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Chrysin (5,7-dihydroxyflavone), a flavonoid present in diverse plants, has a backbone structure shared with the basic structure of the flavones, with additional hydroxyl groups that confers its antioxidant properties and effects at the GABAA receptor complex. However, whether these effects are due to the hydroxyl groups is unknown. Here we report the effects of chrysin or the flavone backbone (1 mg/kg) on rat behavior in the elevated plus-maze (EPM) and a locomotor activity test (LAT), as well as in the zebrafish light/dark test (LDT). Chrysin, but not flavone, increased entries and time in the open arms of the EPM, as well as time on white in the zebrafish LDT. These effects were comparable to diazepam, and were devoid of motor effects in both tests, as well as in the rat LAT. On the other hand, flavone increased risk assessment in the zebrafish LDT and rat EPM, suggesting effects threat information gathering; important species differences suggest new avenues of research. It is suggested that the specific effects of chrysin in relation to flavone are due to its free radical scavenging abilities and/or its action at the GABA A /benzodiazepine receptor complex.

Flavonoids are phenolic compounds found commonly in plants that protect them against the negative effects of environmental insults. These secondary metabolites have been widely studied in preclinical research because of their biological effects, particularly as antioxidant agents. Diverse flavonoids have been studied to explore their potential therapeutic effects in the treatment of disorders of the central nervous system, including anxiety and depression. The present review discusses advances in the study of some flavonoids as potential antidepressant agents. We describe their behavioral, physiological, and neurochemical effects and the apparent mechanism of action of their preclinical antidepressant-like effects. Natural flavonoids produce antidepressant-like effects in validated behavioral models of depression. The mechanism of action of these effects includes the activation of serotonergic, dopaminergic, noradrenergic, and γ-aminobutyric acid-ergic neurotransmitter systems and an increase in the production of neural factors, including brain-derived neurotrophic factor and nerve growth factor. Additionally, alterations in the function of tropomyosin receptor kinase B and activity of the enzyme monoamine oxidase A have been reported. In conclusion, preclinical research supports the potential antidepressant effects of some natural flavonoids, which opens new possibilities of evaluating these substances to develop complementary therapeutic alternatives that could ameliorate symptoms of depressive disorders in humans.

Introducción. La ansiedad patológica afecta la calidad de vida de quienes la padecen y cuando no es tratada adecuadamente puede dar paso a otras enfermedades psiquiátricas como la depresión. Su tratamiento farmacológico se basa en el uso de benzodiacepinas (ej. diazepam) y algunos antidepresivos con actividad ansiolítica (ej. fluoxetina). No obstante, un alto porcentaje de la población afectada por la ansiedad utiliza alternativas terapéuticas basadas en extractos de plantas. De ellas se han aislado, purificado y caracterizado químicamente principios activos con actividad ansiolítica, tal es el caso del flavonoide crisina. Este flavonoide ejerce efectos ansiolíticos semejantes al diazepam en modelos experimentales. Sin embargo, esos efectos se han estudiado bajo tratamiento agudo (una sola administración), pero el efecto del tratamiento a largo plazo sobre la ansiedad y la desesperanza conductual, así como los cambios en la actividad neuronal de estructuras cerebrales involucradas en la ansiedad y la depresión aún no ha sido explorado. Objetivo. Comparar los efectos del flavonoide crisina bajo tratamiento agudo y crónico sobre la ansiedad, el afrontamiento al estrés y su relación con la expresión de Fos en el núcleo septal lateral de la rata Wistar...