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Luteolin Modulate Endoplasmic Reticulum Stress by Targeting SIRT1 to Ameliorate DSS‐Induced Ulcerative Colitis in Mice

Haixiang Guo,Zhong-Hao Ji,Bingbing Wang,Yu Xiao,Jinping Hu,Yi Zheng,Wei Gao,Bao Yuan

Published 2025 in The FASEB Journal

ABSTRACT

Ulcerative colitis (UC) is a recurrent, chronic disease whose main symptoms include weight loss, diarrhea, and blood in the stool. In recent years, the incidence of UC has been increasing year by year, which seriously affects the daily life of patients. 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)‐induced 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 vitro. It was found that Lut treatment inhibited TM/TG‐induced ER stress and apoptosis. However, these inhibitory effects of Lut were attenuated by SIRT1 silencing in TM‐treated 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‐related diseases in humans.

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