[논문]Suppression of β-Secretase (BACE1) Activity and β-Amyloid Protein-Induced Neurotoxicity by Solvent Fractions from Petasites japonicus Leaves

Hong, Seung-Young; Park, In-Shik; Jun, Mi-Ra

doi:10.3746/jfn.2011.16.1.018

Suppression of β-Secretase (BACE1) Activity and β-Amyloid Protein-Induced Neurotoxicity by Solvent Fractions from Petasites japonicus Leaves 원문보기

Journal of food science and nutrition, v.16 no.1, 2011년, pp.18 - 23

Hong, Seung-Young (Department of Food Science & Nutrition, Dong-A University) , Park, In-Shik (Department of Food Science & Nutrition, Dong-A University) , Jun, Mi-Ra (Department of Food Science & Nutrition, Dong-A University)

Abstract ▼ AI-Helper

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and extracellular senile plaques containing $\beta$-amyloid peptide (A$\beta$). The deposition of the A$\beta$ peptide following proteolytic processing of amyloid precursor protein (APP) by $\beta$-secretase (BACE1) and $\gamma$-secretase is a critical feature in the progression of AD. Among the plant extracts tested, the ethanol extract of Petasites japonicus leaves showed novel protective effect on B103 neuroblastoma cells against neurotoxicity induced by A$\beta$, as well as a strong suppressive effect on BACE1 activity. Ethanol extracts of P. japonicus leaves were sequentially extracted with methylene chloride, ethyl acetate and butanol and evaluated for potential to inhibit BACE1, as well as to suppress A$\beta$-induced neurotoxicity. Exposure to A$\beta$ significantly reduced cell viability and increased apoptotic cell death. However, pretreatment with ethyl acetate fraction of P. japonicus leaves prior to A$\beta$ (50 ${\mu}M$) significantly increased cell viability (p<0.01). In parallel, cell apoptosis triggered by A$\beta$ was also dramatically inhibited by ethyl acetate fraction of P. japonicus leaves. Moreover, the ethyl acetate fraction suppressed caspase-3 activity to the basal level at 30 ppm. Taken together, these results demonstrated that P. japonicus leaves appear to be a useful source for the inhibition and/or prevention of AD by suppression of BACE1 activity and attenuation of A$\beta$ induced neurocytotoxicity.

주제어

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제안 방법

For quantification of apoptotic cells, one hundred cells were assessed in each field at 200× magnification and ten randomized fields for each experimental condition were chosen.
One hundred cells were assessed in each field at 200× magnification and ten randomized fields for each experimental condition were chosen.

대상 데이터

All experiments were performed in triplicate. For each experiment, data are expressed as the mean±SE (n=3) and statistical significance was assessed by one-way analysis of variance (ANOVA) with unpaired Student’s t-tests.

데이터처리

For each experiment, data are expressed as the mean±SE (n=3) and statistical significance was assessed by one-way analysis of variance (ANOVA) with unpaired Student’s t-tests.
The values were compared to the positive control using analysis of variance (ANOVA) followed by unpaired Student’s t-tests.

이론/모형

Cell viability was determined by the conventional 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay (12). The assay depends primarily on mitochondrial metabolic capacity of viable cells and reflects the intracellular redox state (13).

성능/효과

Protective effect of solvent fractions from Petasites japonicus leaves on Aβ(25-35)-induced cell death. Data were shown as the percentage of MTT reduction, considering that the absorbance of control cells was 100%. Data (%) represent mean±SE of three independent experiments.
In conclusion, this study provides evidence that Aβ(25-35)-induced cellular injury was prevented by the solvent fractions of P. japonicas, with the ethyl acetate fraction of P. japonicus leaves exerting the strongest neuroprotective properties against BACE1 and Aβ-induced damage in B103 cells.
The results of this study suggest that the protective action of the solvent fractions of P. japonicus leaves against Aβ(25-35)-induced apoptotic death in B103 cells may, at least in part, be attributed in inhibition of the caspase cascade.

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