Ligand binding affinities of arctigenin and its demethylated metabolites to estrogen receptor alpha

Abstract

Phytoestrogens are defined as plant-derived compounds with estrogen-like activities according to their chemical structures and activities. Plant lignans are generally categorized as phytoestrogens. It was reported that (-)-Arctigenin, the aglycone of arctiin, was demethylated to (-)-dihydroxyenterolactone (DHENL) by Eubacterium (E.) sp. ARC-2. Through stepwise demethylation, E. sp. ARC-2 produced six intermediates, three monodesmethylarctigenins and three di-desmethylarctigenins. In the present study, ligand binding affinities of (-)-Arctigenin and its seven metabolites, including DHENL, were investigated for an estrogen receptor alpha, and found that demethylated metabolites had stronger binding affinities than (-)-Arctigenin using a ligand binding screen assay method. The IC50 value of (2R,3R)-2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dihydroxybenzyl)- butyrolactone was 7.9 × 10-4 M. © 2013 by the authors.