Protective effects of Shabyar on endotoxin-induced uveitis in male rats: Involvement of the JAK2/STAT3 and VEGF pathways.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Anterior uveitis (AU) is the prevalent form of uveitis among ocular disease. Shabyar (SBY), as a traditional central asian ethnic medicine, has been used in the treatment of ocular diseases. However, its potential mechanism of action in treating AU remains unclear. AIM OF THE STUDY: This study aimed to investigate the therapeutic effect and related mechanisms of SBY on endotoxin-induced uveitis (EIU) in male rats. MATERIALS AND METHODS: Network pharmacology (NP) was applied to identify the potential pharmacological target network of SBY in treating EIU. Commercial assay kits were used to measure the levels of inflammatory markers and vascular regulators. The leakage of Evans blue (EB) in retina was quantitatively assessed. Immunohistochemistry was performed to evaluate the relative expression of JAK2, p-JAK2, STAT3, and p-STAT3 in retinal tissues. Western blotting was conducted in lipopolysaccharide (LPS)-stimulated RAW264.7 cells to investigate the effects of SBY on the JAK2/STAT3 pathway. RESULTS: SBY alleviated inflammation in EIU male rats by reducing inflammatory cell infiltration and cytokine release, an effect potentially related to suppression of JAK2/STAT3 pathway activation. Correspondingly, in LPS-induced RAW264.7 cells, SBY's anti-inflammatory action involved regulation of the JAK2/STAT3 pathway. Moreover, SBY inhibited the level of VEGF, upregulated PEDF expression, and thereby alleviated blood-retinal barrier (BRB) leakage and retinal edema in EIU male rats. CONCLUSION: The protective effects of SBY on EIU in male rats may be mediated through the involvement of the JAK2/STAT3 and VEGF pathways. However, it should be noted that the absence of a direct comparison with a standard clinical corticosteroid (e.g., dexamethasone) in the in vivo study limits to some extent the immediate clinical potency benchmarking of SBY.