中国比较医学杂志2025，Vol.35Issue(12)：1-12,12.DOI:10.3969/j.issn.1671-7856.2025.12.001
基于网络药理学、分子对接与实验验证探讨熊果酸治疗矽肺纤维化的作用机制
Exploring the mechanism of ursolic acid in the treatment of silicosis fibrosis based on network pharmacology,molecular docking,and experimental validation
摘要
Abstract
Objective To explore the therapeutic mechanism of ursolic acid against silicosis fibrosis based on network pharmacology,molecular docking and in vitro experiments.Methods Ursolic acid targets were obtained from databases,including GeneCards and PubChem.Disease-related databases(GeneCards,OMIM)were searched for targets related to silicosis fibrosis and epithelial-mesenchymal transition(EMT).A micro-biotech platform was used to screen for intersecting targets,and a protein-protein interaction network was constructed using the STRING database and Cytoscape to screen the core targets.The David database was used for GO and KEGG enrichment analysis.AutoDock was used for molecular docking validation.Key targets were validated using beas-2B cells.Results We obtained 179 ursolic acid targets,8023 silicosis fibrosis targets,6809 EMT-related targets,and 133 intersecting targets.Nine core targets,including AKT,STAT3,and MMP9,were identified,among which MMP9 and AKT had the highest connectivity in the protein-protein interaction network.Molecular docking showed that ursolic acid had strong binding activity with MMP9(binding energy-8.4 kJ/mol)and AKT(binding energy-7.9 kJ/mol).KEGG analysis indicated the PI3K-AKT signaling pathway to be a key regulatory pathway.In vitro experiments showed that ursolic acid significantly inhibited the decrease in cell viability induced by SiO2(CCK8).Ursolic acid also reduced p-AKT expression(Western blot,P＜0.05);downregulated expression of the fibrosis marker α-SMA and the mesenchymal marker Vimentin,while upregulated expression of the epithelial marker E-cadherin(immunofluorescence/Western blot,P＜0.05).Conclusions Ursolic acid may play an anti-silicosis fibrosis role by inhibiting AKT phosphorylation,reducing MMP9 levels and regulating EMT.关键词
熊果酸/矽肺纤维化/PI3K-AKT信号通路/上皮-间质转化/分子对接Key words
ursolic acid/silicosis fibrosis/PI3K-AKT signaling pathway/epithelial-mesenchymal transition/molecular docking分类
医药卫生引用本文复制引用
张虎宁,张文月,温升鹏,畅思容,郭怡,宝瑞,孙岳,杨安宁,刘志宏..基于网络药理学、分子对接与实验验证探讨熊果酸治疗矽肺纤维化的作用机制[J].中国比较医学杂志,2025,35(12):1-12,12.基金项目
国家自然科学基金(82260142,82360639) （82260142,82360639）
宁夏自然科学基金(2022AAC03128,2024AAC0323) （2022AAC03128,2024AAC0323）
中科院西部青年学者项目(2024AAC0323) （2024AAC0323）
宁夏回族自治区青年拔尖人才培养项目(2022AAC05025). （2022AAC05025）
