beta-Secretase (BACE1) inhibitors from pomegranate (Punica granatum) husk.
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.
Kwak
Hye-Min
HM
School of Applied Biosciences, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, Korea.
Jeon
So-Young
SY
Sohng
Bang-Ho
BH
Kim
Jong-Guk
JG
Lee
Jin-Man
JM
Lee
Kyung-Bok
KB
Jeong
Hyun-Hee
HH
Hur
Jong-Moon
JM
Kang
Young-Hwa
YH
Song
Kyung-Sik
KS
D000085:Acetates / Q000737:chemistry; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D000440:Butanols / Q000737:chemistry; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D029561:Lythraceae; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D013379:Substrate Specificity
D000085:Acetates; D000440:Butanols; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D004610:Ellagic Acid; C115642:punicalagin; C007650:ethyl acetate; D002392:Catechin; C045651:epigallocatechin gallate; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human