GabaAergic sedative prospection of sclareol-linalool co-treatment: An antagonistic intervention through in vivo and in silico studies

Abstract

Sleep disturbance causes many health problems in humans worldwide. This study evaluated the effects and possible mechanisms of sclareol (SCL) and/or linalool (LIN) through in vivo and in silico studies. For this, young chicks SCL (5, 10, and 20 mg/kg) and/or LIN (50 mg/kg) were orally administered thirty minutes before to the thiopental sodium (TS)-induced chicks with or without the standard drug diazepam (DZP: 3 mg/kg). Incidence, onset, and duration of sleep were then noted. The results suggest that SCL dose-dependently increased the onset and decreased the duration of sleep in animals. In contrast, LIN50 significantly (p < 0.05) decreased onset and increased sleep duration. SCL20 combined with LIN50 and/or DZP3 modulated the sleep parameters in animals. In combination, LIN50 showed better effects with DZP3, where the percentage decrease in latency and increase in sleep duration were 54.20 and 168.65 %, respectively. SCL20 when combined with LIN50 + DZP3 also modulated the onset and duration of sleep in animals. Further, in silico studies suggest that SCL and LIN have binding affinities with the 6X3X protein of the GABA_A receptor (α1 and β2 subunits) of −6.9 and −6.8 kcal/mol, respectively. The standard drug DZP showed a binding affinity of −5.0 kcal/mol. Taken together, SCL may exert an angiogenic-like effect and antagonize LIN and/or DZP-mediated sedative effects in TS-induced chicks, possibly through the GABA_A receptor α1 and β2 subunits interaction pathway.