Obovatol improves cognitive functions in animal models for Alzheimer's disease

Title
Obovatol improves cognitive functions in animal models for Alzheimer's disease
Author(s)
최동영이재웅[이재웅]Jin Peng[Jin Peng]이영중[이영중]한진이[한진이]이연희[이연희]최임섭[최임섭]한상배[한상배]정재경[정재경]이웅수[이웅수]이승호[이승호]권병목[권병목]오기완[오기완]홍진태[홍진태]
Keywords
AMYLOID PRECURSOR PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MAGNOLIA BARK EXTRACT; FACTOR-KAPPA-B; BETA-SECRETASE; TRANSGENIC MICE; MOUSE MODEL; IN-VIVO; MEMORY IMPAIRMENT; PROMOTER ACTIVITY
Issue Date
201203
Publisher
WILEY-BLACKWELL
Citation
JOURNAL OF NEUROCHEMISTRY, v.120, no.6, pp.1048 - 1059
Abstract
Etiology of Alzheimers disease (AD) is obscure, but neuroinflammation and accumulation of beta-amyloid (A beta) 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 A beta 142 (2.0 mu g/mouse) and (ii) Tg2576 mice-expressing mutant human amyloid precursor protein (K670N, M671L). Injection of A beta 142 into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. A beta 142-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-?B activity in the transgenic mice. Furthermore, obovatol potently inhibited fibrillation of A beta 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-?B signaling pathway and anti-fibrillogenic activity of obovatol.
URI
http://hdl.handle.net/YU.REPOSITORY/29658http://dx.doi.org/10.1111/j.1471-4159.2011.07642.x
ISSN
0022-3042
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약학대학 > 약학부 > Articles
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