In:
Journal of Neuroinflammation, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2012-12)
Abstract:
Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairments. In the present study, we investigated the possible preventive effects of 4- O -methylhonokiol, a constituent of Magnolia officinalis , on memory deficiency caused by LPS, along with the underlying mechanisms. Methods We investigated whether 4- O -methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) prevents memory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4- O -methylhonkiol (0.5, 1 and 2 μM). Results Oral administration of 4- O -methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4- O -methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4- O -methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E 2 , tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4- O -methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effect on neuroinflammation, 4- O -methylhonokiol inhibited LPS-induced Aβ 1-42 generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells. Conclusion These results suggest that 4- O -methylhonokiol inhibits LPS-induced amyloidogenesis via anti-inflammatory mechanisms. Thus, 4- O -methylhonokiol can be a useful agent against neuroinflammation-associated development or the progression of AD.
Type of Medium:
Online Resource
ISSN:
1742-2094
DOI:
10.1186/1742-2094-9-35
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2012
detail.hit.zdb_id:
2156455-3
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