Nobiletin, a citrus flavonoid, improves memory impairment and Aβ pathology in a transgenic mouse model of Alzheimer's disease

Hiroshi Onozuka, Akira Nakajima, Kentaro Matsuzaki, Ryong Woon Shin, Koichi Ogino, Daisuke Saigusa, Naomi Tetsu, Akihito Yokosuka, Yutaka Sashida, Yoshihiro Mimaki, Tohru Yamakuni, Yasushi Ohizumi

Research output: Contribution to journalArticlepeer-review

161 Citations (Scopus)

Abstract

Increasing evidence suggests that the elevation of β-amyloid (Aβ) peptides in the brain is central to the pathogenesis of Alzheimer's disease (AD). Our recent studies have demonstrated that nobiletin, a polymethoxylated flavone from citrus peels, enhances cAMP/protein kinase A/extracellular signal-regulated kinase/cAMP response element-binding protein signaling in cultured hippocampal neurons and ameliorates Aβ-induced memory impairment in AD model rats. For the first time, we report that this natural compound improves memory deficits in amyloid precursor protein (APP) transgenic mice that overexpress human APP695 harboring the double Swedish and London mutations [APP-SL 7-5 transgenic (Tg) mice]. Our enzyme-linked immunosorbent assay (ELISA) also showed that administration of nobiletin to the transgenic mice for 4 months markedly reduced quantity of guanidine-soluble Aβ1-40 and Aβ1-42 in the brain. Furthermore, consistent with the results of ELISA, by immunohistochemistry with anti-Aβ antibody, it was evidently shown that the administration of nobiletin decreased the Aβ burden and plaques in the hippocampus of APP-SL 7-5 Tg mice. These findings suggest that this natural compound has potential to become a novel drug for fundamental treatment of AD.

Original languageEnglish
Pages (from-to)739-744
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume326
Issue number3
DOIs
Publication statusPublished - 2008 Sep

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Nobiletin, a citrus flavonoid, improves memory impairment and Aβ pathology in a transgenic mouse model of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this