title: 4-O-methylhonokiol prevents memory impairment in the Tg2576 transgenic mice model of Alzheimer's disease via regulation of β-secretase activity.
abstract: Alzheimer's disease (AD), the most common form of dementia, is characterized by memory deficits and deposition of amyloid-β (Aβ) in the brain. It has been known that neuroinflammation and oxidative stress are critical factors in the development of AD. 4-O-methylhonokiol, an extract from Magnolia officinalis, is known to have anti-inflammatory and anti-oxidative effects. Thus, we investigated the properties of 4-O-methylhonokiol against progression and development of AD in Tg2576 mice. Tg2576 mice models show memory impairment and AD-like pathological features including Aβ deposition. Oral administration of 4-O-methylhonokiol through drinking water (1 mg/kg in 0.0002% Tween 80) for 12 weeks not only prevented memory impairment but also inhibited Aβ deposition. In addition, 4-O-methylhonokiol decreased β-secretase activity, oxidative lipid and protein damage levels, activation of astrocytes and microglia cells, and generation of IL-1β and TNF-α with increase of glutathione level in the brain. Our results showed that 4-O-methylhonokiol effectively prevented memory impairment by down-regulating β-secretase activity through inhibition of oxidative stress and neuroinflammatory responses in Tg2576 transgenic mice.
authors.affiliation: College of Pharmacy, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea.
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Choi
authors.forename: Yong Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Yoot Mo
authors.initials: YM
authors.lastname: Lee
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Sang-Yoon
authors.initials: SY
authors.lastname: Nam
authors.forename: Beom Jun
authors.initials: BJ
authors.lastname: Lee
authors.forename: Jong-Koo
authors.initials: JK
authors.lastname: Kang
authors.forename: Young Won
authors.initials: YW
authors.lastname: Yun
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 / Q000150:complications* / Q000235:genetics; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: C542058:4-O-methylhonokiol; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D017705:Lignans; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases; D005978:Glutathione