کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2200893 | 1099984 | 2012 | 10 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Obovatol attenuates LPS-induced memory impairments in mice via inhibition of NF-κB signaling pathway Obovatol attenuates LPS-induced memory impairments in mice via inhibition of NF-κB signaling pathway](/preview/png/2200893.png)
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.
► Obovatol attenuates cognitive impairments in systemic LPS-injected mice.
► The preventative effects might be related to anti-amyloidogenic and anti-neuroinflammatory properties of obovatol.
► Inhibition of NF-kappaB signaling may confer the beneficial effects.
Journal: Neurochemistry International - Volume 60, Issue 1, January 2012, Pages 68–77