Lv Weiguang, Han Shengnan, Li Ke, Yan Aimin, Wang Wei, Lu Wanping, Han Jing, Zhang Chenggang
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
Front Pharmacol. 2025 Jul 31;16:1564783. doi: 10.3389/fphar.2025.1564783. eCollection 2025.
Ulcerative colitis (UC) is a nonspecific inflammatory disease. Baicalein has potential value in treating UC, but its mechanism is unclear. This study aims to evaluate the protective effects of baicalein on dextran sodium sulfate (DSS)-induced UC mice. The UC model was established by 4% DSS solution for 7 days. Treatments included baicalein (10 mg/kg, 20 mg/kg) and sulfasalazine (200 mg/kg) via oral gavage. Colonic damage was assessed through body weight, disease activity index (DAI), histopathology (H&E staining) and colon length. Inflammatory cytokines were measured by ELISA, while oxidative stress markers and iron content were analyzed by colorimetric assays. Protein expression was evaluated by Western blot, and gene levels by RT-qPCR. Intestinal microbiota changes were characterized using 16S rRNA gene sequencing. Results demonstrated that Baicalein ameliorated UC mice, particularly in high-dose of baicalein group. After baicalein treatment, the proinflammatory cytokines (TNF-α, IL-1β), and anti-inflammatory cytokine (IL-10) has decreased. Additionally, high-dose of baicalein strongly reversed oxidative stress alterations caused by DSS, as evidenced by Fe, MDA, ROS significantly depleted, and MPO, SOD, GSH significantly increased. Protein and mRNA expression analyses revealed that high-dose baicalein upregulated the expression of FTH1, GPX4, SLC7A11, SLC3A2 and Nrf2, while downregulating ACSL4 significantly. Microbiological analysis showed that baicalein ameliorated intestinal dysbiosis, increased Ligilactobacillus and NK4A136, while reduced _sensu_stricto_1 and Escherichia-Shigella. These findings suggest that baicalein mitigates DSS-induced UC mice by reducing oxidative stress and inflammation, suppressing ferroptosis and modulating gut microbiota composition, Proposing a potentially effective therapeutic approach for UC.
溃疡性结肠炎（UC）是一种非特异性炎症性疾病。黄芩苷在治疗UC方面具有潜在价值，但其机制尚不清楚。本研究旨在评估黄芩苷对葡聚糖硫酸钠（DSS）诱导的UC小鼠的保护作用。通过给予4% DSS溶液7天建立UC模型。治疗方法包括经口灌胃给予黄芩苷（10mg/kg、20mg/kg）和柳氮磺胺吡啶（200mg/kg）。通过体重、疾病活动指数（DAI）、组织病理学（苏木精-伊红染色）和结肠长度评估结肠损伤。通过酶联免疫吸附测定法测量炎性细胞因子，同时通过比色法分析氧化应激标志物和铁含量。通过蛋白质印迹法评估蛋白质表达，通过逆转录定量聚合酶链反应评估基因水平。使用16S rRNA基因测序表征肠道微生物群的变化。结果表明，黄芩苷改善了UC小鼠的状况，尤其是在高剂量黄芩苷组。黄芩苷治疗后，促炎细胞因子（TNF-α、IL-1β）和抗炎细胞因子（IL-10）减少。此外，高剂量黄芩苷强烈逆转了DSS引起的氧化应激改变，表现为铁、丙二醛、活性氧显著减少，髓过氧化物酶、超氧化物歧化酶、谷胱甘肽显著增加。蛋白质和mRNA表达分析显示，高剂量黄芩苷上调了FTH1、GPX4、SLC7A11、SLC3A2和Nrf2的表达，同时显著下调了ACSL4的表达。微生物学分析表明，黄芩苷改善了肠道菌群失调，增加了 Ligilactobacillus和NK4A136，同时减少了_sensu_stricto_1和埃希氏菌-志贺氏菌属。这些发现表明，黄芩苷通过减轻氧化应激和炎症、抑制铁死亡以及调节肠道微生物群组成来减轻DSS诱导的UC小鼠的症状，为UC提出了一种潜在有效的治疗方法。
