Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies

SM Hafiz Hassan; Heba A.S. El-Nashar; Md Anisur Rahman; Md Jannatul Islam Polash; Mehedi Hasan Bappi; Milon Mondal; Mostafa A. Abdel-Maksoud; Abdul Malik; Mohammed Aufy; Mohamed El-Shazly; Muhammad Torequl Islam

doi:10.1016/j.biopha.2024.116939

Titel

Sclareol antagonizes the sedative effect of diazepam in thiopental sodium-induced sleeping animals: In vivo and in silico studies

Autor*in

SM Hafiz Hassan

Department of Chemistry and Biochemistry, Miami University

Heba A.S. El-Nashar

Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University

Md Anisur Rahman

Department of Pharmacy, Islamic University, Kushtia

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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 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 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 compounds Results 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.

Stichwort

DiazepamSleep disordersSedationSclareolGABA receptorMolecular docking

Objekt-Typ

journal article

Sprache

Englisch [eng]

Persistent identifier

phaidra.univie.ac.at/o:2086362

DOI

10.1016/j.biopha.2024.116939

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