Ginseng-derived extracellular vesicles alleviate ulcerative colitis by regulating macrophage glycolytic reprogramming and H3K18la-mediated epigenetic modification.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options due to adverse effects and variable response rates. Plant-derived extracellular vesicles have emerged as promising therapeutic agents owing to their biocompatibility. Although Methods: GEs were isolated and characterized. The therapeutic effects of GEs were evaluated in DSS-induced UC mice. Single-cell RNA sequencing was performed to profile colonic immune cells. In vitro experiments using RAW264.7 macrophages and Caco-2 intestinal epithelial cells were conducted to investigate macrophage polarization, glycolytic metabolism, histone lactylation, and barrier function. Gut microbiota and short-chain fatty acid (SCFA) profiles were analyzed by 16S rRNA sequencing and gas chromatography. Results: GEs alleviated DSS-induced colitis symptoms, reduced pro-inflammatory cytokines, restored tight junction proteins, and exhibited good biosafety. Single-cell sequencing revealed that GEs remodeled colonic macrophage subsets, reducing pro-inflammatory Ccl7 Conclusion: This study demonstrates that GEs alleviate UC by inhibiting macrophage glycolysis, reducing H3K18la-mediated pro-inflammatory gene expression, protecting the intestinal barrier, and modulating the gut microbiota. These results offer new experimental support for GE-based UC therapy and establish a basis for mechanistic and translational follow-up studies.