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

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.