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

Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular beta-amyloid (A beta) plaques and intracellular neurofibrillary tangles in the brain. A beta aggregation is closely associated with neurotoxicity, oxidative stress, and neuronal inflammation. The soluble A beta oligomers are believed to be the most neurotoxic form among all forms of A beta aggregates. We have previously reported a polyphenol compound rutin that could inhibit A beta 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 A beta 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)-1 beta 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 A beta oligomer activities. (C) 2014 Elsevier B.V. All rights reserved.