Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin

Abstract

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).

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

“…Furthermore, 8-PN and IX were also evaluated since 8-PN is the major active phytoestrogen in H. lupulus [16,17,20,21], and IX can be metabolized to 8-PN [22]. The major phytoestrogens in T. pratense, daidzein and genistein, and their metabolic precursors, formononetin and biochanin A, were not evaluated since there is already a large body of data on these compounds [36,37], and the primary focus was on H. lupulus.…”

“…The most potent estrogen in H. lupulus is 8-PN, which is in actuality an artifact formed through isomerization of the precursor chalcone, desmethylxanthohumol [18,19]. 8-Prenylnaringenin has been shown in a variety of in vitro assays to be estrogenic in the nanomolar range [16,17,20,21]. It can also be formed from precursors such as IX, and xanthohumol (XH), through metabolism [22].…”

The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties

“…Gray of the Annonaceae (Kitaoka et al, 1998). Subsequent investigations in vitro followed, and to date 8PN has generally been shown to mimic the action of 17β-estradiol, albeit with a lesser (10-to 20,000-fold) potency (Coldham and Sauer, 2001;Milligan et al, 2002;Milligan et al, 2000;Rong et al, 2001;Zierau et al, 2002). It is a potent ligand for the α-estrogen receptor with an IC 50 value in the nanomolar range (Kitaoka et al, 1998), it stimulates the production of alkaline phosphatase in Ishikawa cells (Milligan et al, 1999), and stimulates the growth of estrogen-dependent MCF7 (Kitaoka et al, 1998) breast cancer cells.…”

Isohumulones, Bitter Acids Derived from Hops, Activate Both Peroxisome Proliferator-activated Receptor α and γ and Reduce Insulin Resistance

“…A recent study demonstrated that the plant sterol guggulusterone, derived from Commiphora mukul (guggulu in Sanskrit), which has been used in Ayurvedic medicine, acts as an antagonist for the nuclear hormone receptor, farnesoid X receptor, and lowers low density lipoprotein levels in rodents and humans (36). Hops, which have been used as an herbal medicine for many years, were shown to contain several compounds that have significant biological effects, such as 8-prenylnaringenin, which has estrogenic activity (37), and xanthohumol and hexahydro-colupulone, which were shown to inhibit the growth of cancers (38). Humulone was also shown to have anti-tumor effects (10,11,39).…”