Gallic Acid-Mediated Enhancement of Diazepam-Induced Sedation via GABA_A Receptor Modulation: In Vivo and In Silico...

Insomnia is a disorder that involves dissatisfaction with sleep and difficulty falling or staying asleep. This study aims to explore the sedative activity of gallic acid (GA) on thiopental sodium (TS)-induced sleep in mice. Intraperitoneal (i.p.) injections of GA (50, 100, and 200 mg/kg) and diazepam (DZP) (2 mg/kg) were given to Swiss albino mice individually or in combination. After administering TS, the onset and sleep duration were recorded. Additionally, GA's binding affinity (BA) with the GABA_A receptor (α1 and β2 subunits) was examined using molecular docking. Results revealed that GA significantly (p < 0.05) decreased onset and improved sleep duration in comparison to the control group in a dose-dependent manner. The highest dose of GA (GA-200) showed significant sedative activity with latency (1.77 ± 0.76 s) and sleep duration (182.28 ± 2.87 min). The combination of GA with DZP showed a synergistic sedative effect through decreasing latency and increasing sleep duration. In silico findings demonstrated that GA exhibited higher BA (-9.8 kcal/mol) against the GABA_A receptor (α1 and β2 subunits) compared to DZP (-8.4 kcal/mol). It also exhibited good pharmacokinetic characteristics and was less toxic than the DZP. Overall, our in vivo and in silico studies suggest that GA showed promising sedative activity. However, further investigation, including clinical trials, is needed to discover its medicinal potential.