Abstract
In the course of screening for anti-dementia agents from natural products, two beta-secretase (BACE1) inhibitors were isolated from the husk of pomegranate (Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with IC50 values of 3.9 x10(-6) and 4.1x10(-7) M and Ki values of 2.4x10(-5) and 5.9x10(-7) M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating 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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Acetates / chemistry
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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Butanols / chemistry
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Catechin / analogs & derivatives
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Catechin / pharmacology
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Dose-Response Relationship, Drug
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Ellagic Acid / chemistry
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Ellagic Acid / isolation & purification
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Ellagic Acid / pharmacology
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Endopeptidases / metabolism*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / isolation & purification*
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Enzyme Inhibitors / pharmacology
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Fruit / chemistry*
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Humans
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Hydrolyzable Tannins / chemistry
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Hydrolyzable Tannins / isolation & purification
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Hydrolyzable Tannins / pharmacology
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Lythraceae*
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Plant Extracts / chemistry
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology
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Plants, Medicinal / chemistry
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Substrate Specificity
Substances
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Acetates
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Butanols
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Enzyme Inhibitors
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Hydrolyzable Tannins
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Plant Extracts
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Ellagic Acid
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punicalagin
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ethyl acetate
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Catechin
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epigallocatechin gallate
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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