Nutr Res Pract.  2022 Apr;16(2):173-193. 10.4162/nrp.2022.16.2.173.

Protective effects of Populus tomentiglandulosa against cognitive impairment by regulating oxidative stress in an amyloid beta_25–35 -induced Alzheimer's disease mouse model

• Kwon YR
• Kim JH
• Lee S
• Kim HY
• Cho EJ

• KMID: 2527809
• DOI: http://doi.org/10.4162/nrp.2022.16.2.173

Abstract

BACKGROUND/OBJECTIVES
Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of Populus tomentiglandulosa (PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD.
MATERIALS/METHODS
We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ _25–35-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues.
RESULTS
PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity. Furthermore, administration of PT significantly inhibited the production of lipid peroxide, NO, and ROS in the brain, liver, and kidney, suggesting that PT protected against oxidative stress.
CONCLUSIONS
Our study demonstrated that administration of PT improved Aβ_25–35 -induced cognitive impairment by regulating oxidative stress. Therefore, we propose that PT could be used as a natural agent for AD improvement.

Keyword

Populus; cognitive dysfunction; oxidative stress; amyloid; neurodegenerative diseases

Figure

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  Fig. 1 The experimental schedule in Aβ25-35-induced Alzheimer's disease mouse model.Aβ, amyloid beta; PT, Populus tomentiglandulosa.

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  Fig. 2 HPLC chromatogram of ethyl acetate fraction from Populus tomentiglandulosa and salicin.

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  Fig. 3 Effect of EtOAc fraction from PT on space perceptive ability in the T-maze test.The results are expressed as the mean ± SD. The asterisk (*) indicates that the space perceptive abilities for old and new routes were significantly different, as determined by Student's t-test (P < 0.05). Different letters (a, b) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). Normal = 0.9% NaCl i.c.v. injection + drinking water; Control = Aβ25-35 i.c.v. injection (25 nM/5 μL) + drinking water; PT50 = Aβ25-35 i.c.v. injection (25 nM/5 μL) + oral administration of the EtOAc fraction from PT (50 mg/kg/day); PT100 = Aβ25-35 i.c.v. injection (25 nM/5 μL) + oral administration of the EtOAc fraction from PT (100 mg/kg/day); DO = Aβ25-35 i.c.v. injection (25 nM/5 μL) + oral administration of donepezil (5 mg/kg/day).PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta; EtOAc, ethyl acetate.

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  Fig. 4 Effect of ethyl acetate fraction from PT on objective cognitive ability in novel object recognition test.The results are expressed as mean ± SD. The asterisk (*) indicates that the object cognitive abilities for familiar and novel routes are significantly different, as determined by Student's t-test (P < 0.05). Different letters (a–c) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

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  Fig. 5 Effect of ethyl acetate fraction from PT on representative tracking pathway (A) and escape latency (B) in the Morris water-maze test.The results are expressed as mean ± SD. Different letters (a, b) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil.

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  Fig. 6 Effect of ethyl acetate fraction from PT on the percent of time stayed in the target quadrant in Morris water-maze test.The results are expressed as mean ± SD. Different letters (a, b) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

• 

  Fig. 7 Effect of ethyl acetate fraction from PT on escape latency to hidden platform (A) and the exposed platform (B) in the Morris water-maze test.The results are expressed as mean ± SD. Different letters (a, b) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test. NS indicates no significant differences among groups (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

• 

  Fig. 8 Effects of ethyl acetate fraction from PT on AST (A) and ALT (B) in Aβ25-35-induced mice.The results are expressed as mean ± SD. NS indicates no significant differences among groups (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.AST, aspartate aminotransferase; PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta; ALT, alanine aminotransferase.

• 

  Fig. 9 Effect of ethyl acetate fraction from PT on lipid peroxidation in brain (A), liver (B), and kidney (C) in Aβ25-35-induced mice.The data are expressed as mean ± SD. Different letters (a–d) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.MDA, malondialdehyde; PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

• 

  Fig. 10 Effect of ethyl acetate fraction from PT on NO generation in brain (A), liver (B), and kidney (C) in Aβ25-35-induced mice.The results are expressed as mean ± SD. Different letters (a–c) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

• 

  Fig. 11 Effect of ethyl acetate fraction from PT on reactive oxygen species production in the brain (A), liver (B), and kidney (C) of Aβ25-35-induced mice.The results are expressed as mean ± SD. Different letters (a–d) among groups indicate significant differences (P < 0.05) by Duncan's multiple range test (n = 7). The mice were grouped and treated as described in Fig. 3.PT, Populus tomentiglandulosa; DO, donepezil; Aβ, amyloid beta.

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