title: 4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase.
abstract: Oxidative stress induced neuronal cell death by accumulation of β-amyloid (Aβ) is a critical pathological mechanism of Alzheimer's disease (AD). Intracerebroventrical infusion of Aβ(1-42) (300 pmol/day per mouse) for 14 days induced neuronal cell death and memory impairment, but pre-treatment of 4-O-methylhonokiol (4-O-MH), a novel compound extracted from Magnolia officinalis for 3 weeks (0.2, 0.5 and 1.0 mg/kg) prior to the infusion of Aβ(1-42) and during the infusion dose dependently improved Aβ(1-42)-induced memory impairment and prevented neuronal cell death. Additionally, 4-O-MH reduced Aβ(1-42) infusion-induced oxidative damages of protein and lipid but reduced glutathione levels in the cortex and hippocampus. Aβ(1-42) infusion-induced activation of astrocytes and p38 mitogenic activated protein (MAP) kinase was also prevented by 4-O-MH in mice brains. In further study using culture cortical neurons, p38 MAP kinase inhibitor abolished the inhibitory effect of 4-O-MH (10 μM) on the Aβ(1-42) (5 μM)-induced reactive oxidative species generation and neuronal cell death. These results suggest that 4-O-MH might prevent the development and progression of AD through the reduction of oxidative stress and neuronal cell death via inactivation of p38 MAP kinase pathway.
authors.affiliation: College of Pharmacy and MRC, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Yong Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Im Seop
authors.initials: IS
authors.lastname: Choi
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ung Soo
authors.initials: US
authors.lastname: Lee
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D017705:Lignans / Q000494:pharmacology*; D015227:Lipid Peroxidation; D031566:Magnolia / Q000737:chemistry; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000009:adverse effects*; D050050:Protein Carbonylation; D017382:Reactive Oxygen Species / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: C542058:4-O-methylhonokiol; D016229:Amyloid beta-Peptides; D001713:Biphenyl Compounds; D017705:Lignans; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D048051:p38 Mitogen-Activated Protein Kinases