...
首页> 外文期刊>Alcohol >14-Deoxyandrographolide alleviates ethanol-induced hepatosteatosis through stimulation of AMP-activated protein kinase activity in rats.
【24h】

14-Deoxyandrographolide alleviates ethanol-induced hepatosteatosis through stimulation of AMP-activated protein kinase activity in rats.

机译:14-脱氧花形照片通过在大鼠中刺激AMP活化的蛋白激酶活性来减轻乙醇诱导的肝胃蛋白病。

获取原文
获取原文并翻译 | 示例
           

摘要

Andrographis paniculata (AP) is a traditional medicinal plant of Ayurveda. It grows widely in Asia and is?prescribed in the treatment of liver diseases. Here we have investigated the beneficial role of 14-deoxyandrographolide (14-DAG), a bioactive diterpenoid from AP, against alcoholic steatosis in rats. 14-DAG was extracted from aerial parts (leaves and stems) of AP. Rats were fed with ethanol for 8 weeks. Animals were treated with 14-DAG during the last 4 weeks of ethanol treatment. In?vitro studies were undertaken in a human hepatocellular liver carcinoma cell line culture. Hepatosteatosis was assessed from histopathological studies of liver sections. Acetyl-CoA, malonyl-CoA, and triglyceride contents were determined using commercially available kits. Fatty acid synthesis was evaluated from incorporation of 1-(14)C acetate. Regulation of fatty acid oxidation and lipogenesis were monitored with immunoblotting and immunoprecipitation studies. Ethanol exposure led to hepatotoxicity, as evident from the marked enhancement in the levels of AST and ALT. The values decreased almost to control levels in response to 14-DAG treatment. Results showed that ethanol feeding induced deactivation of AMP-activated protein kinase (AMPK) that led to enhanced lipid synthesis and decreased fatty acid oxidation, culminating in hepatic fat accumulation. Treatment with 14-DAG activated AMPK through induction of cyclic AMP-protein kinase A pathway. Activation of AMPK was followed by down-regulation of sterol regulatory element binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, leading to suppression of lipogenesis. This was associated with up-regulation of sirtuin 1 and depletion of malonyl-CoA, in favor of increased fatty acid oxidation. 14-DAG controlled ethanol-induced hepatosteatosis by interfering with dysregulation of lipid metabolism. In conclusion, our results indicated that 14-DAG was capable of preventing the development of fatty liver through AMPK-mediated regulation of lipid metabolism. This finding supported the hepatoprotective role of 14-DAG, which might serve as a therapeutic option to alleviate hepatosteatosis in chronic alcoholism.
机译:Andrographis Paniculata(AP)是Ayurveda的传统药用植物。它在亚洲中广泛发展,是在治疗肝病的情况下。在这里,我们研究了14-脱氧花板(14-DAG),来自AP的生物活性二萜类化合物的有益作用,免受大鼠酒精性脂肪变性。从AP的空中零件(叶子和茎)中提取14-DAG。将大鼠用乙醇加入8周。在乙醇治疗的最后4周内用140℃进行动物治疗。在人类肝细胞癌细胞系培养中进行体外研究。从肝脏部分的组织病理学研究评估了肝胃病。使用市售试剂盒测定乙酰-CoA,丙酰基-CoA和甘油己烷内容物。通过掺入1-(14)C乙酸盐来评价脂肪酸合成。监测免疫印迹和免疫沉淀研究监测脂肪酸氧化和脂肪生成的调节。乙醇暴露导致肝毒性,从AST和ALT水平的显着增强中显而易见。响应于14-DAG处理,这些值几乎降低到控制水平。结果表明,乙醇喂养诱导的AMP活化蛋白激酶(AMPK)停用,其导致增强脂质合成和降低的脂肪酸氧化,最终在肝脂肪堆积中。通过诱导循环AMP-蛋白激酶A途径的途径用14-DAG活化AMP处理。随后的AMPK活化后调节甾醇调节元件结合蛋白-1C,乙酰基 - COA羧化酶和脂肪酸合成酶,导致抑制脂肪生成。这与Sirtuin1的上调和丙二酸的耗竭有关,有利于增加脂肪酸氧化。通过干扰脂质代谢的失调,14-DAG控制乙醇诱导的肝胃蛋白病变。总之,我们的结果表明,14-DAG能够通过AMPK介导的脂质代谢调节来预防脂肪肝的发育。这一发现支持14-DAG的肝保护作用,这可能是减轻慢性酗酒中肝胃蛋白病的治疗选择。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号