Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway

Abstract

Sedatives promote calmness or sleepiness during surgery or severely stressful events. In addition, depression is a mental health issue that negatively affects emotional well-being. A group of drugs called anti-depressants is used to treat major depressive illnesses. The aim of the present work was to evaluate the effects of quercetin (QUR) and linalool (LIN) on thiopental sodium (TS)-induced sleeping mice and to investigate the combined effects of these compounds using a conventional co-treatment strategy and in silico studies. For this, the TS-induced sleeping mice were monitored to compare the occurrence, latency, and duration of the sleep-in response to QUR (10, 25, 50 mg/kg), LIN (10, 25, 50 mg/kg), and diazepam (DZP, 3 mg/kg, i.p.). Moreover, an in silico investigation was undertaken to assess this study’s putative modulatory sedation mechanism. For this, we observed the ability of test and standard medications to interact with various gamma-aminobutyric acid A receptor (GABAA) subunits. Results revealed that QUR and LIN cause dose-dependent antidepressant-like and sedative-like effects in animals, respectively. In addition, QUR-50 mg/kg and LIN-50 mg/kg and/or DZP-3 mg/kg combined were associated with an increased latency period and reduced sleeping times in animals. Results of the in silico studies demonstrated that QUR has better binding interaction with GABAA α3, β1, and γ2 subunits when compared with DZP, whereas LIN showed moderate affinity with the GABAA receptor. Taken together, the sleep duration of LIN and DZP is opposed by QUR in TS-induced sleeping mice, suggesting that QUR may be responsible for providing sedation-antagonizing effects through the GABAergic interaction pathway.

Quercetin increases the antidepressant‐like effects of sclareol and antagonizes diazepam in thiopental sodium‐induced sleeping mice: A possible GABAergic transmission intervention

“…The stereochemical characteristics of the predicted models of the GABA protein were confirmed by uploading PDB files to the PDBsum site and having the PROCHECK program examine them. The Phi/Psi Ramachandran plot from the PROCHECK site verified the stereochemical characteristics of the predicted model GABA protein (Bappi, Prottay, Kamli, et al, 2023; Yadav et al, 2013).…”

“…Furthermore, SCL (5, 10, and 15 mg/kg) inhibitory‐like effect on emetic chicks (Bappi, Prottay, Al‐Khafaji, et al, 2023). Several investigations have found that QR (50 and 100 mg/kg) has a strong antidepressant effect in a mouse model (Anjaneyulu et al, 2003; Bappi, Prottay, Kamli, et al, 2023). In addition, DZP (1–3 mg/kg) is often used as a standard treatment for studying sedative, hypnotic, anxiolytic, and other effects on rats and mice (Bappi, Prottay, Kamli, et al, 2023; Iwashita et al, 2023; Meneses et al, 2023).…”

“…Several investigations have found that QR (50 and 100 mg/kg) has a strong antidepressant effect in a mouse model (Anjaneyulu et al, 2003; Bappi, Prottay, Kamli, et al, 2023). In addition, DZP (1–3 mg/kg) is often used as a standard treatment for studying sedative, hypnotic, anxiolytic, and other effects on rats and mice (Bappi, Prottay, Kamli, et al, 2023; Iwashita et al, 2023; Meneses et al, 2023). TS is a barbiturate that is commonly used intravenously to induce general anesthesia fast.…”

“…Briefly, after 0.5 h of the treatments, each animal received TS (20 mg/kg, i.p.) to induce sleep before being put in an observation chamber (e.g., plastic cage) (Bappi, Prottay, Kamli, et al, 2023). After the TS injection, the righting reflex was lost, and the latent period was noted.…”

Anti-inflammatory activity of d-pinitol possibly through inhibiting COX-2 enzyme: in vivo and in silico studies

“…The energy minimization of the ligand structures was performed using the MM2 force field in Chem3D software (version Pro21.0 PerkinElmer Informatics, Inc., Boston, MA, United States) ( Akbor et al, 2023a ). Finally, DPL structure was validated using Lipinski’s rule of five and ADMET analysis in the SwissADME online tool ( Bappi et al, 2023b ). This ensured that the ligands had favorable pharmacological properties and were suitable for molecular docking studies with the prepared protein structures.…”