Selective cholinesterase inhibitory activities of a new monoterpene diglycoside and other constituents from Nelumbo nucifera stamens.
A new beta-cyclogeraniol diglycoside (5), along with four known components, cycloartenol (1), p-hydroxybenzoic acid (2), vanilloloside (3), and 5'-O-methyladenosine (4), were first isolated from the n-BuOH fraction of Nelumbo nucifera stamens. The chemical structure of 5 was elucidated as 1-hydroxymethyl-2,6,6-trimethyl-1-cyclohexene 9-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (nuciferoside) on the basis of chemical and spectroscopic evidence, including 1D, 2D NMR, and MS. The anti-Alzheimer effects of 1-5 were evaluated via the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) inhibition assays. Compounds 1-3 and 5 showed good and noncompetitive inhibition against AChE with IC(50) values of 11.89, 20.07, 4.55, and 3.20 microM and K(i)values of 15.71, 25.44, 7.76, and 5.76 microM, respectively. Compounds 1, 2, and 5 also possessed BChE inhibitory activities with IC(50) values of 13.93, 62.29, 205.78, and 83.06 microM, respectively. The selectivity index (SI) values of 1, 2, 3, and 5, calculated from IC(50) values of BChE and AChE, were 1.2, 3.1, 45.7, and 26.0. However, all isolated compounds lacked BACE1 inhibition up to 100 microM. Therefore, N. nucifera stamens-derived compounds could potentially exert their primary anti-Alzheimer effects as AChE inhibitors rather than BACE1 inhibitors.
Jung
Hyun Ah
HA
Division of Food Science and Biotechnology, Pukyong National University, Busan 608-737, Republic of Korea.
Jung
Yu Jung
YJ
Hyun
Sook Kyung
SK
Min
Byung-Sun
BS
Kim
Dong-Wook
DW
Jung
Jee H
JH
Choi
Jae Sue
JS
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry / Q000502:physiology; D006027:Glycosides / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D039821:Monoterpenes / Q000494:pharmacology*; D031653:Nelumbo / Q000737:chemistry / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D006027:Glycosides; D039821:Monoterpenes; D010936:Plant Extracts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat