Neohesperidin Attenuates DSS-Induced Ulcerative Colitis by Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and Modulating Intestinal Flora Composition
Tianyuan Ju, Zheyu Song, Di Qin, Ji Cheng, Tong Li, Guiqiu Hu, Shoupeng Fu
Abstract
Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics ( S24–7 and Lactobacillaceae ) while reducing harmful bacteria ( Erysipelotrichi, Enterobacteriaceae ). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.