Beta-secretase (BACE1) inhibitors from Perilla frutescens var. acuta.
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.
Choi
Sun-Ha
SH
Division of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 702-701, Korea.
Hur
Jong-Moon
JM
Yang
Eun-Ju
EJ
Jun
Mira
M
Park
Hyo-Jun
HJ
Lee
Kyung-Bok
KB
Moon
Eunho
E
Song
Kyung-Sik
KS
D000110:Acetylcholinesterase / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D002918:Chymotrypsin / Q000378:metabolism; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology; D053630:Depsides / Q000302:isolation & purification / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D047311:Luteolin / Q000302:isolation & purification / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D031344:Perilla frutescens / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology; D000097123:Rosmarinic Acid
D000110:Acetylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D002800:Cholinesterase Inhibitors; D002918:Chymotrypsin; D002934:Cinnamates; D053630:Depsides; D047311:Luteolin; D010196:Pancreatic Elastase; D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D000097123:Rosmarinic Acid; C509280:BACE1 protein, human