Synergistic Hypnotic Effects of Sesamol and Thymol Possibly through GABAergic Interaction Pathway: In Vivo and In Silico Studies

Abstract

Background: Sleep is essential to human homeostasis and affects the immune system. Sleep disorders are a group of conditions that disturb normal sleep patterns and can affect overall health, safety, and quality of life. Poor or insufficient sleep has been associated with various dysfunctions in most body systems, such as endocrine, metabolic, higher cortical function, and neurological disorders. This study aims to evaluate the effects of the natural plant derivatives Sesamol (SES) and Thymol (THY) on sodium pentobarbital-induced sleeping mice. Methodology: The animals were given Sesamol (SES) (25, 50 mg/kg), Thymol (THY) (30 mg/kg), Diazepam (DZP) (3 mg/kg), and Caffeine (CAF) (10 mg/kg) orally (p.o.) in the respective groups individually and in combination. After 30 minutes, the treated mice were given sodium thiopental (10 mg/kg) intraperitoneally (i.p.) to induce sleep, and latency of sleeping time and duration were observed. Additionally, an in silico study was undertaken to predict the involvement of gamma-aminobutyric acid (GABA) receptors in the sleep mechanism. Results: In the current study, we observed that SES and THY increased the duration of sleeping time and decreased the latency of sleep induction. When SES, DZP, and THY were administered together, they demonstrated the greatest hypnotic activity. SES and THY exhibited strong binding affinity with different GABA receptor subtypes in in silico studies. The pharmacokinetic analysis of SES and THY using SwissADME indicated good absorption, distribution, metabolism, and excretion properties. Conclusions: SES and THY produced a hypnotic-like effect in the mice model, possibly through the GABA_A and GABA_B receptor interaction pathways.