By integrating network pharmacology and animal experiments, we studied the pharmacodynamic mechanism of the Tibetan medicine Liurui Capsules in the treatment of experimental autoimmune uveitis(EAU). The active ingredients and targets of Liurui Capsules were searched against the Encyclopedia of Traditional Chinese Medicine(ETCM), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM), and relevant literatures. The EAU-related targets were obtained from Gene Expression Omnibus(GEO), GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). The common targets shared by Liurui Capsules and EAU were identified, and the protein-protein interaction(PPI) network was established via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were conducted via g: Profiler. The rat model of EAU was induced by interphotoreceptor retinoid-binding protein(IRBP) and treated with Liurui Capsules. The inflammatory response of anterior segment and the pathological morphology of retina were observed. The mRNA and protein levels of delta-like ligand 4(DLL4), Notch1, interleukin-17(IL-17), and tumor necrosis factor-alpha(TNF-α) were determined by real-time quantitative PCR(q-PCR) and Western blot, respectively. The network pharmacology analysis predicted 51 common targets of Liurui Capsules and EAU, which were mainly involved in IL-17, TNF, and nuclear factor-kappa B(NF-κB) signaling pathways, as well as liposome receptors and other biological processes. Compared with the control group, the modeling of EAU caused inflammatory changes in the anterior segment and retina and up-regulated mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α in ocular tissue. Compared with the model group, Liurui Capsules reduced the inflammatory reaction of anterior segment and retina and down-regulated the mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α. Liurui Capsules can down-regulate the expression of the proteins involved in DLL4/Notch1/IL-17 signaling pathway in ocular tissue and alleviate the ocular inflammation, which may be one of the mechanisms of Liurui Capsules in the treatment of EAU.
Keywords: Liurui Capsules; experimental autoimmune uveitis; network pharmacology; pharmacodynamic mechanism.