title: Orientin alleviates cognitive deficits and oxidative stress in Aβ1-42-induced mouse model of Alzheimer's disease.
abstract: OBJECTIVE
  β-Amyloid (Aβ)-mediated neurotoxicity plays a critical role in the pathogenesis of Alzheimer's disease (AD), possibly including Aβ-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 Ori can activate Nrf2/HO-1 signaling and alleviate apoptosis induced by Aβ1-42, and ameliorate cognitive deficits in AD mice.
  
  
  METHODS
  AD models were made by injecting Aβ1-42 into the bilateral hippocampus of mice. The mice were randomly assigned to three groups: the normal mice and Aβ1-42-induced AD mice with saline, and Aβ1-42-induced AD mice with Ori (5mg/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.
  
  
  RESULTS
  Results indicated that Ori 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 Ori treatment. In addition, the current study showed that Ori could attenuate mitochondrial dysfunction induced by Aβ1-42, and subsequently inhibited the mitochondrial apoptotic pathway. Ori induced the nuclear translocation of Nrf2, which enhanced the expression of HO-1 and activation of the redox signaling pathway.
  
  
  CONCLUSIONS
  Ori might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD.
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Linjie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, PR China.
authors.forename: Sulei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China. Electronic address: xuyun20042001@aliyun.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, PR China. Electronic address: zhuquelee@126.com.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D005419:Flavonoids / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005960:Glucosides / Q000627:therapeutic use*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D016166:Free Radical Scavengers; D005960:Glucosides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D051547:Heme Oxygenase-1; C065886:orientin
keywords: Alzheimer's disease; Nrf2/HO-1 pathway; Orientin; Oxidative stress; β-Amyloid