Obovatol improves cognitive functions in animal models for Alzheimer's disease = 오보바톨의 치매 치료 효과 및 기전

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Title
Obovatol improves cognitive functions in animal models for Alzheimer's disease = 오보바톨의 치매 치료 효과 및 기전
Author(s)
D Y Choi; J W Lee; J Peng; Y J Lee; J Y Han; Y H Lee; I S Choi; S B Han; J K Jung; W S Lee; S H Lee; Byoung-Mog Kwon; K W Oh; J T Hong
Bibliographic Citation
Journal of Neurochemistry, vol. 120, no. 6, pp. 1048-1059
Publication Year
2012
Abstract
Etiology of Alzheimer's disease (AD) is obscure, but neuroinflammation and accumulation of β-amyloid (Ab) are implicated in pathogenesis of AD. We have shown anti-inflammatory and neurotrophic properties of obovatol, a biphenolic compound isolated from Magnolia obovata. In this study, we examined the effect of obovatol on cognitive deficits in two separate AD models: (i) mice that received intracerebroventricular (i.c.v.) infusion of Aβ 1-42 (2.0 μg/mouse) and (ii) Tg2576 mice-expressing mutant human amyloid precursor protein (K670N, M671L). Injection of Aβ 1-42 into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. Aβ 1-42-induced abnormality was significantly attenuated by administration of obovatol. When we analyzed with Tg2576 mice, long-term treatment of obovatol (1 mg/kg/ day for 3 months) significantly improved cognitive function. In parallel with the improvement, treatment suppressed astroglial activation, BACE1 expression and NF-κB activity in the transgenic mice. Furthermore, obovatol potently inhibited fibrillation of Aβ in vitro in a dose-dependent manner, as determined by Thioflavin T fluorescence and electron microscopic analysis. In conclusion, our data demonstrated that obovatol prevented memory impairments in experimental AD models, which could be attributable to amelioration of neuroinflammation and amyloidogenesis by inhibition of NF-κB signaling pathway and anti-fibrillogenic activity of obovatol.
Keyword
Alzheimer's diseaseAmyloid-betaNeuroinflammationNF-kappaBObovatolTg2576
ISSN
0022-3042
Publisher
Wiley
DOI
http://dx.doi.org/10.1111/j.1471-4159.2011.07642.x
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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