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

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

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

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 50. mg/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.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalBehavioural Brain Research
Volume250
DOIs
Publication statusPublished - 01-08-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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