Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway
Abstract
:1. Introduction
2. Results
2.1. In Vivo Study
2.2. In Silico Study
2.2.1. GABA Homology Model
Interaction of QUR with GABAA Receptor Subunits
Interaction of LIN with GABAA Receptor Subunits
Interaction of DZP with GABAA Receptor Subunits
2.2.2. Pharmacokinetics and Drug-Likeness Properties
3. Discussion
4. Materials and Methods
4.1. In Vivo Study
4.1.1. Chemicals and Reagents
4.1.2. Experimental Animals
4.1.3. Selection of Test Doses for Quercetin and Linalool
4.1.4. Study Design (Thiopental Sodium-Induced Slee** Test in Mice)
4.1.5. Statistical Analysis
4.2. Molecular Docking (In Silico) Study
4.2.1. GABA Homology Model
Retrieval of Sequence
Model Building and Evaluation
4.2.2. Protein Preparation
4.2.3. Ligand Preparation
4.2.4. Docking Protocol and Non-Bond Interactions
4.2.5. Pharmacokinetics and Drug-Likeness Properties
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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First Squad | |||
---|---|---|---|
Treatment Group | Latency (min) | Slee** Time (min) | Sleep Incidence (%) |
Gr-I | 5.40 ± 0.84 | 41.20 ± 5.02 | 100 |
Gr-II | 3.20 ± 0.65 * | 99.60 ± 5.73 * | 100 |
Gr-III | 29.40 ± 2.08 | 12.40 ± 2.21 | 100 |
Gr-IV | 42.60 ± 2.01 | 15.60 ± 1.23 | 100 |
Gr-V | 53.40 ± 2.56 | 24.00 ± 5.24 | 100 |
Gr-VI | 5.80 ± 0.73 | 44.60 ± 2.01 * | 100 |
Gr-VII | 6.80 ± 0.97 | 46.40 ± 2.01 * | 100 |
Gr-VIII | 8.40 ± 0.76 | 53.20 ± 4.04 * | 100 |
Second Squad | |||
---|---|---|---|
Treatment Group | Latency (min) | Slee** Time (min) | Sleep Incidence (%) |
Gr-CI * | 5.40 ± 0.84 | 41.20 ± 5.02 | 100 |
Gr-CII a | 53.40 ± 2.56 | 24.00 ± 5.24 | 100 |
Gr-CIII b | 8.40 ± 0.76 a | 53.20 ± 4.04 *a | 100 |
Gr-CIV | 3.20 ± 0.65 *ab | 99.60 ± 5.73 *ab | 100 |
Gr-CV | 16.80 ± 2.43 a | 34.00 ± 5.46 a | 100 |
Gr-CVI | 43.00 ± 4.15 a | 46.20 ± 1.30 *a | 100 |
Treatment Group | Latency Decrease (%) | Slee** Time Increase (%) |
---|---|---|
Gr-CII | - | - |
Gr-CIII | - | 22.56 |
Gr-CIV | 92.23 | 58.63 |
Gr-CV | - | - |
Gr-CVI | - | 10.82 |
Protein (Receptor) | Binding Affinity (Kcal/mol) | Number of Hydrogen Bond | Number of Hydrophobic Bond | Number of Others Bond |
---|---|---|---|---|
GABAA α1 | −7.1 | 2 | 4 | - |
GABAA α2 | −7.9 | 5 | 5 | 1 |
GABAA α3 | −8.2 | 2 | 5 | - |
GABAA α5 | −7.5 | 2 | 2 | 1 |
GABAA β1 | −8.0 | 4 | 4 | - |
GABAA β2 | −7.8 | 4 | 2 | - |
GABAA β3 | −7.0 | 5 | 2 | - |
GABAA γ2 | −7.0 | 4 | 3 | - |
Protein (Receptor) | Binding Affinity (Kcal/mol) | Number of Hydrogen Bond | Number of Hydrophobic Bond | Number of Others Bond |
---|---|---|---|---|
GABAA α1 | −4.8 | 1 | 11 | - |
GABAA α2 | −4.5 | - | 6 | - |
GABAA α3 | −5.2 | 1 | 9 | - |
GABAA α5 | −4.8 | 1 | 7 | - |
GABAA β1 | −5.8 | - | 12 | - |
GABAA β2 | −4.8 | 1 | 6 | - |
