4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase.
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.
Lee
Yong Kyung
YK
College of Pharmacy and MRC, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk 361-763, South Korea.
Choi
Im Seop
IS
Ban
Jung Ok
JO
Lee
Hwa Jeong
HJ
Lee
Ung Soo
US
Han
Sang Bae
SB
Jung
Jae Kyung
JK
Kim
Young Hee
YH
Kim
Ki Ho
KH
Oh
Ki-Wan
KW
Hong
Jin Tae
JT
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*
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