探索急性肝损伤:减肥健康食品和CYP3A4诱导
Makiko Adachi1, Takeshi Kumagai2, Keiko Hosho3
1Department of Pharmacy, Tottori University Hospital, Yonago 683-8504, Japan.
Yonago acta medica
|May 28, 2024
概括
某些健康食品,如Coleus forskohlii,可以诱导细胞染色体P450 3A4 (CYP3A4) 酶活性. 这种诱导与服用多种药物和补充剂的患者的严重肝损伤有关.
科学领域:
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
- 毒理学 毒理学 毒理学
背景情况:
- 药物-药物和补充剂-药物相互作用可以在使用多种药物和健康食品的患者中引起急性肝炎.
- 研究健康食品和药物代谢相互作用的作用对于了解严重肝损伤至关重要.
- 细胞染色体P450 (CYP) 酶在药物代谢和潜在的毒性中发挥着关键作用.
研究的目的:
- 研究减肥保健食品提取物对药物代谢酶活性,特别是CYP的影响.
- 阐明药物诱导的肝损伤背后的分子机制.
- 评估各种健康食品成分的肝毒性.
主要方法:
- 使用HepG2细胞进行了细胞毒性测定,以评估暴露于健康食品提取物的细胞活力.
- 在工程3-1-10细胞中使用记者基因测试来评估CYP3A4诱导.
- 一个人性化的CYP3A/孕妇X受体 (PXR) 鼠标模型被用于确认体内CYP3A4诱导.
主要成果:
- 尼亚辛胺和Gymnema sylvestre提取物显著抑制了HepG2细胞活性的表现.
- 食补充剂A和Coleus forskohlii提取物显著诱导了CYP3A4记者活性.
- 在人性化的小鼠中,folskolin治疗导致CYP3A4mRNA表达的3.9倍增加.
结论:
- 科勒乌斯 Forskohlii 提取物表现出强大的 CYP3A4 基因的转录激活.
- 福斯科林是一种与Coleus forskohlii相关的成分,在相关的动物模型中诱导CYP3A4转录.
- 由Coleus forskohlii引起的CYP3A4诱导被认为是肝细胞损伤的原因,可能是通过乙氨基代谢.
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