Objective： To investigate the cytoprotective effects of Saeng-kankunbi-tang（生肝健脾汤, SKT）, a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum, and its underlying mechanism involved...Objective： To investigate the cytoprotective effects of Saeng-kankunbi-tang（生肝健脾汤, SKT）, a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum, and its underlying mechanism involved. Methods： In mice, blood biochemistry and histopathology were assessed in carbon tetrachloride（CCl4）-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control, CCl4, SKT 500 mg/（kg·day） CCl4＋SKT 200 or 500 mg/（kg·day）. In Hep G2 cell, tert-butyl hydroperoxide（t BHP） induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-（4,5-dimethylthiazol）-2,5-diphenyltetrazolium bromide（MTT） assay, fluorescence activated cell sorting analysis and western blotting. Results： The administration of SKT prevented liver damage induced by CCl4 in mice, by inhibition of hepatocyte degeneration and inflammatory cell infiltration as well as plasma parameters such as alanine aminotransferase（P〈0.01）. Moreover, treatment with t BHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However, SKT pretreatment（30–300 μg/m L） reduced this cell death and oxidative stress（P〈0.01）. More importantly, SKT inhibited the ability of t BHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123（P〈0.01）. Furthermore, treatment with SKT induced extracellular signal-regulated kinases-mediated nuclear factor erythroid-2-related factor 2（Nrf2） activation as well as the expressions of heme oxygenase 1 and glutamate-cystein ligase catalytic, Nrf2 target genes. Conclusion： SKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.展开更多
文摘目的观察刺五加对酒精戒断大鼠焦虑行为的治疗作用并探讨其作用机制。方法雄性成年Sprague-Dawley大鼠40只,随机分为生理盐水对照组、酒精戒断模型组、刺五加低剂量(250 mg/kg)治疗组、刺五加高剂量(750 mg/kg)治疗组和刺五加高剂量对照组,每组各8只。给模型组、刺五加低剂量和高剂量治疗组腹腔注射酒精(20%,vol/vol),3 g/(kg·次),2次/d,共7 d,后停酒精3 d制备酒精戒断焦虑症模型;对照组注射等容积生理盐水。在3 d的戒断期,分别给大鼠灌胃刺五加或自来水,1次/d,共3 d。第3天灌胃1 h后,大鼠分别先后在旷场和高架十字迷宫进行行为测试;后收集血液,ELISA检测血浆中皮质酮浓度;收集大脑终纹床核(The bed nucleus of the stria terminalis,BNST),高效液相色谱法检测BNST的去甲肾上腺素水平。结果在旷场实验,与生理盐水对照组相比,酒精戒断模型组大鼠在旷场中央区的活动路程及时间明显减少;在高架十字迷宫实验,酒精戒断模型组大鼠的开臂进入次数和滞留时间百分比明显降低。ELISA结果显示,酒精戒断大鼠血浆中皮质酮浓度明显升高,而刺五加治疗抑制此升高。高效液相检测发现,刺五加治疗显著降低酒精戒断所致大鼠BNST去甲肾上腺素水平的增高。结论刺五加可改善酒精戒断大鼠焦虑行为,其作用机制可能与降低BNST去甲肾上腺素水平继而抑制血液中皮质酮浓度升高有关。
基金Supported by the National Research Foundation of Korea Grant funded by the Korea government(No.2014R1A2A2A01007375,No.2012R1A5A2A42671316)
文摘Objective： To investigate the cytoprotective effects of Saeng-kankunbi-tang（生肝健脾汤, SKT）, a herbal prescription consisting of Artemisia capillaris and Alisma canaliculatum, and its underlying mechanism involved. Methods： In mice, blood biochemistry and histopathology were assessed in carbon tetrachloride（CCl4）-induced oxidative hepatic injury in vivo. The animal groups included vehicle-treated control, CCl4, SKT 500 mg/（kg·day） CCl4＋SKT 200 or 500 mg/（kg·day）. In Hep G2 cell, tert-butyl hydroperoxide（t BHP） induced severe oxidative stress and mitochondrial dysfunction in vitro. The cyto-protective effects of SKT were determined by 3-（4,5-dimethylthiazol）-2,5-diphenyltetrazolium bromide（MTT） assay, fluorescence activated cell sorting analysis and western blotting. Results： The administration of SKT prevented liver damage induced by CCl4 in mice, by inhibition of hepatocyte degeneration and inflammatory cell infiltration as well as plasma parameters such as alanine aminotransferase（P〈0.01）. Moreover, treatment with t BHP induced hepatocyte death and cellular reactive oxygen species production in hepatocyte cell line. However, SKT pretreatment（30–300 μg/m L） reduced this cell death and oxidative stress（P〈0.01）. More importantly, SKT inhibited the ability of t BHP to induce changes in mitochondrial membrane transition in cell stained with rhodamine 123（P〈0.01）. Furthermore, treatment with SKT induced extracellular signal-regulated kinases-mediated nuclear factor erythroid-2-related factor 2（Nrf2） activation as well as the expressions of heme oxygenase 1 and glutamate-cystein ligase catalytic, Nrf2 target genes. Conclusion： SKT has the ability to protect hepatocyte against oxidative stress and mitochondrial damage mediated by Nrf2 activation.
