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Effects of grape seed proanthocyanidin on Alzheimer's disease in vitro and in vivo

View Article: PubMed Central - PubMed

ABSTRACT

Grape seed proanthocyanidin (GSPA) consists of catechin, epicatechin and epicatechin gallate, which are strong antioxidants that are beneficial to health and may attenuate or prevent Alzheimer's disease (AD). In the present study, the effects of GSPA on pheochromocytoma (PC12) cell viability were determined using cell counting kit-8 and lactate dehydrogenase (LDH) assays, whereas apoptosis and mitochondrial membrane potential (Ψm) were measured via flow cytometry analysis. The effect of GSPA administration on the behavior and memory of amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mice was assessed using a Morris water maze. APP Aβ peptides and tau hyperphosphorylation were examined by western blotting; whereas the expression levels of PS-1 were evaluated by reverse transcription-quantitative polymerase chain reaction and compared with pathological sections stained with hematoxylin-eosin and Congo red. Data from the in vitro experiments demonstrated that GSPA significantly alleviated Aβ25–35 cytotoxicity and LDH leakage ratio, inhibited apoptosis and increased Ψm. The findings from the in vivo experiments showed a significant enhancement in cognition and spatial memory ability, an improvement in the pathology of APP and tau protein and a decrease in PS-1 mRNA expression levels. Therefore, the results of the present study indicated that GSPA may be a novel therapeutic strategy for the treatment of AD or may, at the very least, improve the quality of life of patients with AD.

No MeSH data available.


(A) Western blot analysis of APP and Tau protein among the control, APP/PS1 model, APP/PS1 plus donepezil and APP/PS1 plus low (50 mg/kg/day) and high (100 mg/kg/day) dose GSPA groups, respectively. (B) Quantitative comparison of the protein levels of APP and Tau among the group, relative to β-actin. Data are expressed as the mean ± standard error of the mean (n=6) mice. #P<0.05 and ##P<0.01, as compared with the control group; *P<0.05 and **P<0.01, as compared with the APP/PS1 model group.
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f9-etm-0-0-3530: (A) Western blot analysis of APP and Tau protein among the control, APP/PS1 model, APP/PS1 plus donepezil and APP/PS1 plus low (50 mg/kg/day) and high (100 mg/kg/day) dose GSPA groups, respectively. (B) Quantitative comparison of the protein levels of APP and Tau among the group, relative to β-actin. Data are expressed as the mean ± standard error of the mean (n=6) mice. #P<0.05 and ##P<0.01, as compared with the control group; *P<0.05 and **P<0.01, as compared with the APP/PS1 model group.

Mentions: Western blot analyses of APP and tau protein expression levels are shown in Fig. 9. Low APP and tau protein expression levels were detected in the control group. Significantly increased APP and tau protein expression levels were detected in the hippocampi of mice in the APP/PS1 model group (P<0.05 and P<0.01, respectively). Treatment with oral donepezil hydrochloride for 2 months significantly decreased APP and tau protein expression levels in the hippocampi of the APP/PS1 donepezil group, as compared with the APP/PS1 model group (P<0.01 and P<0.05, respectively). Furthermore, 2-month administration of oral GSPA significantly decreased APP and tau protein expression levels in the hippocampi of mice in the APP/PS1-treated high dose group, as compared with the APP/PS1 model group (P<0.05). The results suggest that GSPA is able to decrease APP and Tau protein expression levels in the hippocampi of APP/PS1 double transgenic mice.


Effects of grape seed proanthocyanidin on Alzheimer's disease in vitro and in vivo
(A) Western blot analysis of APP and Tau protein among the control, APP/PS1 model, APP/PS1 plus donepezil and APP/PS1 plus low (50 mg/kg/day) and high (100 mg/kg/day) dose GSPA groups, respectively. (B) Quantitative comparison of the protein levels of APP and Tau among the group, relative to β-actin. Data are expressed as the mean ± standard error of the mean (n=6) mice. #P<0.05 and ##P<0.01, as compared with the control group; *P<0.05 and **P<0.01, as compared with the APP/PS1 model group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998082&req=5

f9-etm-0-0-3530: (A) Western blot analysis of APP and Tau protein among the control, APP/PS1 model, APP/PS1 plus donepezil and APP/PS1 plus low (50 mg/kg/day) and high (100 mg/kg/day) dose GSPA groups, respectively. (B) Quantitative comparison of the protein levels of APP and Tau among the group, relative to β-actin. Data are expressed as the mean ± standard error of the mean (n=6) mice. #P<0.05 and ##P<0.01, as compared with the control group; *P<0.05 and **P<0.01, as compared with the APP/PS1 model group.
Mentions: Western blot analyses of APP and tau protein expression levels are shown in Fig. 9. Low APP and tau protein expression levels were detected in the control group. Significantly increased APP and tau protein expression levels were detected in the hippocampi of mice in the APP/PS1 model group (P<0.05 and P<0.01, respectively). Treatment with oral donepezil hydrochloride for 2 months significantly decreased APP and tau protein expression levels in the hippocampi of the APP/PS1 donepezil group, as compared with the APP/PS1 model group (P<0.01 and P<0.05, respectively). Furthermore, 2-month administration of oral GSPA significantly decreased APP and tau protein expression levels in the hippocampi of mice in the APP/PS1-treated high dose group, as compared with the APP/PS1 model group (P<0.05). The results suggest that GSPA is able to decrease APP and Tau protein expression levels in the hippocampi of APP/PS1 double transgenic mice.

View Article: PubMed Central - PubMed

ABSTRACT

Grape seed proanthocyanidin (GSPA) consists of catechin, epicatechin and epicatechin gallate, which are strong antioxidants that are beneficial to health and may attenuate or prevent Alzheimer's disease (AD). In the present study, the effects of GSPA on pheochromocytoma (PC12) cell viability were determined using cell counting kit-8 and lactate dehydrogenase (LDH) assays, whereas apoptosis and mitochondrial membrane potential (&Psi;m) were measured via flow cytometry analysis. The effect of GSPA administration on the behavior and memory of amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mice was assessed using a Morris water maze. APP A&beta; peptides and tau hyperphosphorylation were examined by western blotting; whereas the expression levels of PS-1 were evaluated by reverse transcription-quantitative polymerase chain reaction and compared with pathological sections stained with hematoxylin-eosin and Congo red. Data from the in vitro experiments demonstrated that GSPA significantly alleviated A&beta;25&ndash;35 cytotoxicity and LDH leakage ratio, inhibited apoptosis and increased &Psi;m. The findings from the in vivo experiments showed a significant enhancement in cognition and spatial memory ability, an improvement in the pathology of APP and tau protein and a decrease in PS-1 mRNA expression levels. Therefore, the results of the present study indicated that GSPA may be a novel therapeutic strategy for the treatment of AD or may, at the very least, improve the quality of life of patients with AD.

No MeSH data available.