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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.
J Neuroinflammation. 2012 Feb 19; 9:35.JN

Abstract

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 E2, 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 Aβ1-42 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.

Authors+Show Affiliations

College of Pharmacy, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22339795

Citation

Lee, Young-Jung, et al. "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." Journal of Neuroinflammation, vol. 9, 2012, p. 35.
Lee YJ, Choi DY, Choi IS, et al. 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. J Neuroinflammation. 2012;9:35.
Lee, Y. J., Choi, D. Y., Choi, I. S., Kim, K. H., Kim, Y. H., Kim, H. M., Lee, K., Cho, W. G., Jung, J. K., Han, S. B., Han, J. Y., Nam, S. Y., Yun, Y. W., Jeong, J. H., Oh, K. W., & Hong, J. T. (2012). 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. Journal of Neuroinflammation, 9, 35. https://doi.org/10.1186/1742-2094-9-35
Lee YJ, et al. 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. J Neuroinflammation. 2012 Feb 19;9:35. PubMed PMID: 22339795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lee,Young-Jung, AU - Choi,Dong-Young, AU - Choi,Im Seop, AU - Kim,Ki Ho, AU - Kim,Young Hee, AU - Kim,Hwan Mook, AU - Lee,Kiho, AU - Cho,Won Gil, AU - Jung,Jea Kyung, AU - Han,Sang Bae, AU - Han,Jin-Yi, AU - Nam,Sang-Yoon, AU - Yun,Young Won, AU - Jeong,Jae Hwang, AU - Oh,Ki-Wan, AU - Hong,Jin Tae, Y1 - 2012/02/19/ PY - 2011/10/07/received PY - 2012/02/19/accepted PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/8/15/medline SP - 35 EP - 35 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 9 N2 - 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 E2, 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 Aβ1-42 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/22339795/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_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-9-35 DB - PRIME DP - Unbound Medicine ER -