基于网络药理学和分子对接探究健脾渗湿方治疗高尿酸血症的作用机制

Exploring the Mechanism of Jianpi Shenshi Formula for the Treatment of Hyperuricemia Based on Network Pharmacology and Molecular Docking

目的运用网络药理学方法和和分子对接技术探讨健脾渗湿方(Jianpi Shenshi Formula)治疗高尿酸血症(hyperuricemia,HUA)的潜在作用机制。方法通过TCMSP、BATMAN以及TCM-ID结合文献检索,筛选健脾渗湿方的活性成分,再通过SwissTargetPrediction获取成分对应的靶点。使用Cytoscape 3.8.0软件构建“药物-成分”网络,分析获取健脾渗湿方的主要活性成分。通过GeneCards、OMIM以及disgenet数据库获取高尿酸血症的相关靶点。将健脾渗湿方和高尿酸血症的交集靶点导入STRING数据库中进行蛋白互作(protein-protein interactions,PPI)网络分析,通过CytoHubba插件筛选网络hub靶点;同时使用R4.2.2软件对交集靶点进行GO功能及KEGG通路富集分析。运用CB-DOCK 2对hub靶点和主要成分进行分子对接。结果共筛选得到健脾渗湿方90个活性成分,其中槲皮素、山柰酚、木犀草素、豆甾醇、亚油酸乙酯等是主要活性成分,成分对应的837个靶点中有64个靶点与疾病相关靶点相交,其中CASP3、IL1B、IL6、PPARG、SIRT1、MAPK3、TNF、STAT3、TGFβ1、PTGS2、XDH等是hub靶点。潜在作用靶点主要富集在炎症、代谢、环境、细胞过程、生物系统及疾病等相关信号通路。结论健脾渗湿方可能通过槲皮素、山柰酚、木犀草素、豆甾醇、亚油酸乙酯等多种活性成分,对高尿酸血症相关的疾病信号通路(包括肿瘤、感染性疾病、代谢性疾病、心血管疾病等)以及代谢、免疫、炎症等生物学通路进行调节,发挥抑制尿酸生成和/或增加尿酸排泄、抗炎以及改善相关并发症的作用。

Objective To investigate the potential mechanism of Jianpi Shenshi Formula for the treatment of hyperuricemia(HUA)by using network pharmacology and molecular docking techniques.Methods The active ingredients of Jianpi Shenshi Formula were searched and screened by combining TCMSP,BATMAN,and TCM-ID database with literature,and then SwissTargetPrediction was used to obtain the corresponding targets of the ingredients.Cytoscape 3.8.0 was used to construct a"drug-ingredients"network to analyze and obtain the main active ingredients of Jianpi Shenshi Formula.The GeneCards,OMIM,and disgenet databases were used to obtain the relevant targets of hyperuricemia.The intersection targets of Jianpi Shenshi Formula and hyperuricemia were imported into the STRING database for protein-protein interaction PPI network analysis and hub targets for network were screened by CytoHubba plug-in.Meanwhile,the GO function and KEGG pathway enrichment analysis of the intersection targets were carried out using R4.2.2 software.Molecular docking of hub targets and key ingredients was performed using CB-DOCK 2.Results A total of 90 active ingredients of Jianpi Shenshi Formula were screened,among which quercetin,kaempferol,luteolin,stigmasterol,and ethyl linoleate were the main active ingredients,and 837 targets corresponding to the ingredients were obtained,with a total of 64 intersecting targets.CASP3,IL1B,IL6,PPARG,SIRT1,MAPK3,TNF,STAT3,TGFβ1,PTGS2,and XDH were the hub targets.The potential targets of action are mainly enriched in signaling pathways such as inflammation,metabolism,environment,cellular processes,biological systems,and hyperuricemia-related pathways.Conclusion Jianpi Shenshi Formula may exert effects on inhibition of uric acid production,and/or enhancement of uric acid excretion,anti-inflammation,and amelioration of related complications through the modulation of hyperuricemia-related signaling pathways(including neoplastic,infectious,metabolic,and cardiovascular diseases),as well as metabolic,immune,inflammatory,and other biological pathways by a variety of active ingredients such as quercetin,kaempferol,luteolin,stigmasterol,and ethyl linoleate.