Combined treatment shows improved ulcerative colitis outcomes by enhancing gut microbiota and inflammatory regulation.
Introduction This study aims to investigate the ameliorative effects and molecular mechanisms of combined quercetin and luteolin intervention on dextran sulfate sodium (DSS)-induced colitis in mice. Methods By establishing a DSS-induced colitis model, we systematically evaluated the comprehensive effects of the combined treatment on colonic histopathological damage, inflammatory cytokine expression, intestinal barrier function, and gut microbiota composition. Results The quercetin-luteolin combination treatment group significantly ameliorated colon shortening, with colon length restored to 7.33 ± 0.09 cm ( p < 0.05), reduced the severity of colonic ulcers, and decreased the disease activity index. The protective effects were manifested in two aspects: first, by synergistically upregulating the expression of tight junction proteins ZO-1, claudin-1, and occludin, the combined treatment maintained the functional integrity of the intestinal epithelial barrier; second, by inhibiting the PI3K/AKT/NF-κB signaling pathway, oxidative stress indicators were reduced by 52.6 and 20.2% ( p < 0.05)., and the mRNA expression levels of inflammatory factors such as IL-1β, MyD88, P65, TNF-α, and TLR2 were downregulated. The expression level of AKT mRNA decreased by 69.5% ( p < 0.05). In the LU + QR group compared to the IBD group. Additionally, the combined treatment reshaped the gut microbiota of colitis mice by modulating the relative abundances of Firmicutes, Bacteroidota, and Pseudomonadota. Discussion Ultimately, a synergistic alleviation model characterized by “inhibition of inflammatory pathways—restoration of barrier function—regulation of microbial homeostasis” was established. This study provides a theoretical foundation for the application of quercetin and luteolin in the treatment of colitis.
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