Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation,amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

Background: 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 1-42generation,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. © 2012 lee et al; licensee biomed central ltd.