College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
Am J Chin Med. 2015;43(2):241-54. doi: 10.1142/S0192415X15500160. Epub 2015 Mar 19.
Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.
山奈酚是一种存在于多种植物中的具有生物活性的成分。山奈酚已被证明具有肝保护作用,可预防药物性肝损伤,但其对酒精性肝损伤(ALI)的作用尚不清楚。因此,本研究旨在评估山奈酚对小鼠 ALI 的作用。通过建立实验性 ALI 小鼠模型,并给予不同剂量的山奈酚处理 4 周,观察肝脏功能。通过监测血清中天冬氨酸氨基转移酶(AST/GOT)和丙氨酸氨基转移酶(ALT/GPT)水平、肝组织学研究、过氧化氢(H2O2)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的氧化应激、丙二醛(MDA)的脂质过氧化状态和血清中甘油三酯(TG)的脂质积累、以及体外和体内方法检测关键的微粒体酶细胞色素 2E1(CYP2E1)的表达水平和活性,来评估肝脏功能。未经处理的 ALI 小鼠表现出明显的肝损伤症状,如氧化应激、脂质过氧化和 CYP2E1 表达和活性过度增加。用不同剂量的山奈酚处理的小鼠表现出氧化应激和脂质过氧化显著减少,抗氧化防御活性增加。山奈酚治疗显著降低了肝 CYP2E1 的表达水平和活性,表明山奈酚可以下调 CYP2E1。这些发现表明,山奈酚通过减弱 CYP2E1 的活性和表达,并增强抗氧化防御系统的保护作用,对酒精性肝损伤具有肝保护作用。