Avaliação do efeito do extrato hidroalcoólico do caroço da Euterpe oleracea Mart. (açaí) em modelo experimental de depressão

Abstract

The World Health Organization (WHO) demonstrated that depression affects about 20% of the world's population. Evidence from our group showed that the hydroalcoholic extract of Euterpe oleracea Mart. (ASE), rich in polyphenols, has an antihypertensive, antioxidant and vasodilator effects. The aim of the study was to investigate the antidepressant potential of ASE by comparing it with fluoxetine (FLU), a selective serotonin reuptake inhibitor with well-established antidepressant effects. Female Wistar rats were placed to mate, and after birth the male offspring were separated into nine experimental groups: control (CON, water), CON + ASE (200mg / kg / day), CON + FLU ( 20mg / kg / day ); chronic maternal separation (SMC, water); SMC + ASE (200 mg / kg / day), SMC + FLU (20 mg / kg / day); single maternal separation (SMU, water), SMU + ASE (200 mg / kg / day) and SMU + FLU (20 mg / kg / day). The SMC protocol started on the second post-natal day (PN2), the pups were separated from their mothers during 3 hours for 14 days. The SMU protocol also started on day PN2 and the pups were separated from their mothers for 8 minutes, only once. From day PN76, treated groups received ASE or fluoxetine by intragastric gavage. Porsolt and open field behavioral tests were performed. After euthanasia, the animals’ blood was collected for the detection of CRH and GR plasma levels; the adrenal glands were removed for the detection of the monoamines dopamine (DA) and norepinephrine (NE), and in the homogenate of the hypothalamus was quantified the TrkB by ELISA. The protein expression of GR, PDE5, PPARγ, pro-BDNF and BDNF was performed by western blotting on the hypothalamus and hippocampal homogenates. The analysis of oxidative damage and enzymatic activity were performed by spectrophotometry in brainstem homogenate. For the groups that were not submitted to maternal separation, the ASE and FLU treatments reduced the immobility time and the GR expression in the hypothalamus. ASE reduced CRH levels, and increased NE, DA, and TRKB levels. However, FLU increased CRH levels and reduced DA and TRKB levels, elevated oxidative damage, and reduced GPx activity and nitrite levels. The SMC and SMU groups showed increased oxidative damage, reduced antioxidant activity, as well as lower expression of BDNF, GR, PDE5, and PPARγ. ASE and FLU treatments reduced oxidative damage, CRH levels, and increased levels of DA, nitrite and antioxidant activity in animals submitted to maternal separation. Only the ASE was able to increase the expression of PPARγ and GR, as well as to enhance the levels of TRKB in depressed animals. The FLU treatment, unlike the ASE, increased BDNF expression. Our results indicate that ASE reduced the deleterious effects of maternal separation through its antioxidant effect, reduced HPA axis activation, increased neurotransmitters and proteins essential for negative neuromodulation of depression, demonstrating antidepressant potential.