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Inhibitory Effects of Flavonoids Isolated from Leaves of Petasites japonicus on β-Secretase (BACE1)
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논문 기본 정보

Type
Academic journal
Author
Kyung-Sik Song (경북대학교) Sun-Ha Choi (경북대학교) Jong-Moon Hur (경북대학교) Hyo-Jun Park (경북대학교) Eun-Ju Yang (경북대학교) Inhee Mook-Jung (서울대학교) Jung-Hyun Yi (동아대학교) Mira Jun (동아대학교)
Journal
Korean Society of Food Science and Technology Food Science and Biotechnology Vol. 17 No.6 KCI Accredited Journals SCIE
Published
2008.12
Pages
1,165 - 1,170 (6page)

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Inhibitory Effects of Flavonoids Isolated from Leaves of Petasites japonicus on β-Secretase (BACE1)
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The deposition of the amyloid β (Aβ)-peptide following proteolytic processing of amyloid precursor protein (APP) by β-secretase (BACE1) and γ-secretase is critical feature in the progress of Alzheimer’s disease (AD). Consequently, BACE1, a key enzyme in the production of Aβ, is a prime target for therapeutic intervention in AD. In the course of searching for BACE1 inhibitors from natural sources, the ethyl acetate fraction of Petasites japonicus showed potent inhibitory activity. Two BACE1 inhibitors quercetin (QC) and kaempferol 3-O-(6''-acetyl)-β-glucopyranoside (KAG) were isolated from P. japonicus by activity-guided purification. QC, in particular, non-competitively attenuated BACE1 activity with IC?? value of 2.1×10?? M and K<SUB>i</SUB> value of 3.7×10?? M. Both compounds exhibited less inhibition of α-secreatase (TACE) and other serine proteases including chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific and selective inhibitors to BACE1. Furthermore, both compounds significantly reduced the extracellular Aβ secretion in APP???-transfected B103 cells.
#Alzheimer's disease #β-amyloid peptide #flavonoid #Petasites japonicus #β-secretase

Contents

Abstract
Introduction
Materials and Methods
Results and Discussion
Acknowledgments
References

References (35)

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Glenner GG / 1984 / Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein / Biochem. Bioph. Res. Co 120:885~890 google schola Citron M / 2004 / Strategies for disease modification in Alzheimer’s disease / Nat. Rev. Neurosci 5:677~685 google schola Jucker M / 2006 / In Alzheimer: 100 years and Beyond / Springer google schola Selkoe DJ / 1994 / Normal and abnormal biology of the β-amyloid precursor protein / Annu. Rev. Neurosci 17:489~517 google schola Vassar R / 1999 / Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE / Science 286:735~741 google schola

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