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: Young-Jung Lee, Dong-Young Choi, Yong Kyoung Lee, Yoot Mo Lee, Sang Bae Han, Young Hee Kim, Ki Ho Kim, Sang-Yoon Nam, Beom Jun Lee, Jong-Koo Kang, Young Won Yun, Ki-Wan Oh, Jin Tae Hong
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 29 Issue 3 Pg. 677-90 ( 2012) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 22330831 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-O-methylhonokiol
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Anti-Inflammatory Agents
• Biphenyl Compounds
• Lignans
• Peptide Fragments
• amyloid beta-protein (1-40)
• amyloid beta-protein (1-42)
• Amyloid Precursor Protein Secretases
• Glutathione

Topics

• Alzheimer Disease (complications, genetics)
• Amyloid Precursor Protein Secretases (metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Analysis of Variance
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Avoidance Learning (drug effects)
• Biphenyl Compounds (therapeutic use)
• Brain (drug effects, pathology)
• Disease Models, Animal
• Exploratory Behavior (drug effects)
• Gene Expression Regulation (drug effects, genetics)
• Glutathione (metabolism)
• Humans
• Lignans (therapeutic use)
• Lipid Peroxidation (drug effects)
• Maze Learning (drug effects)
• Memory Disorders (etiology, genetics, pathology, prevention & control)
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Oxidative Stress (drug effects, genetics)
• Peptide Fragments (metabolism)
• Protein Carbonylation (drug effects, genetics)
• Time Factors