Artesunate suppresses ocular inflammation in endotoxin-induced uveitis through inhibiting the NF-κB signaling pathway and M1 macrophage polarization.

Abstract

Uveitis is an inflammatory eye disease that can lead to visual impairment and blindness, highlighting the need for safer and more effective treatments. This study demonstrates the protective effects of artesunate (ART) and artesunate sustained-release formulation (ARTSR) against endotoxin-induced uveitis (EIU) in rat and rabbit models. In vitro, ART inhibited migration-related genes and reduced migratory ability in lipopolysaccharide (LPS)-stimulated RAW264.7 cells (a murine macrophage cell line). ART effectively suppressed LPS-induced inflammation in BV2 cells (a murine microglial cell line) by modulating microglial polarization and downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Notch1 signaling pathways. In EIU rats, ART attenuated clinical inflammation scores, prevented retinal thickening, and reduced inflammatory cell infiltration. ART downregulated pro-inflammatory mediators and M1-related genes, and upregulated M2-related genes in EIU rat eyes, primarily through suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. In EIU rabbits, ARTSR reduced protein concentration and cell infiltration in aqueous humor. These findings highlight the therapeutic potential of ART and ARTSR in uveitis by modulating inflammatory responses.