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Scutellaria baicalensis Extracts Restrict Intestinal Epithelial Cell Ferroptosis by Regulating Lipid Peroxidation and GPX4/ACSL4 in Colitis.

作者:Jingyan Zhang, Bingyan Tan, Hong Wu, Tai Han, Dan Fang, H. Cai, Bing Hu, An Kang · 发表于:Phytomedicine · 年份:2025 · DOI:10.1016/j.phymed.2025.156708 · 被引用次数:54 · 研究领域:Medicine

BACKGROUND Ferroptosis in colonic epithelial cells has been implicated in the development of ulcerative colitis (UC) and the accompanying gut leakage. Scutellaria baicalensis Georgi (Scu) is widely used herb medicine for alleviating UC. PURPOSE We aimed to clarify the therapeutic effect of Scu on UC by inhibiting intestinal epithelial cell ferroptosis and explore its regulatory mechanisms on lipid peroxidation and the GPX4/ACSL4 pathways. METHODS UPLC-Q-TOF/MS was employed to analyze chemicals in the herbal extract and the colonic exposure of prototypes in Scu-treated mice. Additionally, the main compounds were quantified using HPLC-UV. The ameliorative effects of Scu were comprehensively explored in a UC mouse model established by feeding with dextran sulfate sodium (DSS). HPLC-MS based metabolomic studies were conducted to identify the differential metabolites in colon tissues from Scu or vehicle treated UC mice. Network pharmacology was conducted for target prediction and potential pathway analysis. In conjunction with these bioinformatic analyses, we performed RT-qPCR, immunofluorescence, immunohistochemistry and immunoblotting to elucidate the regulatory mechanisms of Scu on ferroptosis-related pathways in both in vivo and in vitro models. RESULTS 78 chemical constituents in Scu were characterized, with 42 detected in the colonic tissues of Scu-treated mice. Scu could alleviate UC related symptoms in mice, including increased colon length and decreased pathological...