基于网络药理学及分子对接预测木犀草素治疗痛风作用的研究

Mechanism of luteolin in the treatment of gout based on network pharmacology and molecular docking

目的通过网络药理学和分子对接技术探讨木犀草素治疗痛风的作用机制。方法采用Swiss Target Prediction数据库搜集木犀草素作用靶点,TTD数据库、Drugbank数据库、DisGeNET数据库搜集痛风疾病靶点并结合文献进行整理筛选;对两者靶点取交集后采用String数据库构建木犀草素治疗痛风潜在靶点的蛋白质相互作用网络图(PPI);利用Cytoscape软件进行核心靶点筛选;随后对潜在靶点进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。最后,基于AutoDock4.2.6软件对木犀草素小分子与核心靶点使用分子对接技术进行对接验证。结果共筛选出19个共同潜在靶点。其中,核心靶点是PTGS2、ABCG2、ABCB1、SRC、AKR1C3等。这些靶点主要通过花生四烯酸代谢过程、ABC转运通路等发挥防治痛风的作用。结论木犀草素可能通过抑制PTGS2基因表达COX-2控制痛风急性发作,并可能通过ABCG2促进尿酸排泄发挥降血尿酸的作用。

Objective To investigate the mechanism of luteolin in treatment of gout by using the network pharmacology and molecular docking.Methods The therapeutic targets of luteolin were selected by Swiss Target Prediction,and the targets of gout were screened from Therapeutic Target Database(TTD),Drugbank,and DisGeNET and then arranged with the combination of literature.After taking the overlapping sets of the two targets,the protein-protein interaction(PPI)network graph of the potential targets in treatment of gout with luteolin was constructed by using String database.Then core targets were screened by Cytoscape.The functional enrichment analysis of Gene Ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Gene and Genome(KEGG)were performed on the potential targets.At last,docking verification was performed on small molecules of luteolin and core targets by using molecular docking technology based on AutoDock4.2.6 software.Results A total of 19 overlapping potential targets were screened,among which the core targets were PTGS2,ABCG2,ABCB1,SRC and AKR1C3,etc.,and these overlapping targets played a role in the prevention and treatment of gout mainly through arachidonic acid metabolic process and ABC transport pathway.Conclusion Luteolin may control acute gout attack by inhibiting PTGS2 gene expression COX-2,and may reduce uric acid by promoting uric acid excretion through ABCG2.