Department of Microbiology and Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Environ Toxicol Pharmacol. 2011 Jan;31(1):233-41. doi: 10.1016/j.etap.2010.11.002. Epub 2010 Nov 9.
This study investigated the cytoprotective effect of baicalein (5,6,7-trihydroxyflavone) against oxidative stress-induced mitochondrial dysfunction. Electron spin resonance (ESR) spectrometry revealed that baicalein showed significant scavenging effects on superoxide radicals and hydroxyl radicals. When H(2)O(2) treatment induces an increase in mitochondrial reactive oxygen species (ROS), baicalein treatment decreased high level of ROS. Baicalein significantly reduced alteration of Bcl-2 family proteins, the release of cytochrome c from mitochondria into the cytosol via inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1) and c-Jun NH(2)-terminal kinase (JNK) cascades induced by H(2)O(2) treatment. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme in mitochondria against oxidative stress. Baicalein restored both MnSOD protein expression and activity, which were abolished by H(2)O(2) treatment. The transcription factor NF-E2-related factor 2 (Nrf2) is a critical regulator of MnSOD, achieved by binding to the antioxidant response element (ARE). Baicalein restored nuclear Nrf2 protein expression and its ARE binding activity, which were abolished by H(2)O(2) treatment. These studies demonstrate that baicalein attenuates mitochondrial oxidative stress by activating Nrf2-mediated MnSOD induction.
本研究探讨了黄芩素（5,6,7-三羟基黄酮）对氧化应激诱导的线粒体功能障碍的细胞保护作用。电子自旋共振（ESR）光谱表明，黄芩素对超氧自由基和羟自由基具有显著的清除作用。当 H2O2 处理引起线粒体活性氧（ROS）增加时，黄芩素处理降低了高水平的 ROS。黄芩素通过抑制丝裂原活化蛋白激酶激酶-4（MKK4/SEK1）和 c-Jun NH2-末端激酶（JNK）级联反应，显著减少 Bcl-2 家族蛋白的改变、细胞色素 c 从线粒体释放到细胞质。H2O2 处理引起的。锰超氧化物歧化酶（MnSOD）是线粒体对抗氧化应激的重要抗氧化酶。黄芩素恢复了 MnSOD 蛋白表达和活性，而 H2O2 处理则使其丧失。转录因子 NF-E2 相关因子 2（Nrf2）是 MnSOD 的关键调节因子，通过与抗氧化反应元件（ARE）结合来实现。黄芩素恢复了核 Nrf2 蛋白表达及其 ARE 结合活性，而 H2O2 处理则使其丧失。这些研究表明，黄芩素通过激活 Nrf2 介导的 MnSOD 诱导来减轻线粒体氧化应激。
