医学分子生物学杂志2026，Vol.23Issue(3)：266-274,9.DOI:10.3870/j.issn.1672-8009.2026.03.005
月季花活性成分槲皮素抗烟曲霉的宿主-病原体通路互作机制研究
Mechanisms of Host-Pathogen Pathway Interactions Mediated by Quercetin Against Aspergillus fumigatus
摘要
Abstract
Objective To investigate the multi-target mechanism of quercetin,the main active component of Rosa chinensis(R.chinensis),against Aspergillus fumigatus(A.fumigatus)from the host-pathogen interaction perspective.Methods Firstly,the active components of R.chinensis and host targets related to A.fumigatus infection were screened using TCMSP,GeneCards,and OMIM databases.Virulence and drug resistance-related targets of A.fumigatus were obtained from NCBI and UniProt databases.Cross-species homology mapping was performed using the KEGG Orthology sys-tem,and a Host-Pathogen Pathway Interaction Network(HPPIN)was constructed using Cytoscape 3.10.3.Core targets were identified through topological analysis(degree centrality and betweenness centrality).Secondly,molecular docking of quercetin with the core targets was conducted using AutoDock Vina 1.5.7,with a binding energy threshold of≤-5.0 kcal/mol.The optimal complex was selected for a 100 ns molecular dynamics simulation using GROMACS 2020.6(AMBER99SB force field)to analyze binding stability via root-mean-square deviation(RMSD),root-mean-square fluctuation(RMSF),and hydrogen bond numbers.Finally,following the CLSI M38-A3 protocol,the minimum inhibitory concentration(MIC)of quercetin against the standard A.fumigatus strain Af293 was determined using the broth microdilution method.Phenotypic rescue experiments using a mixture of N-acetylcysteine and purine were performed to validate the predicted interference with oxidative stress and purine metabolism pathways,and hyphal morphological chan-ges were observed under an inverted microscope.Results The HPPIN identified 12 key tar-gets.Quercetin exhibited binding energies of-7.6 kcal/mol with KRas and-7.8 kcal/mol with SA-ICAR synthetase,forming stable complexes(RMSD<0.2 nm).The MIC of quercetin against A.fumigatus was 256 μg/mL,resulting in complete inhibition of hyphal growth.This inhibitory effect was reversed by N-acetylcysteine,confirming the role of oxidative stress.Concurrently,com-bination with high-concentration purine led to complete germination failure,indicating disruption of purine metabolism.Conclusion Quercetin synergistically inhibits A.fumigatus through dual mecha-nisms of"starvation"and"intoxication."关键词
宿主-病原体互作/烟曲霉/网络药理学/分子对接/分子动力学/槲皮素/月季花Key words
host-pathogen interaction/Aspergillus fumigatus/network pharmacology/molec-ular docking/molecular dynamics/quercetin/Rosa chinensis分类
医药卫生引用本文复制引用
高小喻,马彦..月季花活性成分槲皮素抗烟曲霉的宿主-病原体通路互作机制研究[J].医学分子生物学杂志,2026,23(3):266-274,9.基金项目
山西省基础研究计划自然科学项目面上研究项目(No.202103021224416) This work was supported by a grant from the Natural Science Research Project of Basic Research Plan in Shanxi Province(No.202103021224416) （No.202103021224416）
