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

Life Sci. 2015 Jan 15;121:104-9. doi: 10.1016/j.lfs.2014.11.021. Epub 2014 Dec 9.

Abstract

Aims: 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.

Main 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.

Key findings: 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.

Significance: Ori might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD.

Keywords: Alzheimer's disease; Nrf2/HO-1 pathway; Orientin; Oxidative stress; β-Amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / psychology
  • Amyloid beta-Peptides*
  • Animals
  • Apoptosis / drug effects
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Flavonoids / therapeutic use*
  • Free Radical Scavengers / therapeutic use*
  • Glucosides / therapeutic use*
  • Heme Oxygenase-1 / metabolism
  • Male
  • Maze Learning / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects*
  • Peptide Fragments*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Amyloid beta-Peptides
  • Flavonoids
  • Free Radical Scavengers
  • Glucosides
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Heme Oxygenase-1
  • orientin