{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:12:47Z","timestamp":1785283967995,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The quercetin-luteolin combination treatment group significantly ameliorated colon shortening, with colon length restored to 7.33\u202f\u00b1\u202f0.09\u202fcm (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05), 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-\u03baB signaling pathway, oxidative stress indicators were reduced by 52.6 and 20.2% (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05)., and the mRNA expression levels of inflammatory factors such as IL-1\u03b2, MyD88, P65, TNF-\u03b1, and TLR2 were downregulated. The expression level of AKT mRNA decreased by 69.5% (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05). In the LU\u202f+\u202fQR 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Ultimately, a synergistic alleviation model characterized by \u201cinhibition of inflammatory pathways\u2014restoration of barrier function\u2014regulation of microbial homeostasis\u201d was established. This study provides a theoretical foundation for the application of quercetin and luteolin in the treatment of colitis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1698231","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T15:45:32Z","timestamp":1760715932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Study on the role of the combination of quercetin and lutein in alleviating ulcerative colitis in mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhiyue","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bimal","family":"Chitrakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renli","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"112486","DOI":"10.1016\/j.intimp.2024.112486","article-title":"A comprehensive immunobiology review of IBD: with a specific glance to Th22 lymphocytes development, biology, function, and role in IBD","volume":"137","author":"Lv","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/s2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"5","author":"Alatab","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2428","DOI":"10.1016\/j.fshw.2023.03.010","article-title":"Effect of sodium alginate-based hydrogel loaded with lutein on gut microbiota and inflammatory response in DSS-induced colitis mice","volume":"12","author":"Xu","year":"2023","journal-title":"Food Sci Human Wellness"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1016\/s0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMra1102942","article-title":"Ulcerative colitis","volume":"365","author":"Danese","year":"2011","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5900","DOI":"10.3390\/molecules29245900","article-title":"Quercetin ameliorates acute lethal sepsis in mice by inhibiting caspase-11 noncanonical inflammasome in macrophages","volume":"29","author":"Kim","year":"2024","journal-title":"Molecules"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"8334","DOI":"10.1021\/acsomega.0c00804","article-title":"Quercetin alleviates intestinal oxidative damage induced by H2O2 via modulation of GSH: in vitro screening and in vivo evaluation in a colitis model of mice","volume":"5","author":"Dong","year":"2020","journal-title":"ACS Omega"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"30","DOI":"10.4274\/balkanmedj.galenos.2023.2023-10-9","article-title":"Quercetin attenuates endoplasmic reticulum stress and apoptosis in TNBS-induced colitis by inhibiting the glucose regulatory protein 78 activation","volume":"41","author":"Top\u00e7u-Tarlada\u00e7al\u0131\u015f\u0131r","year":"2024","journal-title":"Balk Med J"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3390\/pathogens8030126","article-title":"Alteration of gut microbiota in inflammatory bowel disease (IBD): cause or consequence? 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