Attenuation by Zhiqiao neohesperidin on dextran sulfate sodium-induced colitis in mice through inhibition of the TLR4/NF-κB pathway

Ulcerative colitis is a chronic inflammatory disease closely associated with immune dysregulation. Zhiqiao (Fructus aurantii), the nearly mature fruit of Citrus aurantium L., is widely used in traditional dietary therapy for intestinal health. Here, we extracted and purified neohesperidin from Zhiqiao and explored its alleviative effects on dextran sulfate sodium-induced colitis and related inflammatory pathways in mice. The results showed that neohesperidin administration significantly ameliorated symptoms of colitis and reduced the accumulation of inflammatory cytokines in mouse tissues and serum. Decreases in the TLR4, MyD88, and NF-kappa B p65 mRNA expression levels indicated that activity of the TLR4/NF-kappa B signaling pathway was downregulated. Molecular docking results showed that neohesperidin occupies the lipopolysaccharide-binding pocket of MD-2 and binds to the interacting surface of TLR4/MD-2 and that of the subsequently formed homodimer, thereby disrupting recognition of inflammatory ligands by the TLR4-mediated pathway. Neohesperidin holds promise for the adjunctive treatment of ulcerative colitis.