Key Laboratory of Biotechnology and Bioresources Utilization, Educational of Minister, College of Life Science, Dalian Nationalities University, Dalian 116600, China.
Jiamusi College, Heilongjiang University of Chinese Medicine, Jiamusi 154007, China.
Food Funct. 2019 Sep 1;10(9):5323-5332. doi: 10.1039/c9fo01481k. Epub 2019 Aug 7.
Oxidative stress is considered to play an important role in the cerebral ischemia-reperfusion injury. The nuclear transcription factor erythroid-2-related factor 2 (Nrf2)/NAD(P)H dehydrogenase [quinone] 1 (NQO1) pathway has been considered as a potential target for neuroprotection in cerebral ischemia-reperfusion injury. Nomilin (NOM) is a limonoid compound obtained from the extracts of citrus fruits. The purpose of our study was to determine whether NOM could exert beneficial effects in cerebral ischemia-reperfusion rats. Firstly, NOM treatment significantly mitigated cell death and decreased lactate dehydrogenase (LDH) release and ROS production in SH-SY5Y cells induced by oxygen-glucose deprivation (OGD), which was almost abolished by Nrf2 knockdown. Secondly, NOM improved infarct area, brain edema and neurological deficits in an experimental stroke rat model via middle cerebral artery occlusion (MCAO). Furthermore, NOM attenuated blood-brain barrier (BBB) disruption in MCAO rats, which might be associated with alleviating the loss of tight junction proteins, including ZO-1 and occludin-5. Further results revealed that NOM treatment effectively mitigated oxidative stress and facilitated the expressions of Nrf2 and NQO1, which might confirm that the loss of tight junction proteins in the microvasculature was likely mediated by oxidative stress. In conclusion, our study provided evidence that the protective effects of NOM in cerebral ischemia-reperfusion rats were related to the Nrf2/NQO1 pathway.
氧化应激被认为在脑缺血再灌注损伤中发挥重要作用。核转录因子红细胞 2 相关因子 2（Nrf2）/烟酰胺腺嘌呤二核苷酸（磷酸）脱氢酶[醌]1（NQO1）途径被认为是脑缺血再灌注损伤中神经保护的潜在靶点。诺米林（NOM）是从柑橘类水果提取物中获得的一种三萜类化合物。本研究旨在确定 NOM 是否对脑缺血再灌注大鼠具有有益作用。首先，NOM 处理可显著减轻氧葡萄糖剥夺（OGD）诱导的 SH-SY5Y 细胞死亡和乳酸脱氢酶（LDH）释放及 ROS 产生，而 Nrf2 敲低则几乎消除了这种作用。其次，NOM 通过大脑中动脉闭塞（MCAO）改善了实验性中风大鼠模型中的梗死面积、脑水肿和神经功能缺损。此外，NOM 减轻了 MCAO 大鼠血脑屏障（BBB）的破坏，这可能与减轻紧密连接蛋白（包括 ZO-1 和 occludin-5）的丢失有关。进一步的结果表明，NOM 处理可有效减轻氧化应激，并促进 Nrf2 和 NQO1 的表达，这可能证实微血管中紧密连接蛋白的丢失可能是由氧化应激介导的。总之，本研究提供的证据表明，NOM 对脑缺血再灌注大鼠的保护作用与 Nrf2/NQO1 途径有关。
