基于网络药理学方法探究天麻素抗阿尔兹海默症的作用机制

Exploring the Mechanism of Action of Gastrodin against Alzheimer's Disease Based on Network Pharmacology

目的利用网络药理学方法探究天麻素抗阿尔兹海默症(alzheimer’s disease,AD)的作用机制。方法通过PhrmMapper平台预测天麻素的潜在靶点,检索GeneCards数据库中AD的靶点,取潜在靶点与疾病靶点的交集,作为天麻素抗AD的候选靶点。将候选靶点导入STRING数据库,绘制蛋白互作网络并进行分析,度值高的靶点作为天麻素抗AD的重要靶点。将候选靶点导入DAVID数据库进行基因功能注释和KEGG通路富集分析。结果经PhrmMapper预测和筛选后得到69个的潜在靶点,检索GeneCards数据库中得到AD相关靶点10972个,获得候选靶点共55个;蛋白互作网络包含ESR1、CASP3、HSPA8、CCNA2、LDHB、PLAU等44个蛋白。基因功能注释结果得到46个生物过程(BP)条目,8个分子功能(CC)条目,25个细胞组成(MF)条目。KEGG通路富集得到8条信号通路(P<0.05),包括氨基糖和核苷酸糖代谢、氮代谢、AMPK信号通路、胰岛素信号通路、淀粉和蔗糖代谢、半胱氨酸和蛋氨酸代谢、甲状腺激素信号通路、细胞周期。结论天麻素可能通过ESR1、CASP3、HSPA8、CCNA2、LDHB、PLAU等靶点,调控氨基糖和核苷酸糖代谢、氮代谢、AMPK信号通路、胰岛素信号通路、淀粉和蔗糖代谢、半胱氨酸和蛋氨酸代谢、甲状腺激素信号通路、细胞周期,发挥治疗AD的作用。

Objective:To explore the mechanism of action of gastrodin against Alzheimer's disease(AD)by network pharmacology.Methods:The potential targets of gastrodin were predicted by PhrmMapper platform,the AD targets in the GeneCards database were searched,and the intersection of potential targets and disease targets was taken as the candidate targets of gastrodin against AD.The candidate targets were imported into the STRING database,and the protein interaction network was drawn and analyzed.The candidate targets were imported into the DAVID database for gene function annotation and KEGG pathway enrichment analysis.Results:69 potential targets were predicted and screened by PhrmMapper,and 10972 AD-related targets were retrieved from the GeneCards database,and a total of 55 candidate targets were obtained.The protein interaction network included ESR1,CASP3,HSPA8,CCNA2,LDHB,PLAU and other 44 proteins.Gene function annotation results obtained 46 biological process(BP)entries,8 molecular function(CC)entries,and 25 cellular composition(MF)entries.KEGG pathway enrichment resulted in 8 signaling pathways(P<0.05),including amino sugar and nucleotide sugar metabolism,nitrogen metabolism,AMPK signaling pathway,insulin signaling pathway,starch and sucrose metabolism,cysteine and methionine metabolism,thyroid Hormone signaling pathways and cell cycle.Conclusion:Gastrodin may regulate amino sugar and nucleotide sugar metabolism,nitrogen metabolism,AMPK signaling pathway,insulin signaling pathway,starch and sucrose metabolism,cysteine and methionine metabolism,thyroid hormone signaling pathway and cell cycle through ESR1,CASP3,HSPA8,CCNA2,LDHB,PLAU and other targets and play a role in the treatment of AD.