Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies.
Biomed Pharmacother
; 176: 116939, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38870629
ABSTRACT
BACKGROUND:
Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis.METHODS:
The control, sclareol (5, 10 and 20â¯mg/kg), and the reference drugs [diazepam 3â¯mg/kg and Caffeine (CAF) 10â¯mg/kg] were used in male albino mice. Then, sodium thiopental (40â¯mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compoundsRESULTS:
SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABAA receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABAA receptor subunits A2 and A5.CONCLUSIONS:
Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article