Because the prevailing form of
hormone replacement therapy is associated with the development of
cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated
hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL. (hops) have been reported to contain the prenylflavanone,
8-prenylnaringenin (8-PN), as the most estrogenic constituent, and this was confirmed using an
estrogen receptor ligand screening assay utilizing ultrafiltration mass spectrometry. Extracts of hops and red clover and their individual constituents including 8-PN,
6-prenylnaringenin (6-PN),
isoxanthohumol (IX), and
xanthohumol (XN) from hops and
daidzein,
formononetin,
biochanin A, and
genistein from red clover were compared using a variety of in vitro estrogenic assays. The IC50 values for the
estrogen receptor alpha and beta binding assays were 15 and 27 microg/mL, respectively, for hops and 18.0 and 2.0 microg/mL, respectively, for the red clover extract. Both of the extracts,
genistein, and 8-PN activated the
estrogen response element (ERE) in Ishikawa cells while the extracts,
biochanin A,
genistein, and 8-PN, significantly induced ERE-
luciferase expression in MCF-7 cells. Hop and red clover extracts as well as 8-PN up-regulated
progesterone receptor (PR)
mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR
mRNA was significantly up-regulated by the extracts,
biochanin A,
genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 microg/mL, respectively, in the
alkaline phosphatase induction assay. On the basis of these data, hops and red clover could be attractive for the development as herbal dietary supplements to alleviate menopause-associated symptoms.