[关键词]
[摘要]
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。
[Key word]
[Abstract]
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.
[中图分类号]
R285.5
[基金项目]
云南省重大科技专项计划——云南省中医 (风湿病) 临床医学研究中心项目 (202102AA310006) ;国家中医药管理局高水平中医药重点 学科 (风湿痹病学) 建设项目 (zyyzdxk-2023189);云南省教育厅科学研究基金项目 (2023Y0463)。