Endarachne binghamiae Extract Alleviates Colitis by Suppressing NLRP3 Inflammasome Activation via Regulation of NOX-iNOS Crosstalk.

Inflammatory bowel disease (IBD) is triggered by genetic predisposition and chronic inflammation, with aberrant activation of the innate immune complex NLRP3 inflammasome playing a pivotal role in its pathogenesis. In this study, we investigated the effects of a hot water extract from the brown alga Endarachne binghamiae (EB-WE) on the inhibition of NLRP3 inflammasome activation, with a focus on its antioxidant properties, in various inflammation models. In bone marrow-derived macrophages (BMDMs), NLRP3 inflammasome activation was induced using LPS and ATP, and EB-WE pretreatment (100, 200 µg/mL) significantly reduced the secretion of IL-1β and IL-18. Confocal immunofluorescence analysis further confirmed that EB-WE suppressed the formation of the NLRP3-ASC/caspase-1 complex. Furthermore, the in vivo anti-IBD efficacy of EB-WE was assessed using a DSS-induced mouse model, in which colonic inflammation and NLRP3-mediated responses were prominent. Oral administration of EB-WE (2 or 5 mg/day) markedly ameliorated clinical symptoms, such as weight loss, diarrhea, and rectal bleeding, and significantly reduced the disease activity index (DAI). EB-WE also decreased serum pro-inflammatory cytokine levels and the expression of NLRP3 inflammasome-related molecules in colon tissue at both the gene and protein levels. In both BMDMs and the IBD mouse model, we further analyzed the upstream regulatory pathway involving NOX2-iNOS. EB-WE efficiently inhibited the activation of the NOX-iNOS axis and NF-κB phosphorylation, thereby alleviating inflammasome activation associated with DSS-induced oxidative stress and neutrophil/macrophage infiltration. Collectively, these results demonstrate that EB-WE effectively suppresses the formation and activation of the NLRP3 inflammasome by modulating the NOX-iNOS axis and the NF-κB pathway via antioxidant mechanisms. These findings suggest that EB-WE holds promise as a novel marine-derived natural therapeutic agent for the treatment of chronic inflammatory diseases.