Background: Gout is a common disease with high incidence due to unhealthy diet and living habits. Si Miao Wan, 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.
Methods: Based on network pharmacology, Si Miao Wan 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 Si Miao Wan 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.
Results: 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 Si Miao Wan 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 Si Miao Wan can decreased serum UA and XOD levels in hyperuricemic-gout mice, and improved renal function. Furthermore, Si Miao Wan certainly regulates the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA in ankle tissue in hyperuricemic-gout mice.
Conclusion: Collectively, this research predicted a multiple compounds, targets, and pathways model mechanism of Si Miao Wan in the prevention and treatment of gout, providing new ideas and methods for in-depth research, via vivo experiments.