Nobiletin, a citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse.

Abstract

Senescence-accelerated mouse prone 8 (SAMP8) is a model of aging characterized by the early onset of learning and memory impairment and various pathological features of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, ameliorates learning and memory impairment in olfactory-bulbectomized mice, amyloid precursor protein transgenic mice, and NMDA receptor antagonist-treated mice. Here, we present evidence that this natural compound improves age-related cognitive impairment and reduces oxidative stress and tau phosphorylation in SAMP8 mice. Treatment with nobiletin (10 or 50mg/kg) reversed the impairment of recognition memory and context-dependent fear memory in SAMP8 mice. Treatment with nobiletin also restored the decrease in the GSH/GSSG ratio in the brain of SAMP8 mice. In addition, increases in glutathione peroxidase and manganese-superoxide dismutase activities, as well as a decrease in protein carbonyl level, were observed in the brain of nobiletin-treated SAMP8 mice. Furthermore, nobiletin reduced tau phosphorylation in the hippocampus of SAMP8 mice. Together, the markedly beneficial effects of nobiletin represent a potentially useful treatment for ameliorating the learning and memory deficits, oxidative stress, and hyperphosphorylation of tau in aging as well as age-related neurodegenerative diseases such as AD.

• Authors: Akira Nakajima, Yuki Aoyama, Thuy-Ty Lan Nguyen, Eun-Joo Shin, Hyoung-Chun Kim, Shinnosuke Yamada, Tsuyoshi Nakai, Taku Nagai, Akihito Yokosuka, Yoshihiro Mimaki, Yasushi Ohizumi, Kiyofumi Yamada
• Journal: Behavioural brain research (Behav Brain Res) Vol. 250 Pg. 351-60 (Aug 01 2013) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 23714077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Flavones
• tau Proteins
• nobiletin
• Glutathione Peroxidase
• Superoxide Dismutase
• Glutathione

Topics

• Aging (drug effects, genetics, physiology)
• Analysis of Variance
• Animals
• Antioxidants (chemistry, pharmacology, therapeutic use)
• Body Weight (drug effects, genetics)
• Case-Control Studies
• Cognition Disorders (drug therapy)
• Conditioning, Psychological (drug effects, physiology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Exploratory Behavior (drug effects)
• Fear (drug effects, physiology)
• Flavones (chemistry, pharmacology, therapeutic use)
• Glutathione (metabolism)
• Glutathione Peroxidase (genetics, metabolism)
• Lipid Metabolism (drug effects)
• Male
• Maze Learning (drug effects, physiology)
• Mice
• Mice, Transgenic
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Protein Carbonylation (drug effects)
• Superoxide Dismutase (genetics, metabolism)
• tau Proteins (metabolism)