Beta-secretase (BACE1)-inhibiting stilbenoids from Smilax Rhizoma.
In the course of searching for BACE1 (beta-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of Smilax Rhizoma (the dried rhizomes of Smilax china L.) showed potent inhibitory activity. The active compounds were identified as a trans/cis-resveratrol mixture, oxyresveratrol, veraphenol, and cis-scirpusin A. They were shown to non-competitively inhibit BACE1 with the Ki values of 5.4 x 10(-6), 5.4 x 10(-6), 3.4 x 10(-6), and 5.4 x 10(-6)M and IC(50) values of 1.5 x 10(-5), 7.6 x 10(-6), 4.2 x 10(-6), and 1.0 x 10(-5)M, respectively. The active compounds were less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.
Jeon
S-Y
SY
Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University, 1370 Sankyuk-Dong, Daegu 702-701, Republic of Korea.
Kwon
S-H
SH
Seong
Y-H
YH
Bae
K
K
Hur
J-M
JM
Lee
Y-Y
YY
Suh
D-Y
DY
Song
K-S
KS
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D027343:Rhizome / Q000737:chemistry*; D032281:Smilax / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*
D013267:Stilbenes; D053829:Amyloid Precursor Protein Secretases