基于网络药理学和分子对接探究山楂治疗高脂血症的作用机制

Mechanism of hawthorn in treating hyperlipidemia based on network pharmacology and molecular docking

目的 运用网络药理学和分子对接技术探究山楂治疗高脂血症的作用机制。方法 通过HERB、ETCM、SymMap、BATMAN-TCM、PubChem、SwissTargetPretiction和UniProt数据库以及文献补充获得山楂的有效成分及其对应的靶点。通过GeneCards、OMIM和DAVID数据库收集高脂血症的相关靶点并对交集靶点进行GO和KEGG富集分析。再利用Open Babel GUI、AutoDockTools-1.5.7软件对主要成分与靶点进行分子对接。最后通过BioGPS数据库收集高脂血症的组织分布信息,数据处理后利用Cytoscape 3.9.1软件将结果可视化。结果 通过网络药理学分析,获得69个山楂的有效成分,其中35个活性成分与山楂治疗高脂血症相关。成分-疾病靶基因中的188个交集基因在心脏、肝脏、肺、全血、骨骼肌、前列腺和甲状腺中表达情况良好。关键靶点有12个,包括丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤坏死因子(TNF)和白细胞介素(IL-6)等。KEGG富集分析得到201条通路,包括脂质和动脉粥样硬化通路、流体剪切应力与动脉粥样硬化通路和PI3K-Akt通路等。分子对接结果显示山楂的主要成分与关键靶点具有良好的结合能力。结论 网络药理学研究表明,山楂治疗高脂血症是通过多成分-多靶点-多通路共同实现的,为后期山楂治疗高脂血症的研究提供参考。

Objective To explore the mechanism of hawthorn in treating hyperlipidemia by network pharmacology and molecular docking technology.Methods The effective components of hawthorn and their corresponding targets were obtained by HERB,ETCM,SymMap,BATMAN-TCM,PubChem,SwissTargetPretiction,UniProt database and literature supplement.The related targets of hyperlipidemia were collected by GeneCards,OMIM and DAVID databases,and GO and KEGG enrichment analysis were performed on the intersection targets.The main components and targets were molecularly docked using Open Babel GUI and AutoDockTools-1.5.7 software.Finally,the tissue distribution information of hyperlipidemia was collected through the BioGPS database,and the results were visualized by Cytoscape 3.9.1 software after data processing.Results Through network pharmacology analysis,69 active ingredients of hawthorn were obtained,of which 35 active ingredients were related to hawthorn in the treatment of hyperlipidemia.The 188 intersection genes of component-disease target genes were well expressed in heart,liver,lung,whole blood,skeletal muscle,prostate and thyroid.There are 12 key targets,including serine/threonine protein kinase(AKT1),tumor necrosis factor(TNF)and interleukin(IL-6).KEGG enrichment analysis obtained 201 pathways,including lipid and atherosclerosis,fluid shear stress and atherosclerosis,and PI3K-Akt pathway.Molecular docking results showed that the main components of hawthorn had good binding ability with key targets.Conclusion Network pharmacology studies have shown that hawthorn treatment of hyperlipidemia is achieved through multi-component-multi-target-multi-pathway,providing a reference for the later study of hawthorn treatment of hyperlipidemia.