Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): Structure-requirement of hydroxyanthraquinones for estrogenic activity

The methanolic extract from the roots of Polygonum (P.) cuspidatum was foun d to enhance cell proliferation at 30 or 100 mug/mL in MCF-7, an estrogen-s ensitive cell line. By bioassay-guided separation from P. cuspidatum with t he most potent activity, emodin and emodin 8-O-beta -D-glucopyranoside were isolated as active principles. The methanolic extracts from Polygonum, Cas sia, Aloe, and Rheum species, which were known to contain anthraquinones, a lso showed the MCF-7 proliferation. As a result of the evaluation of variou s anthraquinones from plant sources and synthetic anthraquinones, aloe-emod in, chrysophanol, chrysophanol 8-O-beta -D-glucopyranoside, and 1.8-dihydro xyanthraquinone showed weak activity. On the other hand, alizalin and 2,6-d ihydroxyanthraquinone as well as emodin having the 2- and/or 6-hydoxyl grou ps showed potent activity. These results show that the unchelated hydroxyl group is essential for strong activity. Emodin and 2,6-dihydroxyanthraquino ne also inhibited 17 beta -estradiol binding to human estrogen receptors (E Rs) with K-i values of 0.77 and 0.31 muM for ER alpha and 1.5 and 0.69 muM For ERP. These findings indicate that hydroxyanthraquinones such as emodin are phytoestrogens with an affinity to human estrogen receptors. (C) 2001 E lsevier Science Ltd. All rights reserved.