Efeito antidepressivo do complexo de inclusão contendo o flavonoide naringenina em B-Ciclodextrina: evidências para o envolvimento do sistema monoaminérgico

Abstract

Naringenin is a flavonoid present in citrus fruits and has several pharmacological activities proven as anti-inflammatory, antidiabetic, hepatoprotective, cardioprotective, neuroprotective, among others. However, naringenin has low solubility that can be minimized with carriers such as cyclodextrins. The objective of this study was to evaluate the anti-depressant activity of flavonoid naringenin and naringenin-β-cyclodextrin (NR-βCD) inclusion complex at doses of 20 and 40 mg/kg p.o. in mice. The animals received acute treatment and were evaluated in forced swimming test (FST), tail suspension test (TST) and open field (OFT) tests. Pretreatment with haloperidol (0.2 mg/kg, i.p., D2 receptor antagonist), yohimbine (1 mg/kg, i.p., α2 adrenergic receptor antagonist) and ondansetron (1 mg/kg, i.p., 5-HT3) were used to investigate the involvement of the monoaminergic system. It was observed that NR and NRβCD (20 and 40 mg/kg, p.o), produced a significant reduction in the duration of immobility time in FST and TST. Pretreatment with haloperidol and yohimbine in NF demonstrated that the reduction in immobility time observed in NR treatment (20 mg/kg, p.o.) was reversed, but not by the ondansetron. The results demonstrated that the acute treatment with flavonoid and its complex have antidepressant effect in both tests without interference of the locomotor activity of the animals in the OFT, with possible mediation of the dopaminergic (D2 receptor) and noradrenergic (α2 adrenergic receptor) systems. Additionally, it is suggested that the NRβCD inclusion complex is a promising agent and has biotechnological value in the treatment of depression.