Extracellular Vesicles Derived from Elaeocarpus braceanus Alleviate DSS-Induced Ulcerative Colitis in Mice Through Multiple Pathways

Aim of the study: This study aims to isolate extracellular vesicles derived from Elaeocarpus braceanus fruits (EBDEVs) and evaluate their alleviating efficacy as nature nanoparticles against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Methods: EBDEVs were isolated by differential and density gradient ultracentrifugation, then characterized for morphology, size, stability, and composition. Their anti-inflammatory activity was assessed in LPS-stimulated RAW264.7 macrophages. In vivo, acute UC was induced in C57BL/6 mice by 2.5% DSS. Disease severity, intestinal barrier integrity, TLR4/MyD88/NF-κB pathway activation, and gut microbiota composition were evaluated. Results: EBDEVs exhibited a typical spherical structure and were rich in bioactive components such as lipids, flavonoids, and terpenoids. Macrophages readily internalized them and significantly inhibited LPS-induced NO production. In UC mice, EBDEVs ameliorated weight loss, colon shortening, and tissue damage, while reducing serum inflammatory cytokines. EBDEVs restored intestinal barrier function by regulating tight junction proteins. Mechanistically, EBDEVs suppressed the activation of TLR4/MyD88/NF-κB and downstream NLRP3 inflammasome inflammatory signaling cascades, and remodeled the dysregulated gut microbiota structure. Conclusions: EBDEVs alleviate DSS-induced UC in mice by repairing the intestinal barrier, inhibiting inflammatory pathways, and modulating gut microbiota.