Sinomenine alleviates experimental autoimmune uveitis in rats: Possible involvement of PI3K/AKT and NF-κB signaling pathways

Abstract

Uveitis is an inflammatory ocular condition characterized by an autoimmune etiology. Sinomenine (SIN), the main active constituent of the rhizome of Sinomenium acutum (Thunb.) Rehd. et Wils., exhibits both anti-inflammatory and immunosuppressive properties. The present study sought to investigate the therapeutic effects of SIN on experimental autoimmune uveitis (EAU) in rats and to elucidate its underlying mechanisms. A bioinformatics analysis was conducted to identify signaling pathways implicated in the pathogenesis of uveitis, leading to the identification of the PI3K/AKT and NF-κB pathways for further experimental validation. An EAU model was subsequently established, and the ocular surface morphology was examined using slit lamp microscopy and hematoxylin-eosin staining. Immunofluorescence was utilized to measure the protein expression and distribution. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. Experimental findings demonstrated that SIN significantly decreased ocular inflammation scores. Further validation revealed that SIN significantly elevated levels of interleukin-10 (IL-10) while reducing levels of IL-17, tumor necrosis factor-α (TNF-α), and IL-1β in EAU rats. SIN significantly suppressed the expression of phosphorylated proteins in the PI3K/AKT and NF-κB pathways. In addition, it reduced the expression of RORγt while enhancing the expression of Foxp3, the transcription factors associated with Th17 cells and Tregs, respectively. In summary, our data demonstrate that SIN alleviates EAU inflammation by inhibiting the activation of the PI3K/AKT and NF-κB signaling pathways and restoring the balance between Th17 and Tregs. These findings highlight SIN as a promising therapeutic agent for the treatment of uveitis.