Beta-secretase (BACE1) inhibitors from Sanguisorbae Radix.
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.
Lee
Hee-Ju
HJ
School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, 1370 Sankyuk-Dong, Daegu 702-701, Korea.
Seong
Yeon-Hee
YH
Bae
Ki-Hwan
KH
Kwon
Soon-Ho
SH
Kwak
Hye-Min
HM
Nho
Si-Kab
SK
Kim
Kyung-A
KA
Hur
Jong-Moon
JM
Lee
Kyung Bok
KB
Kang
Young-Hwa
YH
Song
Kyung-Sik
KS
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
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