Trans-Ferulic acid reduces the sedative activity of diazepam in thiopental sodium-induced sleeping mice: A potential GABAergic transmission

Abstract

trans-Ferulic acid (TFA), a bioactive compound found in many plants, has been recognized for its diverse pharmacological activities, including potential neurological benefits. Previous studies suggest that TFA exerts anxiolytic effects via GABAergic pathways. This study aimed to investigate the sedative effects of TFA and its possible molecular mechanisms through in vivo and in silico approaches. Adult Swiss mice were randomly divided into six groups (n = 7): control (vehicle), standard (DZP: Diazepam at 3 mg/kg, p.o.), three test groups (TFA at 25, 50, and 75 mg/kg, p.o.), and a combination group (TFA: 50 mg/kg with DZP: 3 mg/kg, p.o.). Thirty minutes post-treatment, thiopental sodium (TS) at 40 mg/kg was administered to induce sedation, and latency as well as duration of sleep, were observed for up to 4 h. In silico studies were conducted with GABA_A receptor subunits (α1 and β2) to elucidate the possible molecular interactions. The results demonstrated that TFA significantly reduced latency and extended sleep duration in a dose-dependent manner compared to the control. Additionally, TFA combined with DZP further significantly (p < 0.001) enhanced these effects. In silico analysis revealed that TFA and DZP exhibited strong binding affinities with the GABA_A receptor subunits (α1 and β2) in the identical binding sites, with binding energies of −6.8 and − 8.7 kcal/mol, respectively. Collectively, TFA exerted a mild sedative effect in TS-induced sleeping mice and modulated the activity of DZP, likely through interactions with GABA_A receptors. TFA showed promising activity as a potential candidate for managing sleep disorders such as insomnia.