Obovatol improves cognitive functions in animal models for Alzheimer’s disease
Article first published online: 10 FEB 2012
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 120, Issue 6, pages 1048–1059, March 2012
How to Cite
Choi, D.-Y., Lee, J. W., Peng, J., Lee, Y. J., Han, J.-Y., Lee, Y. H., Choi, I. S., Han, S. B., Jung, J. K., Lee, W. S., Lee, S.-H., Kwon, B.-M., Oh, K.-W. and Hong, J. T. (2012), Obovatol improves cognitive functions in animal models for Alzheimer’s disease. Journal of Neurochemistry, 120: 1048–1059. doi: 10.1111/j.1471-4159.2011.07642.x
- Issue published online: 6 MAR 2012
- Article first published online: 10 FEB 2012
- Accepted manuscript online: 30 DEC 2011 10:41AM EST
- Received August 3, 2011; revised manuscript received December 23, 2011; accepted December 23, 2011.
- Alzheimer's disease;
J. Neurochem. (2012) 120, 1048–1059.
Etiology of Alzheimer’s disease (AD) is obscure, but neuroinflammation and accumulation of β-amyloid (Aβ) 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 Aβ1–42 (2.0 μg/mouse) and (ii) Tg2576 mice-expressing mutant human amyloid precursor protein (K670N, M671L). Injection of Aβ1–42 into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. Aβ1–42-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 Aβin 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.