Neohesperidin Attenuates\nDSS-Induced Ulcerative Colitis\nby Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and\nModulating Intestinal Flora Composition

Flavonoid natural products are emerging as a promising\napproach\nfor treating Ulcerative Colitis (UC) due to their natural origin and\nminimal toxicity. This study investigates the effects of Neohesperidin\n(NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced\nUC in mice, focusing on the underlying molecular mechanisms. Early\nintervention with NEO (25 and 50 mg/kg) mitigated colon shortening,\nrestored damaged barrier proteins, and significantly reduced the inflammatory\ncytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling\npathway and enhanced the levels of intestinal barrier proteins (Claudin-3\nand ZO-1). Additionally, NEO increased beneficial intestinal probiotics\n(<i>S24–7</i> and <i>Lactobacillaceae</i>) while reducing harmful bacteria (<i>Erysipelotrichi</i>, <i>Enterobacteriaceae</i>). Fecal microbial transplantation\n(FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC\nsymptoms. In conclusion, early NEO intervention may alleviate DSS-induced\nUC by inhibiting inflammatory responses, preserving intestinal barrier\nintegrity and modulating gut microbiota.