Rutin improves spatial memory in Alzheimer's disease transgenic mice by reducing Aβ oligomer level and attenuating oxidative stress and neuroinflammation

Behav Brain Res. 2014 May 1;264:173-80. doi: 10.1016/j.bbr.2014.02.002. Epub 2014 Feb 7.


Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles in the brain. Aβ aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble Aβ oligomers are believed to be the most neurotoxic form among all forms of Aβ aggregates. We have previously reported a polyphenol compound rutin that could inhibit Aβ aggregation and cytotoxicity, attenuate oxidative stress, and decrease the production of nitric oxide and proinflammatory cytokines in vitro. In the current study, we investigated the effect of rutin on APPswe/PS1dE9 transgenic mice. Results demonstrated that orally administered rutin significantly attenuated memory deficits in AD transgenic mice, decreased oligomeric Aβ level, increased super oxide dismutase (SOD) activity and glutathione (GSH)/glutathione disulfide (GSSG) ratio, reduced GSSG and malondialdehyde (MDA) levels, downregulated microgliosis and astrocytosis, and decreased interleukin (IL)-1β and IL-6 levels in the brain. These results indicated that rutin is a promising agent for AD treatment because of its antioxidant, anti-inflammatory, and reducing Aβ oligomer activities.

Keywords: Alzheimer's disease; Neuroinflammation; Oligomer; Oxidative stress; Rutin; β-Amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Humans
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology*
  • Mice
  • Mice, Transgenic
  • Oxidative Stress / drug effects*
  • Presenilin-1 / genetics
  • Reaction Time
  • Rutin / pharmacology
  • Rutin / therapeutic use*
  • Time Factors


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • PSEN1 protein, human
  • Presenilin-1
  • Malondialdehyde
  • Rutin
  • Glutathione
  • Glutathione Disulfide