title: Beta-secretase (BACE1) inhibitors from Sanguisorbae Radix.
abstract: In the course of screening anti-dementia agents from natural products, two beta-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-beta-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-beta-D-glucopyranoside (2) and were shown to non-competitively inhibit beta-secretase (BACE1) with the IC50 values of 3.10x10(-6) M and 3.76x10(-6) M, respectively. The Ki values of 1 and 2 were 6.84x10(-6) M and 5.13x10(-6) M. They were less inhibitory to alphasecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.
authors.affiliation: School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, 1370 Sankyuk-Dong, Daegu 702-701, Korea.
authors.forename: Hee-Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Seong
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Bae
authors.forename: Soon-Ho
authors.initials: SH
authors.lastname: Kwon
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Kwak
authors.forename: Si-Kab
authors.initials: SK
authors.lastname: Nho
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Kim
authors.forename: Jong-Moon
authors.initials: JM
authors.lastname: Hur
authors.forename: Kyung Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Kang
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Song
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D031993:Sanguisorba / Q000737:chemistry
chemical_list: D005960:Glucosides; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D011480:Protease Inhibitors; C473299:tellimagrandin II; C435084:pentagalloylglucose; D005707:Gallic Acid; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human