Guo Hai-Xiang, Ji Zhong-Hao, Wang Bing-Bing, Xiao Yu, Hu Jin-Ping, Zheng Yi, Gao Wei, Yuan Bao
Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, China.
Department of Basic Medicine, Changzhi Medical College, Changzhi, Shanxi, China.
FASEB J. 2025 Apr 15;39(7):e70529. doi: 10.1096/fj.202403418R.
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.
溃疡性结肠炎（UC）是一种复发性的慢性疾病，其主要症状包括体重减轻、腹泻和便血。近年来，UC的发病率逐年上升，严重影响患者的日常生活。木犀草素（Lut）作为一种黄酮类化合物，广泛存在于各种蔬菜和水果中，并已显示出具有多种药理活性。这项研究调查了Lut对葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎（UC）的影响，特别关注内质网（ER）应激在其中的作用。结果表明，在用木犀草素治疗的UC模型小鼠中，包括疾病表型、炎症因子水平升高、肠道屏障损伤和肠道微生物群破坏在内的结肠炎症状得到了显著缓解。此外，Lut减轻了UC小鼠的内质网应激和细胞凋亡。然后，我们在体外研究了Lut对毒胡萝卜素（TG）和衣霉素（TM）诱导的HT29细胞内质网应激和细胞凋亡的影响。发现Lut处理可抑制TM/TG诱导的内质网应激和细胞凋亡。然而，在TM处理的HT29细胞中，SIRT1沉默减弱了Lut的这些抑制作用。总之，我们的结果表明，在结肠炎小鼠模型中补充Lut可改善小鼠的结肠炎症状，这为Lut在预防人类炎症相关疾病中的进一步应用提供了理论依据。
