Estrogenic Activity of the Phytoestrogens Naringenin, 6-(1,1-Dimethylallyl)naringenin and 8-Prenylnaringenin

Abstract

Chemically synthesized naringenin derivatives, identical to natural occurring compounds, were tested for their estrogenic activity using two independent estrogen screening assays. Using a yeast based estrogen receptor assay, strong estrogenic activities were demonstrated for 6-(1,1-dimethylallyl)naringenin and 8-prenylnaringenin, while the parent compound naringenin did not show recognizable estrogenic activity. In MVLN cells, a bioluminescent MCF-7-derived cell line, the estrogenic activity of 8-prenylnaringenin and 6-(1,1-dimethylallyl)naringenin was detected at concentrations of 10(-6) M and 5 x 10(-6) M respectively. Naringenin demonstrated estrogenic activity but only at a concentration of 10(-5) M. These estrogenic effects are mediated by the ER, as the antiestrogen 4-hydroxytamoxifen inhibited these activities. In summary, this study provides the further confirmation that 8-prenylnaringenin demonstrates high estrogenic activity, and demonstrated for the first time for 6-(1,1-dimethylallyl)naringenin a reasonable high estrogenic activity, while naringenin exhibit low or no estrogenic activity.

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.…”

Time dependency of uterine effects of naringenin type phytoestrogens in vivo

“…On the other hand, high dietary intake from soy PEs has been demonstrated to be connected to positive effects on (peri-)menopausal complaints (Nagata et al, 2001). A group of recently described relatively potent phytoestrogens are of the naringenin type (Milligan et al, 1999;Milligan et al, 2002;Zierau et al, 2002). Especially 8-prenylnaringenin (8-PN) from hops, Humulus lupulus (L.) and beer, initially described as 8-isopentenylnaringenin (Kitaoka et al, 1998) has been characterized as an extremely potent phytoestrogen (Kitaoka et al, 1998;Milligan et al, 1999;Schaefer et al, 2003).…”

“…(Seo et al, 1997). We recently have described the estrogenic (Zierau et al, 2002) and Page 4 of 29 A c c e p t e d M a n u s c r i p t antiandrogenic properties of 6-DMAN (Zierau et al, 2003). For both naringenins low toxicity and weak cytostatic properties were reported, making them good candidate molecules for further studies (Tokalov et al, 2004).…”

Activation of Proestrogens from Hops (Humulus lupulus L.) by Intestinal Microbiota; Conversion of Isoxanthohumol into 8-Prenylnaringenin

“…These interesting properties have led to intense research aiming at deciphering various bioactivities. 8-PN showed in vivo estrogenic activity (4,5), prevented bone loss in rats (6), inhibited angiogenesis (7) and metastasis (8), and exhibited antiandrogenic activity (9).…”