Nutr Res Pract.  2015 Oct;9(5):480-488. 10.4162/nrp.2015.9.5.480.

Protective role of caffeic acid in an Abeta25-35-induced Alzheimer's disease model

• Kim JH
• Wang Q
• Choi JM
• Lee S
• Cho EJ

• KMID: 2313868
• DOI: http://doi.org/10.4162/nrp.2015.9.5.480

Abstract

BACKGROUND/OBJECTIVES
Alzheimer's disease (AD) is characterized by deficits in memory and cognitive functions. The accumulation of amyloid beta peptide (Abeta) and oxidative stress in the brain are the most common causes of AD.
MATERIALS/METHODS
Caffeic acid (CA) is an active phenolic compound that has a variety of pharmacological actions. We studied the protective abilities of CA in an Abeta25-35-injected AD mouse model. CA was administered at an oral dose of 10 or 50 mg/kg/day for 2 weeks. Behavioral tests including T-maze, object recognition, and Morris water maze were carried out to assess cognitive abilities. In addition, lipid peroxidation and nitric oxide (NO) production in the brain were measured to investigate the protective effect of CA in oxidative stress.
RESULTS
In the T-maze and object recognition tests, novel route awareness and novel object recognition were improved by oral administration of CA compared with the Abeta25-35-injected control group. These results indicate that administration of CA improved spatial cognitive and memory functions. The Morris water maze test showed that memory function was enhanced by administration of CA. In addition, CA inhibited lipid peroxidation and NO formation in the liver, kidney, and brain compared with the Abeta25-35-injected control group. In particular, CA 50 mg/kg/day showed the stronger protective effect from cognitive impairment than CA 10 mg/kg/day.
CONCLUSIONS
The present results suggest that CA improves Abeta25-35-induced memory deficits and cognitive impairment through inhibition of lipid peroxidation and NO production.

Keyword

Caffeic acid; Alzheimer's disease; amyloid beta; oxidative stress; nitric oxide

MeSH Terms

Administration, Oral
Alzheimer Disease*
Amyloid beta-Peptides
Animals
Brain
Kidney
Lipid Peroxidation
Liver
Memory
Memory Disorders
Mice
Nitric Oxide
Oxidative Stress
Phenol
Water
Amyloid beta-Peptides
Nitric Oxide
Phenol
Water

Figure

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  Fig. 1 Behavioral experimental schedule for mice injected with Aβ25-35.

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  Fig. 2 Spatial alternation test in the T-maze test. Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~bThe different letters among groups represent significant differences (P < 0.05) by Duncan's multiple range test. * The space perceptive abilities for old and new routes are significantly different as determined by Student's t-test (P < 0.05).

• 

  Fig. 3 Effect of CA on objective recognition test. Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~cThe different letters among groups represent significant differences (P < 0.05) by Duncan's multiple range test. * The object cognitive abilities for original and novel objects are significantly different as determined by Student's t-test (P < 0.05).

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  Fig. 4 Effect of CA on spatial learning and memory impairment after injection of Aβ25-35 in the Morris water maze test. Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~bThe different letters represent significant differences (P < 0.05) by Duncan's multiple range test.

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  Fig. 5 Effect of CA on memory impairment induced by injection of Aβ25-35 in the Morris water maze test. Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~bThe different letters represent significant differences (P < 0.05) by Duncan's multiple range test.

• 

  Fig. 6 Effects of CA on the performance of Aβ25-35 treated mice in finding the hidden (A) and exposed (B) platforms in the Morris water maze test. Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~bThe different letters represent significant differences (P < 0.05) by Duncan's multiple range test.

• 

  Fig. 7 Effect of CA administration on lipid peroxidation in mouse brain (A), kidney (B), and liver (C). Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~dThe different letters represent significant differences (P < 0.05) by Duncan's multiple range test.

• 

  Fig. 8 Effect of CA administration on Aβ25-35 induced NO production in mouse brain (A), kidney (B), and liver (C). Normal = 0.9% NaCl injection + oral administration of water; Control = Aβ25-35 injection + oral administration of water; CA10 = Aβ25-35 injection + oral administration of CA (10 mg/kg/day); CA50 = Aβ25-35 injection + oral administration of CA (50 mg/kg/day). Values are mean ± SD. a~dThe different letters represent significant differences (P < 0.05) by Duncan's multiple range test.

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