XB17028);广东医科大学校级大学生创新创业训练计划项目(GDMU2018095);广东省2019年度省级大学生创新创业训练计划项目(201910571095)。

摘　　要：目的基于网络药理学方法探讨巴戟天-淫羊藿药对防治老年痴呆的潜在分子作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP数据库)收集巴戟天、淫羊藿的化学成分,根据口服生物利用度、类药性、血脑屏障透过率等参数以及结合文献报道筛选其活性成分并预测其作用靶点;通过GeneCard、TTD、DiGSeE等数据库筛选出老年痴呆症相关的疾病靶点,并与活性成分作用靶点取交集即为药物与疾病的共同作用靶点;采用Cytoscape 3.7.1软件构建巴戟天-淫羊藿药对活性成分-共同作用靶点的可视化网络;基于STRING数据库,构建巴戟天-淫羊藿药对防治老年性痴呆靶点(共同作用靶点)的蛋白互作网络,根据拓扑学参数分析筛选出核心靶点;对共同作用靶点进行GO功能富集分析和KEGG信号通路富集分析,构建巴戟天-淫羊藿药对治疗老年痴呆症的"活性成分-共同作用靶点-信号通路"网络。结果共筛选出活性成分27个,获得"巴戟天-淫羊藿"药对与老年痴呆症的共同作用靶点129个;核心靶点涉及GAPDH、VEGFA、STAT3、SRC、EGFR、JUN、MAPK8等;GO富集分析得到生物学过程相关条目388条、分子功能相关条目131条及细胞组分相关条目117条(P<0.01);KEGG通路富集分析得到128条信号通路(P<0.01),其中筛选得到与老年痴呆相关的信号通路9条。结论巴戟天-淫羊藿药对防治老年痴呆症具有多成分、多靶点、多通路的作用特点,其作用机制可能与神经活性配体-受体相互作用、内分泌抵抗、5-羟色胺能突触、胆碱能突触、多巴胺能神经突触等信号通路相关。Objective To explore the molecular mechanism of Morindae officinalis radix-Epimedii folium herb pair for treatment of senile dementia based on network pharmacology.Methods The chemical components of Morindae officinalis radix and Epimedii folium were collected by using TCMSP database and references,and the parameters such as oral bioavailability,drug-likeness and blood brain barrier were screened.All targets of senile dementia were collected in GeneCard,TTD and DiGSeE databases.The common targets of chemical components and the senile dementia were figured out and Cytoscape 3.7.1 software was used to construct a visual network topological relationship map of the Constituent-Target,and analyze the protein-protein interaction network based on string database.The core targets of Morindae officinalis radix-Epimedii folium herb pair for senile dementia were selected based on topological parameters.Finally,the enrichment analysis of gene ontology(GO)and KEGG pathway enrichment analysis were carried out,and the network of Constituent-Target-Signaling pathway was constructed.Results Twenty-seven active constituents of Morindae officinalis radix-Epimedii folium herb pair were screened out and 129 related targets of them were obtained which could act on senile dementia.The core targets are GAPDH,VEGFA,STAT3,SRC,EGFR,JUN,MAPK8,and so on.In the results of GO enrichment analysis,there are 388 GO terms related to biological process,131 GO terms related to molecular function,and 117 GO terms related to cellular component(P<0.01).The KEGG pathway enrichment analysis contains 128 pathways(P<0.01),among which nine signaling pathways related to senile dementia were screened.Conclusion Morindae officinalis radix-Epimedii folium herb pair has the characteristics of multi-constituent,multi-target,and multi-pathway action in the treatment of senile dementia,and neuroactive ligand-receptor interaction,endocrine resistance,serotonergic synapse,and cholinergic synapse may play important roles in senile dementia treated by Morindae officina

关 键 词：巴戟天 淫羊藿 药对 老年痴呆症 网络药理学 作用机制 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]