Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy
Glycycoumarin ameliorates alcohol-induced hepatotoxicity via activation of Nrf2 and autophagy
复制标题
DOI：
10.1016/j.freeradbiomed.2015.07.006
复制
发表时间：
2015-12-01
影响因子：
7.4
通讯作者：
Hu, Hongbo
中科院分区：
文献类型：
--
作者：
Song, Xinhua;Yin, Shutao;Hu, Hongbo
甘草是一种传统的中药，几个世纪以来一直被用来治疗各种疾病，包括肝病。然而，甘草生物学功能的化学基础和生物学机制仍然难以捉摸。本研究的目的是测试甘氨香豆素（GCM），甘草香豆素的代表，使用慢性和急性酒精性肝损伤的动物模型的肝保护作用。采用C57 BL/6 J小鼠，观察GCM对慢性或急性乙醇暴露所致肝损伤的保护作用。利用AML-12和HepG 2细胞来确定Nrf 2在GCM的肝保护作用中的功能作用，并破译GCM诱导的Nrf 2活化的机制。我们发现，GCM治疗导致慢性或急性乙醇暴露的肝毒性显着降低。进一步的机制研究表明，Nrf 2通过p38通路的激活和GCM诱导自噬有助于其肝保护活性。此外，我们证明，p62上调的转录机制也有助于Nrf 2激活通过一个正反馈回路。我们的研究已经确定GCM作为一种新的活性成分，有助于甘草的保肝活性。(C)由Elsevier Inc.出版。
Licorice, a traditional Chinese medicine, has been used to treat various diseases, including liver disease, for centuries. However, the chemical basis and biological mechanisms underlying the biological functions of licorice remain elusive. The purpose of the current study was to test the hepatoprotective effect of glycycoumarin (GCM), a representative coumarin in licorice, using animal models of both chronic and acute alcoholic liver injury. C57BL/6J mice were used to evaluate the hepatoprotective effect of GCM on liver injury induced by either chronic or acute ethanol exposure. AML-12 and HepG2 cells were utilized to determine the functional role of Nrf2 in the hepatoprotective effect of GCM and to decipher the mechanisms of GCM-induced Nrf2 activation. We found that treatment with GCM leads to a significant reduction in hepatotoxicity in response to either chronic or acute ethanol exposure. Further mechanistic investigations reveal that activation of Nrf2 via the p38 pathway and induction of autophagy by GCM contribute to its hepatoprotective activity. In addition, we demonstrate that p62 upregulation by a transcriptional mechanism also contributes to Nrf2 activation via a positive feedback loop. Our study has identified GCM as a novel active ingredient that contributes to the hepatoprotective activity of licorice. (C) 2015 Published by Elsevier Inc.