期刊
LIFE SCIENCES
卷 121, 期 -, 页码 104-109出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2014.11.021
关键词
Alzheimer's disease; beta-Amyloid; Oxidative stress; Nrf2/HO-1 pathway; Orientin
资金
- National Nature Science Foundation of China [81200839, 81230026, 81171085]
- Natural Science Foundation [BL2012013]
- Bureau of Health of the Jiangsu Province of China [LJ201101]
Aims: beta-Amyloid (A beta)-mediated neurotoxicity plays a critical role in the pathogenesis of Alzheimer's disease (AD), possibly including A beta-induced mitochondrial dysfunction and oxidative stress. Previous studies have demonstrated that orientin (Ori) possesses antioxidation capabilities in vitro. Therefore, current study is to demonstrate that On can activate Nrf2/HO-1 signaling and alleviate apoptosis induced by A beta(1-42), and ameliorate cognitive deficits in AD mice. Main methods: AD models were made by injecting A beta(1-42) into the bilateral hippocampus of mice. The mice were randomly assigned to three groups: the normal mice and A beta(1-42)-induced AD mice with saline, and A beta(1-42)induced AD mice with Ori (5 mg/kg), and were injected intraperitoneally once a day for 15 days. After the Morris Water Maze (MWM) test, mice were sacrificed and brains were harvested for biochemical analysis. Key findings: Results indicated that On could ameliorate cognitive deficits in AD mice. Levels of oxidative stress, indicated by production of reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), 4-hydroxy-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were significantly decreased after On treatment. in addition, the current study showed that On could attenuate mitochondrial dysfunction induced by A beta(1-42), and subsequently inhibited the mitochondrial apoptotic pathway. On induced the nuclear translocation of Nr12, which enhanced the expression of HO-1 and activation of the redox signaling pathway. Significance: On might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD. (C) 2014 Elsevier Inc. All rights reserved.
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