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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / prevention & control
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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Dose-Response Relationship, Drug
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Endopeptidases / metabolism*
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Gallic Acid / analogs & derivatives*
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Gallic Acid / isolation & purification
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Gallic Acid / pharmacology
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Glucosides / isolation & purification
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Glucosides / pharmacology*
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Humans
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Hydrolyzable Tannins / isolation & purification
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Hydrolyzable Tannins / pharmacology*
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In Vitro Techniques
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Inhibitory Concentration 50
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Kinetics
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Plant Extracts / chemistry
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Plant Extracts / pharmacology
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Protease Inhibitors / isolation & purification
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Protease Inhibitors / pharmacology*
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Sanguisorba* / chemistry
Substances
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Glucosides
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Hydrolyzable Tannins
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Plant Extracts
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Protease Inhibitors
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tellimagrandin II
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pentagalloylglucose
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Gallic Acid
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE1 protein, human