灵芝酸治疗阿尔茨海默病作用机制的网络药理学研究  

Mechanism of Action of Ganoderic Acid in Treatment of Alzheimer s Disease: A Study Based on Network Pharmacology

作　　者：覃云鹏 邵楠 叶树[2] 宋航 蔡标[2,3,4] QIN Yunpeng;SHAO Nan;YE Shu;SONG Hang;CAI Biao(School of Pharmacy,Anhui University of Chinese Medicine,Anhui Hefei 230012,China;School of Integrated Traditional Chinese and Western Medicine,Anhui University of Chinese Medicine,Anhui Hefei 230012,China;Institute of Integrated Traditional Chinese and Western Medicine,Anhui Academy of Chinese Medicine,Anhui Hefei 230012,China;Key Laboratory of Xin an Medicine,Ministry of Education,Anhui Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]安徽中医药大学中西医结合学院,安徽合肥230012 [3]安徽省中医药科学院中西医结合研究所,安徽合肥230012 [4]新安医学教育部重点实验室,安徽合肥230012

出　　处：《安徽中医药大学学报》2023年第6期65-72,共8页Journal of Anhui University of Chinese Medicine

基　　金：高校学科(专业)拔尖人才学术资助项目(gxbj2022024);安徽中医药大学2022年度第一批人才支持计划项目(2022rcyb028)。

摘　　要：目的 利用网络药理学技术确定灵芝酸治疗阿尔茨海默病(Alzheimer’s disease, AD)的相关靶点,探讨灵芝酸治疗AD的潜在机制。方法 采用Swiss Target Prediction药物靶点预测平台预测灵芝酸的靶点,并借助Disgenet数据库、Drugbank数据库和Genecards数据库检索AD的相关靶点;将化合物靶点与疾病靶点作交集得到灵芝酸作用于AD的潜在靶点。进一步使用STRING平台构建蛋白质相互作用(protein-protein interactions, PPI)网络,并通过网络拓扑分析筛选核心靶点;Bioconducter生物信息软件包对交集靶点进行GO与KEGG功能富集分析,筛选出灵芝酸与AD关联程度较高的信号通路。最后通过细胞实验,验证其中富集程度最高的靶点,进一步明确灵芝酸作用于AD的核心靶点。结果 从数据库中共获得灵芝酸与AD靶点1 211个,其中共同靶点56个。PPI网络拓扑分析发现,AKT1、ALB、MAPK3、CASP3、TNF等是灵芝酸治疗AD的关键靶点。KEGG通路富集分析结果显示,灵芝酸治疗AD的通路涉及AD、神经变性途径、人巨噬细胞感染途径、卡波西氏肉瘤相关疱疹病毒感染途径等。细胞实验验证发现,灵芝酸A的最佳给药浓度为50μmol/L,可以通过抑制p-PI3K和p-AKT的表达,保护受Aβ25-35毒性损伤的PC12细胞。结论 灵芝酸可能通过关键蛋白和重要通路达到靶向治疗AD的作用。Objective To investigate the potential mechanism of action of ganoderic acid in the treatment of Alzheimer s disease(AD)by identifying related targets based on network pharmacology.Methods The Swiss Target Prediction platform was used to predict the targets of ganoderic acid,and DisGeNET,DrugBank,and GeneCards databases were used to search for the targets related to AD;these two groups of targets were intersected to obtain the potential targets of ganoderic acid acting on AD.The STRING platform was used to construct a protein-protein interaction(PPI)network,and network topology was used to identify the core targets;Bioconductor bioinformatics software was used to perform GO and KEGG pathway enrichment analyses of the intersecting targets to screen for the signaling pathways with a relatively high degree of association with ganoderic acid and AD.A cell experiment was conducted to validate the targets with the highest degree of enrichment and further clarify the core targets of ganoderic acid acting on AD.Results A total of 1211 targets were obtained for ganoderic acid and AD in databases,among which there were 56 common targets.The PPI network topological analysis showed that the key targets of ganoderic acid in the treatment of AD included AKT1,ALB,MAPK3,CASP3,and TNF.The KEGG pathway enrichment analysis showed that the pathways of AD,neural degeneration,human macrophage infection,and Kaposi s sarcoma-related herpes virus were mainly involved in the treatment of AD by ganoderic acid.The cell experiment showed that at the optimal concentration of 50μmol/L,ganoderic acid A could protect PC12 cells against the injury caused by Aβ25-35 by inhibiting the expression of p-PI3Kand p-AKT.Conclusion Ganoderic acid exerts a targeted therapeutic effect on AD possibly by key proteins and important pathways.

关 键 词：灵芝酸 阿尔茨海默病 网络药理学 PI3K AKT 信号通路 

分 类 号：R285.5[医药卫生—中药学]