Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin.
The female flowers of the hop plant (hop cones) are used as a preservative and as a flavouring agent in beer. A novel phyto-oestrogen, 8-prenylnaringenin, was recently identified in hops and this study was undertaken to characterize the oestrogenic activity of this compound using a combination of in vitro and in vivo assays. Natural and semi-synthetic 8-prenylnaringenin showed similar bioactivities both in a yeast screen transfected with the human oestrogen receptor and in oestrogen-responsive human Ishikawa Var-I cells. 8-Prenylnaringenin showed comparable binding activity to both oestrogen receptor isoforms (ER alpha and ER beta). 8-Prenylnaringenin extracted from hops contains similar amounts of both (R)- and (S)- enantiomers, indicating that the compound is normally formed non-enzymatically. Both enantiomers showed similar bioactivity in vitro and similar binding characteristics to ER alpha and ER beta. The oestrogenic activity of 8-prenyl-naringenin in vitro was greater than that of established phyto-oestrogens such as coumestrol, genistein and daidzein. The high oestrogenic activity was confirmed in an acute in vivo test using uterine vascular permeability as an end point. When the compound was given to ovariectomized mice in their drinking water, oestrogenic stimulation of the vaginal epithelium required concentrations of 100 mug ml(-1) (about 500-fold greater than can be found in any beer).
Milligan
S
S
Endocrinology and Reproduction Research Group, School of Biomedical Sciences, King's College, Guy's Campus, London SE1 1UL, UK. Stuart.Milligan@kcl.ac.uk
Kalita
J
J
Pocock
V
V
Heyerick
A
A
De Cooman
L
L
Rong
H
H
De Keukeleire
D
D
D000818:Animals; D001681:Biological Assay; D002199:Capillary Permeability / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D027582:Humulus; D007536:Isomerism; D051379:Mice; D008815:Mice, Inbred Strains; D010936:Plant Extracts / Q000494:pharmacology; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000098:blood supply / Q000187:drug effects; D014621:Vagina / Q000187:drug effects
C119737:8-prenylnaringenin; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D044950:Flavanones; D005419:Flavonoids; D006728:Hormones; D010936:Plant Extracts; D011960:Receptors, Estrogen