TY - JOUR
T1 - Quercetin and/or ascorbic acid modulatory effect on phenobarbital-induced sleeping mice possibly through gabaa and gabab receptor interaction pathway
AU - Hossain, Rajib
AU - Al-Khafaji, Khattab
AU - Khan, Rasel Ahmed
AU - Sarkar, Chandan
AU - Islam, Md D. Shahazul
AU - Dey, Dipta
AU - Jain, Divya
AU - Faria, Farhana
AU - Akbor, Rukaya
AU - Atolani, Olubunmi
AU - Oliveira, Sónia M.R.
AU - Siyadatpanah, Abolghasem
AU - Pereira, Maria de Lourdes
AU - Islam, Muhammad Torequl
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/7/26
Y1 - 2021/7/26
N2 - Background: Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. Objectives: This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. Methods: QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Results: Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Conclusions: Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.
AB - Background: Depressive disorder is a recurrent illness that affects large numbers of the general population worldwide. In recent years, the goal of depression treatment has moved from symptomatic response to that of full remission. However, treatment-resistant depression is a major challenge in the treatment of depression or depression-related disorders. Consensus opinion, therefore, suggests that effective combined aggressive initial treatment is the most appropriate strategy. Objectives: This study aimed to evaluate the effects of quercetin (QUR) and/or ascorbic acid (AA) on Phenobarbital-induced sleeping mice. Methods: QUR (50 mg/kg) and/or AA (25 mg/kg) with or without intraperitoneally pre-treated with GABA receptor agonist (diazepam: 2 mg/kg, i.p.) or antagonist (Flumazenil: 2.5 mg/kg, i.p.) to underscore the effects, as well as the possible involvement of the GABA receptor in the modulatory action of QUR and AA in sleeping mice. Additionally, an in silico study was undertaken to predict the involvement of GABA receptors in the sleep mechanism. Results: Findings suggest that the pretreatment of QUR and AA modulated the onset and duration of action of the standard drugs in experimental animals. The acute administration of QUR and/or AA significantly (p < 0.05) reversed the DZP-mediated onset of action and slightly reversed the duration of sleep time in comparison to the vehicle (control) group. A further combination of QUR or AA with the FLU resulted in an enhancement of the onset of action while reducing the duration of action, suggesting a FLU-like effect on the test animals. In in silico studies, AA and QUR showed good to moderate binding affinities with GABAA and GABAB receptors. Conclusions: Both QUR and AA produced a stimulatory-like effect on mice, possibly through the GABAA and GABAB receptor interaction pathways. Further studies are necessary to verify this activity and clarify the exact mechanism of action(s) involved.
KW - Ascorbic acid
KW - GABA receptor
KW - Molecular docking
KW - Mus musculus
KW - Quercetin
KW - Stimulatory-like activity
UR - http://www.scopus.com/inward/record.url?scp=85112001153&partnerID=8YFLogxK
U2 - 10.3390/ph14080721
DO - 10.3390/ph14080721
M3 - Article
C2 - 34451819
AN - SCOPUS:85112001153
SN - 1424-8247
VL - 14
SP - 1
EP - 22
JO - Pharmaceuticals
JF - Pharmaceuticals
IS - 8
M1 - 721
ER -