Bioactivity-guided isolation of acetylcholinesterase inhibiting constituents of the flowers of Bride's Feathers (Aruncus dioicus)

Abstract

Acetylcholinesterase (AChE) inhibition is the main strategy in the clinical management of Alzheimer's disease. Natural products have already established themselves as an excellent source for AChE inhibiting compounds (e.g. galantamine, huperzine A), but new substances with better efficacy and less side effects are still demanded. The aim of the performed study was a bioactivity-guided isolation of constituents of the aerial parts of Bride's Feathers (Aruncus dioicus (Walter) Fernald, Rosaceae) in order to obtain novel AChE inhibitors. The activity of the obtained extracts and sub-fractions was monitored by an in vitro enzyme inhibition assay based on the method of Ellman [1]. Investigations of extracts of different polarity and from varying plant parts identified a methanolic extract of the flowers as ideal starting material. Activity guided isolation afforded several active principals with moderate activity e.g. quercetin-3-O-β-D-galactopyranoside (=hyperin), quercetin-3-O-β-D-glucopyranoside (=isoquercitrin), 4'-O-methylquercetin-3-O-β-D-galactopyranoside (=tamarixetin-3-O-β-D-galactoside), 3'-O-methylquercetin-3-O-β-D-glucopyranoside (=isorhamnetin-3-O-β-D-glucopyranoside) as well as a mixture of 3,4-dicaffeoyl-α-D-glucopyranoside and 3,4-dicaffeoyl-β-D-glucopyranoside. Among them the isomer-mixture of caffeic acid glucosides showed the highest activity with an IC50 value of 67.8µM (CI95: 50.8–90.2µM). Isolation of two further inactive but prominent compounds resulted in the identification of two new monoterpene lactone glucosides: aruncolactonoside (=4R*-hydroxy-5S*-(2-methylprop-1-enyl)-3-(2-(β-D-glucopyranosyloxy)-ethylid-E-en)-dihydrofuran-2(3H)-one and isoaruncolactonoside (=4R*-hydroxy-5S*-(2-methylprop-1-enyl)-3-(2-(β-D-glucopyranosyloxy)ethylid-Z-en)-dihydro-furan-2(3H)-one).