# Antidepressant-Like Activity of Naringenin, an Important Agro-Industrial Resource, Complexed with β‑Cyclodextrin

## TL;DR

This study shows that naringenin, when complexed with β-cyclodextrin, has antidepressant-like effects in mice, possibly through dopamine and noradrenaline systems.

## Contribution

The novel finding is the antidepressant-like activity of naringenin-β-cyclodextrin complex and its mechanism involving dopaminergic and noradrenergic pathways.

## Key findings

- Naringenin and its β-cyclodextrin complex reduced immobility time in mice, similar to imipramine.
- The effect was blocked by D2 and α2-adrenoceptor antagonists, suggesting dopamine and noradrenaline involvement.
- No change in locomotor activity was observed, indicating a specific antidepressant-like effect.

## Abstract

The objective of this work was to investigate the effect
on the
central nervous system (CNS) of naringenin (NR) and of the inclusion
complex obtained with its incorporation into β-cyclodextrin
(NR-βCD) in mice, using experimental models. The possible participation
of the monoaminergic system in the antidepressant activity of NR was
also studied. NR and NR-βCD, when administered acutely (20 and
40 mg/kg, p.o.), produced a significant reduction in the immobility
time (p < 0.05), an effect comparable to imipramine
(30 mg/kg, p.o.). The reduction in immobility time observed after
NR treatment (20 mg/kg, p.o.) was prevented by pretreatment with haloperidol
(0.2 mg/kg, i.p., a D2 receptor antagonist) and yohimbine
(Yob) (1 mg/kg, i.p., an α2-adrenoceptor antagonist),
but not with ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist).
In summary, NR and NR-βCD produced an antidepressant-like effect
with no change in locomotor activity. Furthermore, this anti-immobility
effect seems to be mediated by interaction with dopaminergic and noradrenergic
systems.