Determination of rat urinary metabolites of icariin in vivo and estrogenic activities of its metabolites on MCF-7 cells
Liu, J.; Ye, H.; Lou, Y.
Die Pharmazie 60(2): 120-125
2005
ISSN/ISBN: 0031-7144 PMID: 15739900 Document Number: 590388
To confirm that the oestrogenic activity of icariin, a flavonoid glycoside from Epimedium sp., is based on the close relationship between the structures of its metabolites and the effects of their binding to target hormone receptors, the metabolism of icariin in rat urine was analysed in vivo, and the oestrogenic activity of its metabolites was measured in cultured MCF-7 human breast cancer cells, respectively. By CZE analysis, peaks corresponding to the relative positions of desmethylicaritin and icaritin were observed in the urine sample. Structural analysis following LC-ESI-MS revealed molecular ions [M-H]- of 512.8, 353.3 and 367.0 for metabolites consistent with those of icariside II, desmethylicaritin and icaritin, respectively. Icariin, icaritin and desmethylicaritin were analysed for their oestrogenicity using MCF7-cell proliferation (E-screen test). MCF-7 cells were cultured in an estradiol-free medium and then exposed to 10-8 to 10-5 mol/litre icariin and its metabolites, icaritin and desmethylicaritin, for 6 days. Icaritin and desmethylicaritin significantly increased cell proliferation, and the cell number increased from 1.61- to 4.14-fold compared with the untreated control, but the parent compound icariin failed to exhibit this effect. These results indicate that icariin is converted to icariside II, desmethylicaritin, and icaritin in vivo, and that the latter two act as a weak xeno-oestrogen on MCF-7 cells.