Orientin alleviates cognitive deficits and oxidative stress in Aβ1-42-induced mouse model of Alzheimer's disease

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.