Nicotine and quercetin alleviate ulcerative colitis through inhibition of PI3K/AKT and NF-κB pathways

The half-dose NIC-QUE combination almost outperformed monotherapies across all dimensions, such as body weight, DAI, colon length, histopathology. Mechanistically, synergy arose from: the synergistic effect involved: reshaping gut microbiota structure (notably increasing Clostridia and Eubacterium while reducing Erysipelotrichia), restoring key SCFA levels (acetate, butyrate, propionate, valerate), enhancing intestinal barrier integrity (ZO-1, Muc2), and critically, suppressing the activation of the PI3K/AKT and NF-κB signaling pathways.

To our knowledge, this is the first study demonstrating that half-dose NIC-QUE co-administration constitutes a novel UC therapeutic strategy. Its core mechanism involves coordinated restoration of the gut microbiome-metabolite barrier and suppression of the PI3K/AKT/NF-κB inflammatory cascade