College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, People's Republic of China.
State Key Laboratory of Chinese Pharmacies of Fujian Provincial Department of Science and Technology, Fujian University of Traditional Chinese Medicine, No. 1 Qiuyang Road, Shangjie Minhou, Fuzhou, 350122, Fujian, People's Republic of China.
Neurochem Res. 2018 May;43(5):1003-1009. doi: 10.1007/s11064-018-2507-x. Epub 2018 Mar 21.
Stroke involves numerous pathophysiological processes and oxidative stress is considered as a main cellular event in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a key role in inducing phase II detoxifying enzymes and antioxidant proteins and is now considered as a interesting therapeutic target for the treatment of stroke. The objective of this study is to investigate the protective effect of Gualou Guizhi granule (GLGZG) against oxidative stress and explore the protective mechanism of the Nrf2/ARE pathway. In vivo, administration of GLGZG in a rat model of focal cerebral ischemia significantly suppressed oxidative injury by increasing the activity of superoxide dismutase and glutathione level and decreasing reactive oxygen species and malondialdehyde levels. Western blot analysis showed that GLGZG induced nuclear translocation of Nrf2, and combined with real-time PCR results, which indicated that GLGZG up-regulated the Nrf2/ARE pathway. In addition, in cultured PC12 cells, GLGZG protected against HO induced oxidative injury and activated the Nrf2/ARE pathway. All the results demonstrated that GLGZG in the management of cerebral ischemia and HO induced oxidative injury may be associated with activation of Nrf2/ARE signaling pathway.
中风涉及多种病理生理过程，氧化应激被认为是其发病机制中的主要细胞事件。核因子红细胞 2 相关因子 2（Nrf2）/抗氧化反应元件（ARE）途径在诱导 II 相解毒酶和抗氧化蛋白方面起着关键作用，现在被认为是治疗中风的一个有趣的治疗靶点。本研究旨在探讨瓜蒌桂枝颗粒（GLGZG）对氧化应激的保护作用，并探讨 Nrf2/ARE 途径的保护机制。在体内，GLGZG 在局灶性脑缺血大鼠模型中的给药通过增加超氧化物歧化酶的活性和谷胱甘肽水平以及降低活性氧和丙二醛水平来显著抑制氧化损伤。Western blot 分析表明，GLGZG 诱导 Nrf2 的核转位，并且结合实时 PCR 结果表明，GLGZG 上调了 Nrf2/ARE 途径。此外，在培养的 PC12 细胞中，GLGZG 可抵抗 HO 诱导的氧化损伤并激活 Nrf2/ARE 途径。所有结果表明，GLGZG 在管理脑缺血和 HO 诱导的氧化损伤方面可能与 Nrf2/ARE 信号通路的激活有关。
