Obovatol improves cognitive functions in animal models for Alzheimer's disease.
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 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 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.
College of Pharmacy and MRC, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, South Korea.
Dong-Young
DY
Choi
Jae Woong
JW
Lee
Jin
J
Peng
Young Jung
YJ
Lee
Jin-Yi
JY
Han
Yeon Hee
YH
Lee
Im Seop
IS
Choi
Sang Bae
SB
Han
Jae Kyung
JK
Jung
Woong Soo
WS
Lee
Seung-Ho
SH
Lee
Byoung-Mog
BM
Kwon
Ki-Wan
KW
Oh
Jin Tae
JT
Hong
D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000633:toxicity; D010647:Phenyl Ethers / Q000737:chemistry / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001713:Biphenyl Compounds; D010446:Peptide Fragments; D010647:Phenyl Ethers; C075222:amyloid beta-protein (1-42); C036795:obovatol; D053829:Amyloid Precursor Protein Secretases