Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats

<b>Background</b>: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with...

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Main Authors: Juan Francisco Rodríguez-Landa, Oscar Jerónimo Olmos-Vázquez, Carlos Fabrizio Quiñonez-Bailón, Gabriel Guillén-Ruiz, Ana Karen Limón-Vázquez, Jonathan Cueto-Escobedo, Eduardo Rivadeneyra-Domínguez, Blandina Bernal-Morales
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Language:English
Published: MDPI AG 2025-05-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/5/311
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author Juan Francisco Rodríguez-Landa
Oscar Jerónimo Olmos-Vázquez
Carlos Fabrizio Quiñonez-Bailón
Gabriel Guillén-Ruiz
Ana Karen Limón-Vázquez
Jonathan Cueto-Escobedo
Eduardo Rivadeneyra-Domínguez
Blandina Bernal-Morales
author_facet Juan Francisco Rodríguez-Landa
Oscar Jerónimo Olmos-Vázquez
Carlos Fabrizio Quiñonez-Bailón
Gabriel Guillén-Ruiz
Ana Karen Limón-Vázquez
Jonathan Cueto-Escobedo
Eduardo Rivadeneyra-Domínguez
Blandina Bernal-Morales
author_sort Juan Francisco Rodríguez-Landa
collection DOAJ
description <b>Background</b>: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with a potential risk of developing estrogen-dependent cancers through interactions with estrogen receptor α (ERα). Alternatively, genistein produces estrogenic effects in animals and humans at dietary dosages that act on the nuclear and membrane ERα, estrogen receptor β (ERβ), and the G-protein-coupled estrogen receptor (GPER). These receptors are likely involved in the anxiety symptoms observed in premenstrual disorders. The objective of this study was to evaluate the effects of genistein and 17β-estradiol on anxiety-like behavior and the plasma concentrations of estradiol and progesterone throughout the ovarian cycle of Wistar rats. <b>Methods</b>: The effect of the administration of 0.09 mg/kg of genistein or 17β-estradiol was evaluated using the elevated plus maze (EPM) test, locomotor activity test (LAT), and light/dark box (LDB) test, as well as by assessing the plasma concentrations of estradiol and progesterone, while considering the ovarian cycle phases. <b>Results</b>: Higher levels of anxiety-like behavior were detected in the metestrus–diestrus phase compared to the proestrus–estrus phase, which was associated with low concentrations of estradiol. Genistein, similarly to 17β-estradiol, significantly reduced anxiety-like behaviors in the EPM and LDB; however, 17β-estradiol, but not genistein, significantly increased the plasma estradiol concentration. No significant changes were found in locomotor activity or the plasma progesterone concentrations due to the treatments. <b>Conclusions</b>: These findings suggest that genistein may be useful in the development of alternative therapies to reduce the anxiety associated with low steroid hormone concentrations, which occur in premenstrual syndrome. Genistein could be an alternative to steroidal estrogen therapy to avoid potential side effects due to estradiol or antidepressant treatments, although it still requires medical care.
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spelling doaj-art-7f40578f02f5453fb2c3be337f5433f82025-08-20T01:56:24ZengMDPI AGMetabolites2218-19892025-05-0115531110.3390/metabo15050311Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar RatsJuan Francisco Rodríguez-Landa0Oscar Jerónimo Olmos-Vázquez1Carlos Fabrizio Quiñonez-Bailón2Gabriel Guillén-Ruiz3Ana Karen Limón-Vázquez4Jonathan Cueto-Escobedo5Eduardo Rivadeneyra-Domínguez6Blandina Bernal-Morales7Laboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoDepartamento de Investigación Clínica y Traslacional, Instituto de Ciencias de la Salud, Universidad Veracruzana, Xalapa 91190, Veracruz, MexicoFacultad de Química Farmacéutica Biológica, Universidad Veracruzana, Xalapa 91000, Veracruz, MexicoLaboratorio de Neurofarmacología, Instituto de Neuroetología, Universidad Veracruzana, Xalapa 91190, Veracruz, Mexico<b>Background</b>: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with a potential risk of developing estrogen-dependent cancers through interactions with estrogen receptor α (ERα). Alternatively, genistein produces estrogenic effects in animals and humans at dietary dosages that act on the nuclear and membrane ERα, estrogen receptor β (ERβ), and the G-protein-coupled estrogen receptor (GPER). These receptors are likely involved in the anxiety symptoms observed in premenstrual disorders. The objective of this study was to evaluate the effects of genistein and 17β-estradiol on anxiety-like behavior and the plasma concentrations of estradiol and progesterone throughout the ovarian cycle of Wistar rats. <b>Methods</b>: The effect of the administration of 0.09 mg/kg of genistein or 17β-estradiol was evaluated using the elevated plus maze (EPM) test, locomotor activity test (LAT), and light/dark box (LDB) test, as well as by assessing the plasma concentrations of estradiol and progesterone, while considering the ovarian cycle phases. <b>Results</b>: Higher levels of anxiety-like behavior were detected in the metestrus–diestrus phase compared to the proestrus–estrus phase, which was associated with low concentrations of estradiol. Genistein, similarly to 17β-estradiol, significantly reduced anxiety-like behaviors in the EPM and LDB; however, 17β-estradiol, but not genistein, significantly increased the plasma estradiol concentration. No significant changes were found in locomotor activity or the plasma progesterone concentrations due to the treatments. <b>Conclusions</b>: These findings suggest that genistein may be useful in the development of alternative therapies to reduce the anxiety associated with low steroid hormone concentrations, which occur in premenstrual syndrome. Genistein could be an alternative to steroidal estrogen therapy to avoid potential side effects due to estradiol or antidepressant treatments, although it still requires medical care.https://www.mdpi.com/2218-1989/15/5/311anxietypremenstrual syndromephytoestrogensalternative therapyovarian cyclerat
spellingShingle Juan Francisco Rodríguez-Landa
Oscar Jerónimo Olmos-Vázquez
Carlos Fabrizio Quiñonez-Bailón
Gabriel Guillén-Ruiz
Ana Karen Limón-Vázquez
Jonathan Cueto-Escobedo
Eduardo Rivadeneyra-Domínguez
Blandina Bernal-Morales
Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
Metabolites
anxiety
premenstrual syndrome
phytoestrogens
alternative therapy
ovarian cycle
rat
title Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
title_full Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
title_fullStr Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
title_full_unstemmed Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
title_short Genistein Reduces Anxiety-like Behavior During Metestrus–Diestrus Phase Without Changing Estradiol or Progesterone Levels in Wistar Rats
title_sort genistein reduces anxiety like behavior during metestrus diestrus phase without changing estradiol or progesterone levels in wistar rats
topic anxiety
premenstrual syndrome
phytoestrogens
alternative therapy
ovarian cycle
rat
url https://www.mdpi.com/2218-1989/15/5/311
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