Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2
Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2
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DOI：
10.1142/s0192415x18500246
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发表时间：
2018-01-01
影响因子：
5.7
通讯作者：
Kim, Sang Chan
中科院分区：
文献类型：
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作者：
Jung, Ji Yun;Park, Sang Mi;Kim, Sang Chan
活性氧引起的氧化应激是各种肝脏疾病的主要原因。研究朝鲜淫羊藿水提取物（EKE）对花生四烯酸（AA）+铁离子介导的HepG 2细胞毒性和四氯化碳（CCl 4-）介导的小鼠急性肝损伤的保护作用。EKE（30和100 μ g/mL）预处理显着抑制AA+ Niron介导的HepG 2细胞的细胞毒性，通过防止裂解的caspase-3和聚（ADP-核糖）聚合酶的表达的变化。EKE减弱过氧化氢的产生，谷胱甘肽耗竭，线粒体膜功能障碍。EKE还增加核因子红细胞2相关因子2（Nrf 2）的核转位，反式激活具有荧光素酶活性的抗氧化反应元件，并诱导抗氧化基因的表达。此外，在Nrf 2敲除细胞中，EKE对AA+铁的细胞保护作用被阻断。超高效液相色谱分析表明，EKE含有淫羊藿苷，淫羊藿苷，槲皮素，淫羊藿苷和槲皮素都被发现保护HepG 2细胞从AA+铁通过Nrf 2激活。在CCl 4诱导的小鼠肝损伤模型中，连续4天给予EKE（300 mg/kg）预处理可改善CCl 4介导的血清天冬氨酸转氨酶活性、组织学活性指数、肝实质变性和炎性细胞浸润的增加。EKE还减少了肝组织中硝基酪氨酸、4-羟基壬烯醛、切割的caspase-3和切割的聚（ADP-核糖）聚合酶阳性细胞的数量。这些结果表明，EKE是通过Nrf 2激活预防或治疗氧化应激相关肝病的有希望的候选者。
Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)+iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100 mu g/mL) significantly inhibited AA+Niron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA+iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA+iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300 mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.