Anxiolytic-like effect of daidzin possibly through GABAA receptor α2 and α3 subunits interaction pathway: In vivo and in silico studies

The soy plant-derived isoflavone daidzin (DZN) has diverse biological activities, including neuroprotective (e.g., memory-enhancing and antiepileptic) effects. This study emphasizes evaluating the anxiolytic effect of DZN on mice. Additionally, in silico investigations were also carried out to check the potential molecular mechanisms for the anxiolytic effect of DZN. For this, adult male Swiss albino mice were intraperitoneally (i.p.) treated with DZN (5, 10, and 20 mg/kg) with or without the standard GABAergic agonist drug diazepam (DZP: 2 mg/kg) and/or antagonist drug flumazenil (FLU: 0.1 mg/kg) and checked for different locomotor behaviors using various mouse models. The molecular docking study of DZN was conducted against GABA_A receptor subunits. Findings suggest that DZN dose-dependently and significantly (p <0.05) increased locomotor activities such as the number of field crosses, hole crosses, swings, grooming, and light residence time while decreasing the rearing of the animals. With DZP, it significantly (p <0.05) reduced the test parameters, while altering these parameters with FLU. Our molecular docking studies demonstrate that DZN has a strong binding affinity of −7.4 and −6.9 kcal/mol for α2 and α3 subunits of the GABA_A receptor, respectively, whereas the standard drugs DZP and FLU showed binding affinities between −6.0 and −6.7 kcal/mol for these subunits. Taken together, DZN augmented the anxiolytic effect of DZP while reducing the effect of FLU in mice. We suppose that DZN may show anxiolytic-like effects on Swiss mice, possibly through α2 and α3 subunits of the GABA_A receptor interaction pathway.