Nobiletin, a citrus flavonoid, improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of Alzheimer's disease (3XTg-AD).

Abstract

Alzheimer's disease (AD), the most common form of dementia among the elderly, is characterized by the progressive decline of cognitive function. Increasing evidence indicates that the production and accumulation of amyloid β (Aβ), particularly soluble Aβ oligomers, is central to the pathogenesis of 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, NMDA receptor antagonist-treated mice, and senescence-accelerated mouse prone 8. Here, we present evidence that this natural compound improves cognitive impairment and reduces soluble Aβ levels in a triple transgenic mouse model of AD (3XTg-AD) that progressively develops amyloid plaques, neurofibrillary tangles, and cognitive impairments. Treatment with nobiletin (30 mg/kg) for 3 months reversed the impairment of short-term memory and recognition memory in 3XTg-AD mice. Our ELISA analysis also showed that nobiletin reduced the levels of soluble Aβ1-40 in the brain of 3XTg-AD mice. Furthermore, nobiletin reduced ROS levels in the hippocampus of 3XTg-AD as well as wild-type mice. These results suggest that this natural compound has potential to become a novel drug for the treatment and prevention of AD.

• Authors: Akira Nakajima, Yuki Aoyama, Eun-Joo Shin, Yunsung Nam, Hyoung-Chun Kim, Taku Nagai, Akihito Yokosuka, Yoshihiro Mimaki, Tsuyoshi Yokoi, Yasushi Ohizumi, Kiyofumi Yamada
• Journal: Behavioural brain research (Behav Brain Res) Vol. 289 Pg. 69-77 (Aug 01 2015) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 25913833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Flavones
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• nobiletin

Topics

• Alzheimer Disease (drug therapy, metabolism, psychology)
• Amyloid beta-Peptides (analysis)
• Animals
• Avoidance Learning (drug effects)
• Brain (drug effects, enzymology, metabolism)
• Disease Models, Animal
• Flavones (administration & dosage)
• Male
• Maze Learning (drug effects)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Motor Activity (drug effects)
• Oxidative Stress (drug effects)
• Peptide Fragments (analysis)
• Recognition, Psychology (drug effects)