探讨防己生物碱成分防治阿尔茨海默病的作用机制——基于网络药理学和分子对接  

Study on the Mechanisms of Alkaloid Components in the Root of Stephania Tetrandra in Preventing and Treating Alzheimer′s Disease——Based on Network Pharmacology and Molecular Docking

作　　者：孟雪莲[1] 张靖 MENG Xue-lian;ZHANG Jing(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)》2024年第4期315-326,共12页Journal of Liaoning University:Natural Sciences Edition

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

摘　　要：本文基于网络药理学和分子对接的方法探究防己中主要生物碱成分防治阿尔茨海默病(Alzheimer′s disease,AD)的作用机制.在中药系统药理学数据库与分析平行(TCMSP)数据库中进行检索得到防己中主要生物碱成分共6种,在Swiss Target Prediction和Disgenet数据库检索得到生物碱和AD的相关靶点,在Venny 2.1.0平台中获得交集靶点,运用STRING数据库绘制蛋白质相互作用网络.通过DAVID数据库进行京都基因与基因组百科全书(KEGG)通路分析,在Cytoscape 3.9.0软件中绘制“药物成分-作用通路-作用靶点-疾病”网络.将生物碱成分与抗AD主要靶点蛋白结果导入到Discovery Studio软件进行分子对接验证.研究结果表明,防己中6种主要生物碱成分与AD的47个核心靶点相关,可能通过34条相关作用通路发挥作用.其中度值较大的生物碱成分包括木兰花碱、蝙蝠葛任碱、粉防己碱等;关键作用靶点有丝裂原活化蛋白激酶1(MAPK1)、丝裂原激活蛋白激酶激酶1(MAP2K1)、蛋白激酶B1(AKT1)等;主要的作用通路包括丝裂原活化蛋白激酶信号通路、神经活性配体-受体相互作用通路、钙离子信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路等.以上结果表明,防己中主要生物碱成分在防治AD方面具有“多成分、多靶点、多途径”的特点,为未来研究防己中主要生物碱成分防治AD的作用机制提供了理论基础.In this paper,based on network pharmacology and molecular docking methods,it explored the mechanism of the main alkaloid components in the root of Stephania tetrandra against Alzheimer′s disease(AD).A total of 6 main alkaloid components were searched in the pharmacology database and analysis platform of traditional Chinese medicine system(TCMSP).The related targets of alkaloids and AD were found in Swiss Target Prediction databases and Disgenet databases.The intersection targets were obtained in Venny 2.1.0 platform,and the protein interaction network was drawn by STRING database.The Kyoto encyclopedia of genes and genomes(KEGG)pathway was analyzed by DAVID database,and the“component-action pathway-action target-disease”network was drawn in Cytoscape 3.9.0 software.Discovery Studio software was used to verify the molecular docking results of six alkaloid components and the main target proteins of anti-AD.The results showed that the main 6 alkaloid components in the root of Stephania tetrandra were related to 47 core targets of AD,and may play a role through 34 related pathways.Among them,the alkaloid components with large degrees include Magnoflorine,Tetrandrine,Menisperine,etc.Key targets include mitogen-activated protein kinase 1(MAPK1),mitogen-activated protein kinase kinase 1(MAP2K1),serine/threonine kinase 1(AKT1),etc.The main pathways include MAPK1 signaling pathway,calcium signaling pathway,phosphoinositide 3-kinase-Akt(PI3K-Akt)signaling pathway,neuroactive ligand-receptor interaction,etc.The above results show that the main alkaloid components in the root of Stephania tetrandra have the characteristics of“multi-component,multi-target and multi-pathway”in the prevention and treatment of AD,which provides a theoretical basis for future research on the mechanism of the main alkaloid components in the root of Stephania tetrandra in the prevention and treatment of AD.

关 键 词：网络药理学 分子对接 防己生物碱成分 阿尔茨海默病 

分 类 号：R964[医药卫生—药理学]