title: Assessment of the effects of naringenin-type flavanones in uterus and vagina.
abstract: The potential utilization of plant secondary metabolites possessing estrogenic properties as alternatives to the classical hormone replacement therapy (HRT) for the relief of postmenopausal complaints asks for an evaluation regarding the safety in reproductive organs. In order to contribute to the estimation of the safety profile of the flavanones naringenin (Nar), 8‑prenylnaringenin (8PN) and 6‑(1,1‑dimethylally) naringenin (6DMAN), we investigated uterus and vagina derived from a three‑day uterotrophic assay in rats. Also, we investigated the metabolite profile resulting from the incubation of the three substances with liver microsomes. While no metabolites were detectable for naringenin, hydroxylation products were observed for 8PN and 6DMAN after incubation with human as well as rat liver microsomes. The parent compound naringenin did not evoke any estrogenic responses in the investigated parameters. A significant increase of the uterine wet weight, uterine epithelial thickness and proliferating vaginal cells was observed in response to 8PN, questioning the safety of 8PN if applied in the human situation. In contrast, no estrogenic effects on the reproductive organs were observed for 6DMAN in the conducted study, rendering it the compound with a more promising safety profile, therefore justifying further investigations into its efficacy to alleviate postmenopausal discomforts.
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany. Electronic address: Annekathrin.Keiler@tu-dresden.de.
authors.forename: Annekathrin Martina
authors.initials: AM
authors.lastname: Keiler
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Dörfelt
authors.affiliation: Cancer Research Center, Department of Biomedical Sciences, School of Public Health, University at Albany, Rensselear, NY, USA.
authors.forename: Namita
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Helle
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Manuela I
authors.initials: MI
authors.lastname: Bader
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Kretzschmar
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Kuhlee
authors.affiliation: Institute of Doping Analysis and Sports Biochemistry (IDAS), Kreischa, Dresden, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Thieme
authors.affiliation: Institute of Zoology, Molecular Cell Physiology and Endocrinology, Technische Universität Dresden, 01062 Dresden, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zierau
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects*
chemical_list: C119737:8-prenylnaringenin; D004967:Estrogens; D044950:Flavanones; D048789:Phytoestrogens; D004958:Estradiol; C005273:naringenin
keywords: 17β-Estradiol; 6-(1,1-Dimethylallyl)naringenin; 8-Prenylnaringenin; Estrogenicity; Naringenin; Uterus; Vagina