通过调节Nrf2信号,Scutellarin通过促进细胞抗氧化能力来抑制铁
Haiyan Yang1,2, Onkei Chan1,2, Xiaodi Huang1
1Department of Immunology and Microbiology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
Acta biochimica et biophysica Sinica
|August 20, 2025
概括
一种天然的黄类化合物斯库特拉林抑制铁亡,这是导致急性损伤 (AKI) 的细胞死亡途径. 这种化合物通过激活Nrf2信号通路,减少氧化应激和脂质过氧化来保护AKI.
科学领域:
- 生物化学
- 细胞生物学
- 药理学
背景情况:
- 铁死是一种受控的细胞死亡途径,由铁依赖的脂质过氧化驱动,与急性损伤 (AKI) 等疾病有关.
- 斯库特拉林是一种来自Erigeron breviscapus的类,具有抗炎和抗氧化作用,但其在ferroptosis中的作用尚不清楚.
研究的目的:
- 检查斯库特拉林是否可以抑制铁.
- 阐明斯库特拉林作用的基本分子机制.
- 在AKI模型中评估scutellarin的治疗潜力.
主要方法:
- 在实验室中使用人类HK-2细胞和小鼠巨细胞治疗铁死诱导剂 (RSL3,埃拉斯).
- 评估线粒体功能,活性氧物种 (ROS) 生成和Nrf2信号通路的激活.
- 使用叶酸诱导的AKI小鼠模型进行体内研究,评估损伤和铁死标志物.
主要成果:
- 在细胞培养中抑制铁,抵消线粒体功能障碍和ROS生成.
- 斯库特拉林治疗增加了核Nrf2水平及其向基因 (HO-1,GPX4) 的表达,而Nrf2抑制剂布鲁萨托尔则阻断了这种作用.
- 在体内,斯库特拉林在AKI模型中缓解了损伤,降低了像4-hydroxynonenal (4-HNE) 这样的铁损伤标志物.
结论:
- 通过抗氧化机制有效抑制铁.
- Nrf2信号通路对于皮质素的铁抑制作用至关重要.
- 通过抑制铁亡,斯库特拉林具有缓解急性损伤的治疗潜力.
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