GABAergic antidepressant effect of daidzin: in vivo approach with in silico receptor binding affinities.

Daidzin (DZN: 7-(β-D-Glucopyranosyloxy)-4-hydroxyisoflavone) is a soy plant-derived isoflavone. It has diverse biological activities, including nephroprotective effects. To date, its anxiolytic, memory-enhancing, and antiepileptic properties have been discovered. However, its antidepressant activity has not yet been investigated.This study aimed to investigate DZN's antidepressant activity through animal and in silico studies. Male Swiss albino mice were randomly divided into nine groups consisting of control (vehicle), DZN 5, 10, and 20mg/kg, diazepam (GABA_A agonist), flumazenil (GABA_A antagonist), and a combination of DZN-10 with diazepam and/or flumazenil. Additionally, in silico studies were also performed to understand the possible molecular mechanisms behind this neurological activity. Findings suggest that DZN dose-dependently and significantly (p < 0.05) enhanced immobility time (IMT) in animals. DZN-10 also increased diazepam's effects significantly (p < 0.05), possibly by raising its IMT values. However, DZN significantly (p < 0.05) declined flumazenil's effect in their combination. In silico findings suggest that DZN has a strong binding affinity against GABA_A receptor subtypes. We suppose DZN exerts its antidepressant effect, possibly by interacting with GABA_A receptors. It exerts a synergistic effect with the GABA agonist drug diazepam. Further studies are required to determine the exact molecular mechanism behind this neurological activity.