Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology

Background: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics.Methods: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database.Results: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK.Conclusion: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation.