Biomol Ther.  2014 May;22(3):232-238.

Amelioration of Cognitive Dysfunction in APP/PS1 Double Transgenic Mice by Long-Term Treatment of 4-O-Methylhonokiol

Affiliations
  • 1College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea. jinthong@chungbuk.ac.kr
  • 2School of Equine industries, Cheju Halla University, Jeju 690-708, Republic of Korea.
  • 3College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea. dychoi@yu.ac.kr

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease without known ways to cure. A key neuropathologic manifestation of the disease is extracellular deposition of beta-amyloid peptide (Abeta). Specific mechanisms underlying the development of the disease have not yet been fully understood. In this study, we investigated effects of 4-O-methylhonokiol on memory dysfunction in APP/PS1 double transgenic mice. 4-O-methylhonokiol (1 mg/kg for 3 month) significantly reduced deficit in learning and memory of the transgenic mice, as determined by the Morris water maze test and step-through passive avoidance test. Our biochemical analysis suggested that 4-O-methylhonokiol ameliorated Abeta accumulation in the cortex and hippocampus via reduction in beta-site APP-cleaving enzyme 1 expression. In addition, 4-O-methylhonokiol attenuated lipid peroxidation and elevated glutathione peroxidase activity in the double transgenic mice brains. Thus, suppressive effects of 4-O-methylhonokiol on Abeta generation and oxidative stress in the brains of transgenic mice may be responsible for the enhancement in cognitive function. These results suggest that the natural compound has potential to intervene memory deficit and progressive neurodegeneration in AD patients.

Keyword

Alzheimer's disease; 4-O-methylhonokiol; APP/PS1 double transgenic; Antioxidant; Beta-site APP-cleaving enzyme

MeSH Terms

Alzheimer Disease
Animals
Brain
Glutathione Peroxidase
Hippocampus
Humans
Learning
Lipid Peroxidation
Maze Learning
Memory
Memory Disorders
Mice
Mice, Transgenic*
Neurodegenerative Diseases
Oxidative Stress
Glutathione Peroxidase
Maze Learning
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