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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.


Related in: MedlinePlus

GSPA administration reduced Aβ25–35-induced apoptosis. (A) Individual values (%) are listed in representative dot plots and living PC12 cells were gated as shown in the fluorescence-activated cell sorting histograms for control PC12 cells, PC12 cells exposed to 20 µM Aβ25–35, 20 µM Aβ25–35 + 50 µg/ml GSPA and 20 µM Aβ25–35 + 100 µg/ml GSPA. (B) A decrease in annexin-positive, PI-negative cells (lower right quadrant) and annexin-positive, PI-positive cells (higher right quadrant) was detected, which is indicative of reduced apoptosis. The increase in annexin-negative and PI-negative cells (lower left quadrant) is indicative of healthy non-apoptotic cells. Data are expressed as the mean ± standard error of the mean (n=3). *P<0.01, as compared with the control group; **P<0.01 and ***P<0.05, as compared with the Aβ25–35-treated group. GSPA, grape seed proanthocyanidin; Aβ25–35, amyloid β25–35 peptide, PI, propidium iodide; FITC, fluorescein isothiocyanate.
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f4-etm-0-0-3530: GSPA administration reduced Aβ25–35-induced apoptosis. (A) Individual values (%) are listed in representative dot plots and living PC12 cells were gated as shown in the fluorescence-activated cell sorting histograms for control PC12 cells, PC12 cells exposed to 20 µM Aβ25–35, 20 µM Aβ25–35 + 50 µg/ml GSPA and 20 µM Aβ25–35 + 100 µg/ml GSPA. (B) A decrease in annexin-positive, PI-negative cells (lower right quadrant) and annexin-positive, PI-positive cells (higher right quadrant) was detected, which is indicative of reduced apoptosis. The increase in annexin-negative and PI-negative cells (lower left quadrant) is indicative of healthy non-apoptotic cells. Data are expressed as the mean ± standard error of the mean (n=3). *P<0.01, as compared with the control group; **P<0.01 and ***P<0.05, as compared with the Aβ25–35-treated group. GSPA, grape seed proanthocyanidin; Aβ25–35, amyloid β25–35 peptide, PI, propidium iodide; FITC, fluorescein isothiocyanate.

Mentions: Annexin V-FITC and PI double staining can distinguish healthy cells (annexin-negative; PI-negative) from early apoptotic (annexin-positive; PI-negative), late apoptotic (annexin-positive; PI-positive), and necrotic (annexin-negative; PI-positive) cells (31). The apoptotic (early + late) rate of PC12 cells following Aβ25–35 treatment was 45.1%; however, GSPA pretreatment significantly reduced the apoptotic rate to 39.9% at 50 µg/ml (P<0.05) and 33.9% at 100 µg/ml (P<0.01). The healthy cell rate following Aβ25–35 treatment was 53.3%. However, GSPA pretreatment increased the healthy cell rate to 60% at 50 µg/ml and 65.1% at 100 µg/ml (both P<0.01, as compared with Aβ25–35 alone) (Fig. 4). The results suggest that GSPA reduces Aβ25–35-induced apoptosis.


Effects of grape seed proanthocyanidin on Alzheimer's disease in vitro and in vivo
GSPA administration reduced Aβ25–35-induced apoptosis. (A) Individual values (%) are listed in representative dot plots and living PC12 cells were gated as shown in the fluorescence-activated cell sorting histograms for control PC12 cells, PC12 cells exposed to 20 µM Aβ25–35, 20 µM Aβ25–35 + 50 µg/ml GSPA and 20 µM Aβ25–35 + 100 µg/ml GSPA. (B) A decrease in annexin-positive, PI-negative cells (lower right quadrant) and annexin-positive, PI-positive cells (higher right quadrant) was detected, which is indicative of reduced apoptosis. The increase in annexin-negative and PI-negative cells (lower left quadrant) is indicative of healthy non-apoptotic cells. Data are expressed as the mean ± standard error of the mean (n=3). *P<0.01, as compared with the control group; **P<0.01 and ***P<0.05, as compared with the Aβ25–35-treated group. GSPA, grape seed proanthocyanidin; Aβ25–35, amyloid β25–35 peptide, PI, propidium iodide; FITC, fluorescein isothiocyanate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4998082&req=5

f4-etm-0-0-3530: GSPA administration reduced Aβ25–35-induced apoptosis. (A) Individual values (%) are listed in representative dot plots and living PC12 cells were gated as shown in the fluorescence-activated cell sorting histograms for control PC12 cells, PC12 cells exposed to 20 µM Aβ25–35, 20 µM Aβ25–35 + 50 µg/ml GSPA and 20 µM Aβ25–35 + 100 µg/ml GSPA. (B) A decrease in annexin-positive, PI-negative cells (lower right quadrant) and annexin-positive, PI-positive cells (higher right quadrant) was detected, which is indicative of reduced apoptosis. The increase in annexin-negative and PI-negative cells (lower left quadrant) is indicative of healthy non-apoptotic cells. Data are expressed as the mean ± standard error of the mean (n=3). *P<0.01, as compared with the control group; **P<0.01 and ***P<0.05, as compared with the Aβ25–35-treated group. GSPA, grape seed proanthocyanidin; Aβ25–35, amyloid β25–35 peptide, PI, propidium iodide; FITC, fluorescein isothiocyanate.
Mentions: Annexin V-FITC and PI double staining can distinguish healthy cells (annexin-negative; PI-negative) from early apoptotic (annexin-positive; PI-negative), late apoptotic (annexin-positive; PI-positive), and necrotic (annexin-negative; PI-positive) cells (31). The apoptotic (early + late) rate of PC12 cells following Aβ25–35 treatment was 45.1%; however, GSPA pretreatment significantly reduced the apoptotic rate to 39.9% at 50 µg/ml (P<0.05) and 33.9% at 100 µg/ml (P<0.01). The healthy cell rate following Aβ25–35 treatment was 53.3%. However, GSPA pretreatment increased the healthy cell rate to 60% at 50 µg/ml and 65.1% at 100 µg/ml (both P<0.01, as compared with Aβ25–35 alone) (Fig. 4). The results suggest that GSPA reduces Aβ25–35-induced apoptosis.

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.


Related in: MedlinePlus