安徽医科大学学报2026,Vol.61Issue(4):618-627,10.DOI:10.19405/j.cnki.issn1000-1492.2026.04.005
基于网络药理学和细胞实验探讨肉豆蔻对动脉粥样硬化的作用机制
Integrated network pharmacology analysis and cellular evidence reveal the mechanisms of Myristica fragrans against atherosclerosis
摘要
Abstract
Objective To explore the potential mechanisms by which Myristica fragrans prevents and treats athero-sclerosis(AS).Methods The major active components of Myristica fragrans and their shared targets with AS were obtained from databases.The shared targets were subjected to pathway enrichment analysis and PPI network con-struction using the ClusterProfile package and the STRING database.Molecular docking between key targets and major active components was performed using AutoDock.Gene expression data from early and late,as well as stable and unstable AS plaques,were used to validate changes of key targets and major pathways during AS pro-gression.Western blot,flow cytometry,YO-PRO-1/PI staining,and TUNEL staining were applied to verify the main mechanisms.Results Nine active components of Myristica fragrans interacted with 293 AS-related targets,among which eight components acted on an average of 57.0%of the shared targets.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that the anti-AS effects mainly in-volved oxidative stress,inflammation,lipid metabolism,fluid shear stress,and apoptosis pathways.PPI network revealed JUN,CASP3,MAPK3,and AKT1 as key targets mainly involved in regulating apoptosis.Molecular dock-ing showed stable binding conformations and high affinities between major components and these targets.Inte-grated analysis of gene expression in early and late,as well as stable and unstable AS plaques,showed significant enrichment of leukocyte apoptosis pathways in late and unstable plaques.Cell experiments further confirmed that Myristica fragrans significantly reduced Cleaved-CASP3(P=0.04)and p-MAPK3(P=0.000 3)levels,increased p-AKT1(P=0.004)levels,and inhibited macrophage apoptosis.Conclusion Myristica fragrans potentially inter-feres with AS development by modulating pathways related to oxidative stress,inflammation,lipid metabolism,fluid shear stress,and apoptosis,with CASP3,MAPK3,and AKT1 serving as key targets mediating its anti-apoptotic and anti-AS effects.关键词
肉豆蔻/动脉粥样硬化/网络药理学/分子对接分析/巨噬细胞凋亡Key words
Myristica fragrans/atherosclerosis/network pharmacology/molecular docking analysis/macro-phage apoptosis分类
医药卫生引用本文复制引用
卢淑娴,周志玲,张弋峰,余军..基于网络药理学和细胞实验探讨肉豆蔻对动脉粥样硬化的作用机制[J].安徽医科大学学报,2026,61(4):618-627,10.基金项目
江西省科技专项资金项目(编号:20232BAB216012) (编号:20232BAB216012)
江西省大学生创新创业训练计划项目(编号:S202310412091) Special Fund for Science and Technology of Jiangxi Province(No.20232BAB216012) (编号:S202310412091)
College Student Innovation and Entrepreneurship Training Project of Jiangxi Province(No.S202310412091) (No.S202310412091)