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Luteolin (Lut), as a flavonoid, is widely found in a variety of vegetables and fruits and has been shown to have a variety of pharmacological activities. This work investigated the effects of Lut on dextrose sodium sulfate (DSS)\u2010induced ulcerative colitis (UC) in mice, with a special focus on the role of endoplasmic reticulum (ER) stress in this. The outcomes demonstrated that colitis symptoms, including disease phenotype, elevated inflammatory factor levels, intestinal barrier damage, and gut microbiota disruption, were considerably alleviated in UC model mice treated with luteolin. Also, Lut alleviated ER stress and apoptosis in UC mice. We then explored the effects of Lut on ER stress and apoptosis induced by thapsigargin (TG) and tunicamycin (TM) in HT29 cells in\u00a0vitro. It was found that Lut treatment inhibited TM\/TG\u2010induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM\u2010treated HT29 cells. In conclusion, our results suggest that Lut supplementation in a mouse model of colitis improves the symptoms of colitis in mice, which provides a theoretical basis for further application of Lut in the prevention of inflammation\u2010related diseases in humans.<\/jats:p>","DOI":"10.1096\/fj.202403418r","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T03:21:06Z","timestamp":1744255266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Luteolin Modulate Endoplasmic Reticulum Stress by Targeting\n                    <scp>SIRT1<\/scp>\n                    to Ameliorate\n                    <scp>DSS<\/scp>\n                    \u2010Induced Ulcerative Colitis in Mice"],"prefix":"10.1096","volume":"39","author":[{"given":"Hai\u2010Xiang","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Animals, College of Animal Sciences Jilin University  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