基于网络药理学分析北豆根抗阿尔茨海默病的作用机制  

Analysis of the Mechanisms of Menispermum Rhizoma Against Alzheimer′s Disease Based on Network Pharmacology

作　　者：孟雪莲[1] 刘松瑶 薛京苏 MENG Xue-lian;LIU Song-yao;XUE Jing-su(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）》2022年第4期343-354,共12页Journal of Liaoning University：Natural Sciences Edition

基　　金：辽宁省教育厅基础研究项目(LJC202008);辽宁省科技厅自然科学基金项目(2021-MS-155)。

摘　　要：本文基于网络药理学方法分析了北豆根抗阿尔茨海默病(AD)的作用机制,应用TCMSP、BATMAN-TCM数据库筛选北豆根中主要活性成分,并用SwissTargetPrediction数据库分析预测其潜在的作用靶点,应用GeneCards、OMIM数据库检索与AD有关的基因靶点,利用BioVenn软件获取北豆根活性成分靶点与AD靶点的交集,得到“药物成分-疾病”交集靶点.本文通过string数据库构建了靶点蛋白的相互作用(PPI)网络图,进一步采用David数据库来进行GO富集分析和KEGG通路富集分析,应用Cytoscape 3.7.2软件构建了“药物成分-交集靶点-疾病”网络模型图和“药物成分-交集靶点-作用通路”网络模型图,最终利用分子对接进行验证.研究结果表明,北豆根中7个主要活性成分与69个AD关键核心靶标相关,主要参与调节的信号通路有31条.度值较大的药物活性成分有粉防己碱、蝙蝠葛啡诺林碱、蝙蝠葛碱等;关键作用靶点蛋白有蛋白激酶Bα(AKT1)、磷脂酰肌醇-3-激酶催化亚基α(PIK3CA)、磷脂酰肌醇3-激酶催化亚基δ(PIK3CD)、磷脂酰肌醇3-激酶调节亚基(PIK3R1)等;主要参与的作用通路有磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路、大鼠肉瘤(Ras)信号通路、端粒结合蛋白(Rap1)信号通路等.上述结果提示了北豆根具有“多成分-多靶点-多通路”调控AD的作用特点,为进一步探讨北豆根干预AD作用机制提供理论依据.The mechanisms of Menispermum Rhizoma in the treatment of Alzheimer′s disease(AD)was analyzed based on network pharmacology.The main effective components of Menispermum Rhizoma were obtained by TCMSP database, BATMAN-TCM database respectively, and their potential targets were predicted by SwissTargetPrediction database.The gene targets related to AD were founded in GeneCards database and OMIM database.The “drug component-disease” intersection targets of active components targets and AD targets were obtained by BioVenn software.String database was used to constructed the protein-protein interaction(PPI)network diagram, and David database was used for GO enrichment analysis and KEGG enrichment analysis.Cytoscape 3.7.2 software was used to obtain “drug component-intersection target-disease” network model diagram and “drug component-intersection target-pathway” network model diagram, and it was verified by molecular docking.The results showed that 7 main active compounds in Menispermum Rhizomaare related to 69 key targets of AD,and 31 key signal pathways are involved in regulation.Tetrandrine, Dauriporphinoline and Dauricine are the drug active components with higher degree value;AKT1,PIK3CA,PIK3CD and PIK3R1 are the key target proteins;the main pathways involved are PI3K-Akt signaling pathway, Ras signaling pathway, Rap 1 signaling pathway and so on.These results suggest that Menispermum Rhizoma has the characteristics of “multiple components, multiple targets, and multiple pathways” regulation of AD,and provide a theoretical basis for further study on the mechanisms of Menispermum Rhizoma intervention in AD.

关 键 词：网络药理学 北豆根 阿尔茨海默病 

分 类 号：R96[医药卫生—药理学]