earticle

영어

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 searchingfor 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 IC50 value of2.1×10−6 M and Ki value of 3.7×10−6 M. Both compounds exhibited less inhibition of α-secreatase (TACE) and other serineproteases including chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific and selective inhibitors toBACE1. Furthermore, both compounds significantly reduced the extracellular Aβ secretion in APP695-transfected B103 cells.