基于网络药理学和分子对接探讨肉豆蔻治疗心肌缺血的作用机制  

Exploring the mechanism of action of Myristica fragrans houtt in the treatment of myocardial ischemia based on network pharmacology and molecular docking

作　　者：杜广朋 孙洪涛[1] DU Guangpeng;SUN Hongtao(School of Clinical Medicine,Affiliated Hospital of Inner Mongolia Minzu University,Tongliao,Inner Mongolia 028000,China;Department of Cardiology,the First Rehabilitation Hospital of Shandong,Linyi,Shandong 276032,China)

机构地区：[1]内蒙古民族大学临床医学院,内蒙古通辽028000 [2]山东省第一康复医院心内科,山东临沂276032

出　　处：《现代医药卫生》2024年第23期3993-4000,共8页Journal of Modern Medicine & Health

摘　　要：目的采用网络药理学和分子对接探索蒙药肉豆蔻治疗心肌缺血(MI)的作用机制。方法通过中药系统药理学数据库、PubChem、SwissTargetPrediction等数据库检索得到肉豆蔻的主要化学成分及作用靶点。人类基因组数据库、在线人类孟德尔遗传数据系统、药物靶点数据库获得与MI相关的蛋白靶点,使用微生信构建肉豆蔻活性成分-MI相交靶点网络,String数据库构建肉豆蔻蛋白质相互作用网络并进行可视化分析,DAVID数据库进行基因本体富集分析及京都基因与基因组百科全书通路分析,运用AutoDock Vina软件进行分子对接计算验证,Pymol软件将对接结果可视化,预测其作用机制。结果最终获得肉豆蔻9种药物活性成分的潜在靶点和与MI相关的195个相交靶点基因,AKT1、清蛋白、表皮生长因子受体、ESR1、SRC等可能是重要的治疗靶点。肉豆蔻在对抗MI中涵盖了细胞代谢调控、细胞死亡现象,如细胞凋亡及细胞周期的动态平衡等生物过程,可能通过调节包括FoxO信号通路、ErbB信号通路、TRP通道的炎症介质调节、磷酸肌醇-3激酶/蛋白激酶B信号通路等治疗MI。分子对接结果显示,核心成分与核心靶点具有较好的结合能。结论肉豆蔻可能通过多成分、多靶点、多通路方式实现对MI损伤的有效干预与保护。Objective To explore the mechanism of action of the Mongolian drug,Myristica fragrans houtt,in the treatment of myocardial ischemia(MI)using network pharmacology and molecular docking.Methods The main chemical components and targets of Myristica fragrans houtt were obtained by searching the TCM systematic pharmacology database,PubChem,SwissTargetPrediction and other databases.The human genome database,online human Mendelian genetic data system,and drug target database were used to obtain protein targets related to MI,microbiotics letter was used to construct Myristica fragrans houtt active ingredient-MI intersecting target network,String database was used to construct Myristica fragrans houtt protein interactions network and visualized,DAVID database was used to perform gene ontology enrichment analysis and Kyoto gene and genome encyclopedia pathway analysis.AutoDock Vina software was used to validate the molecular docking calculations,and Pymol software was used to visualize the docking results and predict the mechanism of action.Results The potential targets of nine pharmacologically active components of Myristica fragrans houtt and 195 intersecting target genes related to MI were finally obtained,and AKT1,clearin,epidermal growth factor receptor,ESR1 and SRC may be important therapeutic targets.Myristica fragrans houtt in the fight against MI covers the regulation of cell metabolism,cell death phenomena,such as apoptosis and the dynamic balance of the cell cycle,and other biological processes,and may be used to treat MI by modulating the regulation of inflammatory mediators including the FoxO signaling pathway,the ErbB signaling pathway,the TRP channel,and the phosphatidylinositol-3 kinase/protein kinase B signaling pathway.The results of the molecular docking showed that the core components and the core targets had a better binding energy.Conclusion Myristica fragrans houtt may achieve effective intervention and protection against MI injury through a multi-component,multi-target,multi-pathway approach.

关 键 词：肉豆蔻 心肌缺血 治疗 网络药理学 分子对接 作用机制 

分 类 号：R282.71[医药卫生—中药学] R285[医药卫生—中医学]