College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
BMC Complement Med Ther. 2022 Jun 7;22(1):152. doi: 10.1186/s12906-022-03622-0.
Gout is a common disease with high incidence due to unhealthy diet and living habits. Simiao Powder, as a classic formula consisted of four common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism of Simiao Powder is still unclear.
Based on network pharmacology, Simiao Powder active compounds were identified in TCMSP, ETCM and BATMAN database, used to establish a network of interaction between potential targets of Simiao Powder and known therapeutic targets of gout. Subsequently, the key potential targets are being used for protein-protein interaction, GO enrichment analysis and KEGG pathway enrichment analysis through several authoritative open databases. Molecular docking through AutoDockTools software can verify interaction between molecules. Finally, to validate the predicted results, in vivo experiments based on hyperuricemic-gout mice model were designed and treated with Simiao powder and allopurinol. Serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) and xanthine oxidase (XOD) were determined using a customized assay kit while the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA were analyzed through qRT-PCR.
Disease-target-compound network was visualized basing on the 20 bioactive compounds and the 19 potential targets using Cytoscape software. The results of PPI analysis, GO enrichment and KEGG pathway enrichment analysis indicate that the potential mechanism of Simiao Powder in treating gout may be achieved by regulating immune and inflammatory reactions, improving metabolism and endocrine. The results of molecular docking show that most of the targets and components have good binding activity. In vivo experiments revealed that Simiao powder can decreased serum UA and XOD levels in hyperuricemic-gout mice, and improved renal function. Furthermore, Simiao powder certainly regulates the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA in ankle tissue in hyperuricemic-gout mice.
Collectively, this research predicted a multiple compounds, targets, and pathways model mechanism of Simiao Powder in the prevention and treatment of gout, providing new ideas and methods for in-depth research, via vivo experiments.
痛风是一种常见疾病,由于饮食和生活习惯不健康,其发病率很高。四妙散作为一种由四种常见草药组成的经典方剂,自古以来就广泛应用于临床实践,用于预防和治疗痛风。然而,四妙散的药理机制尚不清楚。
基于网络药理学,在 TCMSP、ETCM 和 BATMAN 数据库中鉴定四妙散的活性化合物,建立四妙散潜在靶点与已知痛风治疗靶点的相互作用网络。随后,利用几个权威的开放数据库对关键潜在靶点进行蛋白质-蛋白质相互作用、GO 富集分析和 KEGG 通路富集分析。通过 AutoDockTools 软件进行分子对接可以验证分子间的相互作用。最后,设计基于高尿酸血症-痛风小鼠模型的体内实验,用四妙散和别嘌醇进行治疗,验证预测结果。采用定制试剂盒测定血清尿酸(UA)、肌酐(Cr)、血尿素氮(BUN)和黄嘌呤氧化酶(XOD)水平,通过 qRT-PCR 分析 PPAR-γ、PTGS1、IL-6 和 Bcl2 mRNA 的表达。
利用 Cytoscape 软件可视化基于 20 种生物活性化合物和 19 个潜在靶点的疾病-靶-化合物网络。PPI 分析、GO 富集和 KEGG 通路富集分析的结果表明,四妙散治疗痛风的潜在机制可能是通过调节免疫和炎症反应、改善代谢和内分泌来实现的。分子对接的结果表明,大多数靶点和成分具有良好的结合活性。体内实验表明,四妙散可降低高尿酸血症-痛风小鼠血清 UA 和 XOD 水平,改善肾功能。此外,四妙散肯定调节高尿酸血症-痛风小鼠踝关节组织中 PPAR-γ、PTGS1、IL-6 和 Bcl2 mRNA 的表达。
综上所述,本研究通过体内实验预测了四妙散预防和治疗痛风的多化合物、靶点和通路模型机制,为深入研究提供了新的思路和方法。