Selective cholinesterase inhibitory activities of a new monoterpene diglycoside and other constituents from Nelumbo nucifera stamens

Abstract

A new β -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-β-D-glucopyranosyl- (1→6)-β -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 β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) inhibition assays. Compounds 1-3 and 5 showed good and noncompetitive inhibition against AChE with IC50 values of 11.89, 20.07, 4.55, and 3.20μM and Ki values of 15.71, 25.44, 7.76, and 5.76μM, respectively. Compounds 1, 2, and 5 also possessed BChE inhibitory activities with IC50 values of 13.93, 62.29, 205.78, and 83.06μM, respectively. The selectivity index (SI) values of 1, 2, 3, and 5, calculated from IC50 values of BChE and AChE, were 1.2, 3.1, 45.7, and 26.0. However, all isolated compounds lacked BACE1 inhibition up to 100μM. Therefore, N. nucifera stamens-derived compounds could potentially exert their primary anti-Alzheimer effects as AChE inhibitors rather than BACE1 inhibitors. © 2010 Pharmaceutical Society of Japan.