{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE302nnn/GSE302567/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302567"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nicotine and quercetin alleviate ulcerative colitis through inhibition of PI3K/AKT and NF-κB pathways","description":"Ulcerative colitis (UC) remains a therapeutic challenge due to its chronicity, adverse effects of current drugs, and high relapse rates. Smoking inversely correlates with UC risk. Nicotine (NIC) shows UC efficacy but causes non-smoker intolerance. Bioinformatic identification of tobacco-derived quercetin (QUE), an α7 nAChR enhancer, suggests its potential as a NIC synergist for reduced side effects. We thus hypothesized that half-dose NIC-QUE co-therapy would exert superior anti-colitis effects. Using a DSS-induced murine colitis model, we performed a multidimensional assessment spanning: Clinical phenotypes (body weight, disease activity index (DAI), colon length, histopathology), Gut microenvironment (gut microbiota composition, short-chain fatty acids (SCFAs) and barrier integrity) and Inflammatory mechanisms (inflammatory cytokines and signaling 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","dates":{"publication":"2026/07/12"},"accession":"GSE302567","cross_references":{"GSM":["GSM9106262","GSM9106251","GSM9106272","GSM9106261","GSM9106271","GSM9106260","GSM9106270","GSM9106259","GSM9106269","GSM9106258","GSM9106257","GSM9106268","GSM9106256","GSM9106267","GSM9106266","GSM9106255","GSM9106265","GSM9106254","GSM9106253","GSM9106264","GSM9106252","GSM9106263"],"GPL":["36028"],"GSE":["302567"],"taxon":["Musculus"]}}