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根皮苷对异烟肼利福平诱导的小鼠肝损伤的肝保护作用通过调节 CYP450 和 Nrf2/HO-1 通路。

Hepatoprotective Effects of Phloridzin against Isoniazid-Rifampicin Induced Liver Injury by Regulating CYP450 and Nrf2/HO-1 Pathway in Mice.

机构信息

College of Medical Science, China Three Gorges University.

Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University.

出版信息

Chem Pharm Bull (Tokyo). 2022 Nov 1;70(11):805-811. doi: 10.1248/cpb.c22-00466. Epub 2022 Sep 8.

DOI:10.1248/cpb.c22-00466
PMID:36070932
Abstract

The protective effect of phloridzin (PHL) and its potential mechanism were examined in mice with liver injury induced by isoniazid (INH) and rifampicin (RFP). The mice were randomly divided into normal control group, model group, low (80 mg/kg), medium (160 mg/kg) and high (320 mg/kg) phloridzin-treated groups. After 28 d treatment, blood and liver tissue were collected and analysed. The results revealed that PHL regulated liver function related indicators and reduced the pathological tissue damage, indicating that PHL significantly alleviated the liver injury. Furthermore, the level of CYP450 enzyme, the expression of CYP3A4, CYP2E1, heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA and protein were inhibited by PHL. These results indicated that PHL exerts a protecting effect against liver injury induced by combination of RFP and INH. The potential mechanisms may be concerned with the activation of Nrf2/HO-1 signaling pathway containing its key antioxidant enzymes and regulation of CYP3A4 and CYP2E1.

摘要

研究了根皮苷(PHL)对异烟肼(INH)和利福平(RFP)诱导的肝损伤小鼠的保护作用及其潜在机制。将小鼠随机分为正常对照组、模型组、低(80mg/kg)、中(160mg/kg)和高(320mg/kg)PHL 处理组。治疗 28d 后,收集血液和肝脏组织进行分析。结果表明,PHL 调节肝功能相关指标,减轻肝组织病理损伤,表明 PHL 显著减轻肝损伤。此外,PHL 抑制 CYP450 酶水平、CYP3A4、CYP2E1、血红素加氧酶-1(HO-1)和核因子红细胞 2 相关因子 2(Nrf2)mRNA 和蛋白的表达。这些结果表明,PHL 对 RFP 和 INH 联合诱导的肝损伤具有保护作用。潜在的机制可能与包含其关键抗氧化酶的 Nrf2/HO-1 信号通路的激活以及 CYP3A4 和 CYP2E1 的调节有关。

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