In vivo evaluation of estrogenic effects of dietary supplement Hops.

ZANARDI MV; GUENTHER T; VOLLMER G; VARAYOUD J; DURANDO M; ZIERAU O

Simposio; International Symposium on Reproductive Health.; 2021

Hops is used as a suspected safe alternative to hormone replacement therapy for menopausal symptoms relief. Hops contains, among others, the phytoestrogen 8-prenylnaringenin (8-PN) and xantohumol (XN), which can be metabolized to 8-PN. XN acts as a cancer chemopreventive agent. We aimed to evaluate the estrogenic properties of hops and knockout hops (KO-hops) (reduced in XN and consequently in 8-PN) using the uterotrophic assay. Seven weeks old female Wistar rats were bilaterally ovariectomized. After fourteen days, rats were treated for three days with 17ß-estradiol (E2: 4 μg/kg bw/day) or fed with the vehicle (CON), hops or KO-hops at 8, 40 and 200 mg/kg bw/day. Animals were sacrificed 24 h after the last treatment day. The uterus was removed, weighed and processed for histology and mRNA extraction. As expected, the relative uterine weight (rUW) and luminal epithelial cell height (LECH) were increased by the positive control E2 respect to CON (p < 0.05). The rUW was similar between hops, KO-hops and CON groups. An increase in LECH was shown i n hops40 compared to CON (p < 0.05). E2 and KO-hops8 induced cell proliferation in the luminal epithelium compared to CON (p < 0.05). The mRNA expression of estrogen receptor a (Esr1) and complement C3 (C3) was downregulated and upregulated, respectively by E2 treatment (p < 0.05). Esr1 and C3 mRNA were changed neither by hops nor by KO-hops with respect to the CON. The mRNA expression of progesterone receptor was similar between all evaluated groups. In general, no uterotrophic effects were observed in the endometrium in response to hops extracts, independently of their composition. In conclusion, the absence of uterine estrogenic effects provides evidence for the safety of both extracts. These preliminary results encourage us to study hops extracts for its chemopreventive properties, although more experiments are needed.