Abstract
In the course of screening for anti-dementia agents from natural products, two beta-secretase (BACE1) inhibitors were isolated from the methanolic extract of Perilla frutescens var. acuta and identified as luteolin (1) and rosmarinic acid (2) with IC50 values of 5.0 x 10(-7) M and 2.1 x 10(-5) M, respectively. They inhibited BACE1 in a non-competitive manner with a substrate in Dixon plots, suggesting that they might bind to either beta-secretase subsite or to another regulatory site. Kivalues of 1 and 2 were 6.2 x 10(-5) M and 3.9 x 10(-5) M, respectively. They were less inhibitory against other enzymes such as alpha-secretase (TACE), acetylcholine esterase (AchE), chymotrypsin, and elastase, indicating that they were relatively specific inhibitors of BACE1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / metabolism
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Cholinesterase Inhibitors / pharmacology
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Chromatography, Thin Layer
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Chymotrypsin / metabolism
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Cinnamates / isolation & purification
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Cinnamates / pharmacology
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Depsides / isolation & purification
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Depsides / pharmacology
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Enzyme-Linked Immunosorbent Assay
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Humans
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Luteolin / isolation & purification
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Luteolin / pharmacology
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Pancreatic Elastase / antagonists & inhibitors
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Perilla frutescens / chemistry*
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Plant Leaves / chemistry
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Recombinant Proteins / chemistry
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Rosmarinic Acid
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Serine Proteinase Inhibitors / isolation & purification*
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Serine Proteinase Inhibitors / pharmacology*
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Trypsin Inhibitors / pharmacology
Substances
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Cholinesterase Inhibitors
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Cinnamates
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Depsides
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Recombinant Proteins
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Serine Proteinase Inhibitors
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Trypsin Inhibitors
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Acetylcholinesterase
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Amyloid Precursor Protein Secretases
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Chymotrypsin
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Pancreatic Elastase
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Aspartic Acid Endopeptidases
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BACE1 protein, human
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Luteolin