title: Obovatol attenuates LPS-induced memory impairments in mice via inhibition of NF-κB signaling pathway.
abstract: Neuroinflammation and accumulation of β-amyloid are critical pathogenic mechanisms of Alzheimer's disease (AD). In the previous study, we have shown that systemic lipopolysaccharide (LPS) caused neuroinflammation with concomitant increase in β-amyloid and memory impairments in mice. In an attempt to investigate anti-neuroinflammatory properties of obovatol isolated from Magnolia obovata, we administered obovatol (0.2, 0.5 and 1.0 mg/kg/day, p.o.) to animals for 21 days before injection of LPS (0.25 mg/kg, i.p.). We found that obovatol dose-dependently attenuates LPS-induced memory deficit in the Morris water maze and passive avoidance tasks. Consistent with the results of memory tasks, the compound prevented LPS-induced increases in Aβ₁₋₄₂ formation, β- and γ-secretases activities and levels of amyloid precursor protein, neuronal β-secretase 1 (BACE1), and C99 (a product of BACE1) in the cortex and hippocampus. The LPS-mediated neuroinflammation as determined by Western blots and immunostainings was significantly ameliorated by the compound. Furthermore, LPS-induced nuclear factor (NF)-κB DNA binding activity was drastically abolished by obovatol as shown by the electrophoretic mobility shift assay. The anti-neuroinflammation and anti-amyloidogenesis by obovatol were replicated in in vitro studies. These results show that obovatol mitigates LPS-induced amyloidogenesis and memory impairment via inhibiting NF-κB signal pathway, suggesting that the compound might be plausible therapeutic intervention for neuroinflammation-related diseases such as AD.
authors: College of Pharmacy and MRC, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors: Dong-Young
authors: DY
authors: Choi
authors: Jae Woong
authors: JW
authors: Lee
authors: Guihua
authors: G
authors: Lin
authors: Yong Kyung
authors: YK
authors: Lee
authors: Yeon Hee
authors: YH
authors: Lee
authors: Im Seop
authors: IS
authors: Choi
authors: Sang Bae
authors: SB
authors: Han
authors: Jae Kyung
authors: JK
authors: Jung
authors: Young Hee
authors: YH
authors: Kim
authors: Ki Ho
authors: KH
authors: Kim
authors: Ki-Wan
authors: KW
authors: Oh
authors: Jin Tae
authors: JT
authors: Hong
authors: Moon Soon
authors: MS
authors: Lee
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D031566:Magnolia / Q000737:chemistry; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010647:Phenyl Ethers / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D001713:Biphenyl Compounds; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010647:Phenyl Ethers; C036795:obovatol