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基于网络药理学探究黄精抗阿尔兹海默症作用机制

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为了从多成分、多靶点、多通路的角度探究黄精治疗阿尔兹海默症的潜在作用机制,从TCMSP数据库检索黄精的活性成分以及对应的作用靶点,并且在GeneCards数据库中以"Alzheimer's disease"为关键词检索阿尔兹海默症的相关靶点.将检索到的2类靶点相互映射得到交集靶点,通过STRING平台构建交集靶点的蛋白-蛋白相互作用(PPI)网络,依据degree值选取PPI网络中的核心靶点并在Cytoscape3.8中进行可视化分析.借助David 6.8数据库,对交集靶点进行GO与KEGG富集分析.最后使用Schrodinger软件对核心靶点与关键活性成分进行分子对接验证.结果显示:①从黄精中筛选出了黄芩素、β-谷甾醇和甘草素3个关键活性成分,从GeneCards数据库中筛选出了阿尔兹海默症的3个核心靶点,即AKT1、CASP3和TP53;②GO与KEGG富集分析发现,靶点多集中于癌症通路、细胞凋亡以及PI3K-Akt信号通路;③ 依据分子对接部分的对接分数判断出黄芩素和甘草素与AKT1和TP53的对接效果更好.以上结果表明,黄精中的有效成分黄芩素和甘草素更有可能靶向AKT1和TP53,并通过调节细胞凋亡以及PI3K-Akt等信号通路达到抗阿尔兹海默症的效果.
Exploration of the mechanism of Huangjing in the treatment of Alzheimer's disease based on network pharmacology
In order to explore the potential mechanism of action of Huangjing in treating Alzheimer's disease from the perspec-tive of multi-component,multi-target and multi-pathway,the active components and the corresponding targets of Huangjing were retrieved from TCMSP database,and related targets of Alzheimer's disease were retrieved from GeneCards database using"Alzheimer's disease"as the keyword.The intersection targets were obtained by mapping the two types of targets retrieved to each other.A Protein-Protein Interaction(PPI)network with intersection targets was constructed through the STRING platform.The core targets in PPI network were selected according to degree values and were visualized in Cytoscape3.8.The GO and KEGG enrichment analyses were performed for intersection targets using David 6.8 database.Finally,Schrodinger software was used to verify the molecular docking between the core targets and the key active ingredients.The results showed that:① Three key active components including Baicalein,β-sitosterol and Liquiritigenin were screened from Huangjing.Three core targets of Alzheimer's disease,namely AKT1,CASP3 and TP53 were selected from GeneCards database;② GO and KEGG enrichment analysis showed that the targets were mainly concentrated in cancer pathway,apoptosis and PI3K-Akt signaling pathway;③ According to the docking score of molecular docking,it can be showed that Baicalin and Liquiritigenin had better docking effect with AKT1 and TP53.These results indicated that Baicalein and Liquiritigenin were more likely to target AKT1 and TP53,and they can achieve anti-Alzheimer's effect by regulating apoptosis and P13K-Akt signaling pathway.

HuangjingAlzheimer's diseasenetwork pharmacologymechanism of actionmolecular docking

贾子贤、史丽颖、刘紫琳、温泽宇、于大永

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大连大学 生命健康学院,辽宁 大连 116622

承德医学院 基础医学院,河北 承德 067000

黄精 阿尔兹海默症 网络药理学 作用机制 分子对接

2024

天津师范大学学报(自然科学版)
天津师范大学

天津师范大学学报(自然科学版)

CSTPCD北大核心
影响因子:0.311
ISSN:1671-1114
年,卷(期):2024.44(6)