Phytoestrogenic Activity of Blackcurrant Anthocyanins Is Partially Mediated through Estrogen Receptor Beta

Phytoestrogens are plant compounds with estrogenic effects found in many foods. We have previously reported phytoestrogen activity of blackcurrant anthocyanins (cyanidin-3-glucoside, cyanidin-3-rutinoside, delphinidin-3-glucoside, and delphinidin-3-rutinoside) via the estrogen receptor (ER). In this study, we investigated the participation of ER in the phytoestrogen activity of these anthocyanins. Blackcurrant anthocyanin induced ER-mediated transcriptional activity, and the IC50 of ER was lower than that of ER, indicating that blackcurrant anthocyanins have a higher binding affinity to ER. In silico docking analysis of cyanidin and delphinidin, the core portions of the compound that fits within the ligand-binding pocket of ER, showed that similarly to 17-estradiol, hydrogen bonds formed with the ER residues Glu305, Arg346, and His475. No fitting placement of glucoside or rutinoside sugar chains within the ligand-binding pocket of ER-estradiol complex was detected. However, as the conformation of helices 3 and 12 in ER varies depending on the ligand, we suggest that the surrounding structure, including these helices, adopts a conformation capable of accommodating glucoside or rutinoside. Comparison of ER and ER docking structures revealed that the selectivity for ER is higher than that for ER, similar to genistein. These results show that blackcurrant anthocyanins exert phytoestrogen activity via ER.