Stilbenoids from Rheum undulatum Protect Hepatocytes Against Oxidative Stress Through AMPK Activation
Stilbenoids from Rheum undulatum Protect Hepatocytes Against Oxidative Stress Through AMPK Activation
复制标题
DOI：
10.1002/ptr.5442
复制
发表时间：
2015-10-01
影响因子：
7.2
通讯作者：
Ryu, Jae-Ha
中科院分区：
文献类型：
--
作者：
Dong, Guang-zhi;Lee, Yu-ih;Ryu, Jae-Ha
氧化应激促进了几种疾病，包括肝病。本研究从波叶大黄中分离得到了几种二苯乙烯类化合物，并对其保肝活性和作用机制进行了初步研究。从R. undulatum保护肝细胞免受花生四烯酸+铁（AA + Fe）诱导的氧化应激。其中化合物5的活性最强。三甲氧基芪类化合物（化合物6）显示出最好的保护HepG2细胞免受AA + Fe诱导的氧化应激的活性，而反式芪类化合物（化合物7）显示出较弱的活性。这些芪类化合物抑制AA + Fe处理的HepG2细胞中的ROS产生，并且还抑制AA + Fe诱导的MMP破坏。它们对AA + Fe诱导的MMP破坏的保护作用被AMP激活的蛋白激酶（AMPK）抑制剂、化合物C或转染显性阴性形式的AMPK处理所废除。综上所述，R. undulatum通过激活AMPK保护肝细胞免受AA + Fe诱导的氧化应激。芳基中的甲氧基对于它们的细胞保护活性是重要的。版权所有（c）2015约翰威利父子有限公司
Oxidative stress promotes several diseases, including liver disease. We have isolated several stilbenoids from Rheum undulatum to investigate their hepatoprotective activities and mechanism. Stilbenoids from R. undulatum protects hepatocytes against arachidonic acid + iron (AA + Fe) induced oxidative stress. Pterostilbene (compound 5) shows stronger activity than the others. Trimethoxystilbenoid (compound 6) shows best activity on protection of HepG2 cells from AA + Fe-induced oxidative stress, and trans-stilbenoid (compound 7) shows weak activity. These stilbenoids suppress ROS generation in AA + Fe-treated HepG2 cells and also suppress AA + Fe-induced MMP disruption. Their protective effects on AA + Fe-induced MMP disruption were abrogated by treatment of AMP-activated protein kinase (AMPK) inhibitor, compound C or transfection of dominant negative form of AMPK. Taken together, stilbenoids from R. undulatum protect hepatocytes against AA + Fe-induced oxidative stress through AMPK activation. And the methoxy groups in the aryl groups are important for their cytoprotective activity. Copyright (c) 2015 John Wiley & Sons, Ltd.