Avaliação da bioatividade do flavonóide crisina em camundongos submetidos ao estresse crônico moderado e imprevisível

Abstract

The relationship between stress and depression has been subject of the intense behavioral and pathophysiological research. Within this context, studies have postulated that the hypersecretion of cortisol and the development of a framework of oxidative stress are factors responsible for the occurrence of depression in stressed individuals. As a recent study of mechanism, has also been suggested the role of the neurotrophins and of the enzyme Na+,K+-ATPase in the pathophysiology of depression. Although various antidepressants are already available on the market, the lack of efficacy in whole of patients and the wide occurrence of adverse side effects are a problematic in the treatment of depression. Thus, studies have investigated compounds, mainly natural, which can better meet the clinical requirements without causing undesirable physiological changes. Chrysin is a flavonoid abundant in natural, locally called, the bush passionfruit (Passiflora coerulea), and its therapeutic effects have been explored in models of oxidative stress, hyperlipidemia, inflammation, hypertension and cancer, but its effect on depression is still unknown. Thus, this study aimed to analyze the effect of oral treatment with the flavonoid chrysin for 28 days in non-stressed mice and mice subjected to chronic unpredictable mild stress (CUMS) in behavioral, biochemical and neurotrophic parameters, compared with the effect of fluoxetine (positive control). The CUMS applied for 28 days decreased the levels of BDNF and NGF and caused the inhibition of the , Na+,K+-ATPase activity in the hippocampus and prefrontal cortex of mice. Treatment with chrysin (5 or 20mg/kg) not only protected against these changes, but still 20mg/kg increased BDNF and NGF levels above the control group in non-stressed animals and in animals subjected to CUMS. The CUMS induced the reduction in the preference for sucrose, the increase in immobility time in forced swim test (FST) and the increase in plasma corticosterone levels. Besides crysin treatment (5 or 20mg/kg) prevent against these changes in stressed animals, also observed the antidepressant effect of chrysin in the FST in non-stressed animals. The aforementioned data show the effect of antidepressant of crysin in non-stressed and stressed animals, equivalently to fluoxetine, suggesting a possible involvement of NGF and BDNF in the antidepressant effect of chrysin. The protocol CUMS reduced levels of non-protein thiols (NPSH) and raised levels of reactive species (RS) in the hippocampus and prefrontal cortex of mice. As a possible mechanism of response to these changes, we observed the increase in the activity of enzymes glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) in the hippocampus and prefrontal cortex of mice subjected to CUMS. Treatment with chrysin (5 or 20mg/kg) protected against these changes, showing the involvement of antioxidant action in the antidepressant effect of chrysin in stressed animals. In conclusion, these data demonstrate the antidepressant effect of chrysin on behavioral and pathophysiological parameters in non-stressed and stressed animals, suggesting a possible involvement of BDNF and NGF in the antidepressant effect of chrysin. Still, this work exposes the passion fruit bush as an important target for the study of natural products in the combat of depression and other diseases of the central nervous system, showing the fundamentality of research of functionality and bioactive constitution these and other plants of this region.