Obovatol attenuates LPS-induced memory impairments in mice via inhibition of NF-¦ÊB signaling pathway

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• 作者：Dong-Young Choi^a ; ^{neochallenger@yahoo.co.kr} ; Jae Woong Lee^a ; ^{2jaewoong@hanmail.net} ; Guihua Lin^a ; ^{linguihua@sohu.com} ; Yong Kyung Lee^a ; ^{kurt07@hanmail.net} ; Yeon Hee Lee^a ; ^{yhvet@kfda.go.kr} ; Im Seop Choi^a ; ^{aassa33@naver.com} ; Sang Bae Han^a ; ^{shan@chungbuk.ac.kr} ; Jae Kyung Jung^a ; ^{orgjkjung@chungbuk.ac.kr} ; Young Hee Kim^c ; ^{yhkim1st@biolandkorea.com} ; Ki Ho Kim^c ; ^{kiholee@biolandkorea.com} ; Ki-Wan Oh^a ; ^{kiwan@chungbuk.ac.kr} ; Jin Tae Hong^a ; ^{jinthong@chungbuk.ac.kr} ; Moon Soon Lee^b ; ^{mslee416@chungbuk.ac.kr}
• 关键词：A¦Â ; ¦Â-amyloid ; AD ; Alzheimer&rsquo ; s disease ; LPS ; lipopolysaccharide ; APP ; amyloid precursor protein ; BACE ; beta-site APP-cleaving enzyme ; COX ; cyclooxygenase ; NSAIDs ; non-steroidal anti-inflammatory drugs ; NOS ; nitric oxide synthase ; NF-¦ÊB ; nuclear f
• 刊名：Neurochemistry International
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：60
• 期：1
• 页码：68-77
• 全文大小：1196 K

文摘

Neuroinflammation and accumulation of ¦Â-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 ¦Â-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 A¦Â_1-42 formation, ¦Â- and ¦Ã-secretases activities and levels of amyloid precursor protein, neuronal ¦Â-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)-¦ÊB 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-¦ÊB signal pathway, suggesting that the compound might be plausible therapeutic intervention for neuroinflammation-related diseases such as AD.