GABAA β3 | −4.8 | 1 | 6 | - |
GABAA γ2 | −4.3 | - | 7 | - |
Protein (Receptor) | Binding Affinity (Kcal/mol) | Number of Hydrogen Bond | Number of Hydrophobic Bond | Number of Others Bond |
---|---|---|---|---|
GABAA α1 | −6.4 | 1 | 7 | 1 |
GABAA α2 | −6.7 | 1 | 7 | 1 |
GABAA α3 | −6.8 | - | 9 | - |
GABAA α5 | −6.5 | 3 | 4 | 3 |
GABAA β1 | −7.8 | 1 | 6 | - |
GABAA β2 | −7.0 | 2 | 2 | 2 |
GABAA β3 | −6.3 | 2 | 2 | - |
GABAA γ2 | −7.7 | 5 | 2 | - |
Properties | Factors | Quercetin | Linalool | Diazepam |
---|---|---|---|---|
Physico-chemical properties | Formula | C15H10O7 | C10H18O | C16H13ClN2O |
MW (g mol−1) | 302.24 | 154.25 | 284.74 | |
Heavy atoms | 22 | 11 | 20 | |
Arom. heavy atoms | 16 | 0 | 12 | |
H-Bond acceptors (HBAs) | 7 | 1 | 2 | |
H-Bond donors (HBDs) | 5 | 1 | 0 | |
Molar refractivity | 78.03 | 50.44 | 87.95 | |
TPSA (Å2) | 131.36 | 20.23 | 32.67 | |
Lipophilicity | log Po/w (XLOGP3) | 1.54 | 2.97 | 2.99 |
Water solubility | log S (ESOL) | Soluble | Soluble | Soluble |
Pharmacokinetics | GI absorption | High | High | High |
Drug likeness | Lipinski | Yes | Yes | Yes |
Bioavailability score | 0.55 | 0.55 | 0.55 | |
Medicinal chemistry | Synthetic accessibility | 3.23 | 2.74 | 3.00 |
First Squad | ||
---|---|---|
Treatments | Composition | Dose |
Gr-I | Vehicle (0.5% tween 80 dissolved in normal saline) | 10 mL/kg |
Gr-II | Diazepam (DZP) | 3 mg/kg |
Gr-III | Quercetin (QUR) | 10 mg/kg |
Gr-IV | QUR | 25 mg/kg |
Gr-V | QUR | 50 mg/kg |
Gr-VI | Linalool (LIN) | 10 mg/kg |
Gr-VI | LIN | 25 mg/kg |
Gr-VI | LIN | 50 mg/kg |
Second squad | ||
Treatments | Composition | Dose |
Gr-CI | Vehicle | 10 mL/kg |
Gr-CII | QUR | 50 mg/kg |
Gr-CIII | LIN | 50 mg/kg |
Gr-CIV | DZP | 3 mg/kg |
Gr-CV | QUR-50 + LIN-50 | 50 mg/kg + 50 mg/kg |
Gr-CVI | QUR-50 + DZP-3 + LIN-50 | 50 mg/kg + 3 mg/kg + 50 mg/kg |
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Bappi, M.H.; Prottay, A.A.S.; Kamli, H.; Sonia, F.A.; Mia, M.N.; Akbor, M.S.; Hossen, M.M.; Awadallah, S.; Mubarak, M.S.; Islam, M.T. Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway. Molecules 2023, 28, 5616. https://doi.org/10.3390/molecules28145616
Bappi MH, Prottay AAS, Kamli H, Sonia FA, Mia MN, Akbor MS, Hossen MM, Awadallah S, Mubarak MS, Islam MT. Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway. Molecules. 2023; 28(14):5616. https://doi.org/10.3390/molecules28145616
Chicago/Turabian StyleBappi, Mehedi Hasan, Abdullah Al Shamsh Prottay, Hossam Kamli, Fatema Akter Sonia, Md. Nayem Mia, Md. Showkoth Akbor, Md. Munnaf Hossen, Samir Awadallah, Mohammad S. Mubarak, and Muhammad Torequl Islam. 2023. "Quercetin Antagonizes the Sedative Effects of Linalool, Possibly through the GABAergic Interaction Pathway" Molecules 28, no. 14: 5616. https://doi.org/10.3390/molecules28145616