基于网络药理学和分子对接探讨二氢杨梅素对线粒体自噬的作用机制

Mechanism of Dihydromyricetin on Mitophagy by Network Pharmacology and Molecular Docking

目的利用网络药理学和分子对接方法探讨二氢杨梅素对线粒体自噬的作用机制。方法使用Swiss Target Prediction数据库预测二氢杨梅素的相关靶点;通过GeneCards数据库和NCBI数据库收集线粒体自噬的相关靶点;利用String数据库构建PPI网络,通过R 4.1.3软件进行GO功能和KEGG通路富集分析,使用Cytoscape 3.7.2软件构建“化合物-靶点-信号通路”网络图;运用PyMOL 2.4.0软件和Auto Dock Tools 1.5.6、Autodock Vina软件进行分子对接。结果最终得到二氢杨梅素的作用靶点70个,二氢杨梅素与线粒体自噬共有靶点15个;二氢杨梅素与线粒体自噬主要涉及916个生物过程包括对氧化应激、金属离子的反应等,主要富集的信号通路包括癌症蛋白聚糖、癌症、MAPK等40条;“化合物-靶点-通路”网络图显示,二氢杨梅素与线粒体自噬与多个靶点、多个通路具有相互作用;分子对接中二氢杨梅素均能同15个靶点进行有效的结合,其中与FGFR1结合效果最佳,与PPARG的结合效果次之。结论二氢杨梅素可通过HIF1A、KDR、APP等多个靶点调控癌症蛋白聚糖、癌症、MAPK等多个信号通路参与线粒体自噬。

Objective To explore the mechanism of dihydromyricetin on mitophagy using network pharmacology and molecular docking methods.Methods The related targets of dihydromyricetin were predicted using the Swiss Target Prediction database;the related targets of mitophagy were collected from the GeneCards database and the NCBI database;the PPI network was constructed using the String database,and the GO function and KEGG pathway were performed by R 4.1.3 software.Cytoscape 3.7.2 software was used to construct"compound-target-pathway"network diagram;PyMOL 2.4.0 software,Auto Dock Tools 1.5.6 software and Autodock Vina software were used for molecular docking.Results Finally,70 targets of dihydromyricetin were obtained,and 15 common targets of dihydromyricetin and mitophagy were obtained.Dihydromyricetin and mitophagy were mainly involved in 916 biological processes,including responses to oxidative stress and metal ions,and the main enriched signaling pathways include 40 pathways such as cancer proteoglycan,cancer,and MAPK;"compound-target-pathway"network diagram showed that dihydromyricetin and mitophagy interacted with multiple targets and multiple pathways.In molecular docking,dihydromyricetin could effectively bind to 15 targets,among which the binding effect with FGFR1 was the best,followed by the binding effect with PPARG.Conclusion Dihydromyricetin can participate in mitophagy by regulating cancer proteoglycan,cancer,MAPK and other signaling pathways through multiple targets such as HIF1A,KDR,and APP.