Modulatory Anxiolytic Effect of Aucubin on Diazepam in Swiss Albino Mice: Possible Mechanisms Through In Vivo Approach with Receptor Binding Affinity

Aucubin is an iridoid glycosidic natural compound that is extracted from various plants, including Aucuba japonica, Veronica persica, and Eucommia ulmoides. This in vivo investigation was performed to evaluate the anxiolytic-like activity of aucubin on Swiss albino mice. For this, aucubin (2.5 and 5 mg/kg, p.o.) were ingested into the experimental animals, followed by various studies such as open field, swing, hole cross, and light–dark residence tests. In this research, diazepam served as a positive control, while the vehicle served as a negative control. In addition, a combination group (aucubin-5 + diazepam) was taken to determine the modulatory effect of aucubin on the standard drug diazepam. Furthermore, molecular docking was conducted to assess the binding intersection of aucubin and diazepam towards the α2 and α3 subunits of the GABA_A receptor, liable for the anxiolytic effect. Different computational methods were used to visualize the interaction between the ligands and receptors. The outcome of our investigation suggests that aucubin decreases the locomotor activity of the animals when compared to the control group, resulting in a calming effect on their behaviors. Moreover, aucubin demonstrated the potent binding value (–6.5 kcal/mol) to the α3 subunit of the GABA_A receptor via the formation of many hydrogen and hydrophobic interactions. Collectively, our results indicate that aucubin has a comparable impact on diazepam, and the molecule has an insignificant anxiolytic effect via interacting with the GABAergic system. We suggest conducting more clinical trials to establish the efficacy of aucubin as a dependable anxiolytic medication.