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: Yong Kyung Lee, Im Seop Choi, Jung Ok Ban, Hwa Jeong Lee, Ung Soo Lee, Sang Bae Han, Jae Kyung Jung, Young Hee Kim, Ki Ho Kim, Ki-Wan Oh, Jin Tae Hong
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 22 Issue 5 Pg. 476-86 (May 2011) ISSN: 1873-4847 [Electronic] United States
• PMID: 20688501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 4-O-methylhonokiol
• Amyloid beta-Peptides
• Biphenyl Compounds
• Lignans
• Peptide Fragments
• Reactive Oxygen Species
• amyloid beta-protein (1-42)
• p38 Mitogen-Activated Protein Kinases

Topics

• Alzheimer Disease (physiopathology)
• Amyloid beta-Peptides (adverse effects)
• Analysis of Variance
• Animals
• Apoptosis
• Astrocytes (drug effects, metabolism)
• Biphenyl Compounds (pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Hippocampus (drug effects, pathology)
• Lignans (pharmacology)
• Lipid Peroxidation
• Magnolia (chemistry)
• Male
• Memory Disorders (chemically induced, drug therapy, physiopathology)
• Mice
• Mice, Inbred ICR
• Neurons (cytology, metabolism)
• Oxidative Stress
• Peptide Fragments (adverse effects)
• Protein Carbonylation
• Reactive Oxygen Species (analysis)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)