%0 Journal Article
%T 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
%A Young-Jung Lee
%A Dong-Young Choi
%A Im Seop Choi
%A Ki Ho Kim
%A Young Hee Kim
%A Hwan Mook Kim
%A Kiho Lee
%A Won Gil Cho
%A Jea Kyung Jung
%A Sang Bae Han
%A Jin-Yi Han
%A Sang-Yoon Nam
%A Young Won Yun
%A Jae Hwang Jeong
%A Ki-Wan Oh
%A Jin Tae Hong
%J Journal of Neuroinflammation
%D 2012
%I BioMed Central
%R 10.1186/1742-2094-9-35
%X 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 ¦Ìg/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 ¦ÌM).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 E2, tumor necrosis factor-¦Á, and interleukin-1¦Â in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-¦ÊB via inhibition of I¦ÊB 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 A¦Â1-42 generation, ¦Â- and ¦Ã-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.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.Alzheimer's disease (AD) is the most common cause of dementia accounting for 50% to 75% of all cases [1,2]. AD is pathologically characterized by the presence of senile plaq
%K Alzheimer's disease
%K Amyloid
%K Lipopolysaccharide
%K Neuroinflammation
%K 4-O-methylhonokiol
%K Magnolia officinalis
%K Memory impairment
%U http://www.jneuroinflammation.com/content/9/1/35