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1.
Phytother Res ; 38(5): 2198-2214, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38414297

RESUMEN

Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked. In the FST test, the animals were subjected to forced swimming after 30 min of administration of the test and/or controls for 5 min. In this case, immobility time was measured. In silico studies were conducted to evaluate the involvement of GABA receptors. SCL (5 and 10 mg/kg) significantly increased the latency and decreased sleeping time compared to the control in the TS-induced sleeping time study. DZP (3 mg/kg) showed a sedative-like effect in animals in both sleeping and FST studies. QR (50 mg/kg) exhibited a similar pattern of activity as SCL. However, its effects were more prominent than those of SCL groups. SCL (10 mg/kg) altered the DZP-3-mediated effects. SCL-10 co-treated with QR-50 significantly (p < 0.05) increased the latency and decreased sleep time and immobility time, suggesting possible synergistic antidepressant-like effects. In silico studies revealed that SCL and QR demonstrated better binding affinities with GABAA receptor, especially α2, α3, and α5 subunits. Both compounds also exhibited good ADMET and drug-like properties. In animal studies, the both compounds worked synergistically to provide antidepressant-like effects in a slightly different fashion. As a conclusion, the combined administration of SCL and QR may be used in upcoming neurological clinical trials, according to in vivo and in silico findings. However, additional investigation is necessary to verify this behavior and clarify the potential mechanism of action.


Asunto(s)
Antidepresivos , Diazepam , Quercetina , Sueño , Tiopental , Animales , Ratones , Antidepresivos/farmacología , Masculino , Quercetina/farmacología , Diazepam/farmacología , Sueño/efectos de los fármacos , Tiopental/farmacología , Natación , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Hipnóticos y Sedantes/farmacología , Receptores de GABA-A/metabolismo
2.
Molecules ; 28(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37513487

RESUMEN

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, ß1, 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.


Asunto(s)
Trastorno Depresivo Mayor , Hipnóticos y Sedantes , Ratones , Animales , Hipnóticos y Sedantes/farmacología , Quercetina/farmacología , Receptores de GABA-A/metabolismo , Ácido gamma-Aminobutírico
3.
Biology (Basel) ; 12(5)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37237451

RESUMEN

Frequent use of various food processing chemical agents sometimes causes damage to our bodies by inducing cytotoxicity, genotoxicity, and mutagenesis. In Bangladesh, among various chemical agents, formalin, saccharin, and urea are vastly used for processing foodstuffs by industry and local people. This study is focused to assess the toxic effects of formalin, saccharin, and urea on the popularly used eukaryotic test model, Allium cepa L. The assay was carried out by exposing different concentrations of test samples to A. cepa at 24, 48, and 72 h, where distilled water and CuSO4·5H2O (0.6 µg/mL) were utilized as the vehicle and positive control, respectively. The root length of the onions was measured in mm, and the results propose that all the chemical agents demonstrated toxicity in onions in a concentration- and exposure-time-dependent manner. The highest root length was examined at the lower concentrations, and with the increase in the concentration of the test sample and exposure time, the RG (root growth) was inhibited due to the deposition of chemicals and hampering of cell division in the root meristematic region of A. cepa. All the chemical agents also revealed a concentration- and time-dependent adaptive effect up to 72 h inspection of 24 h and a depletion of % root growth at 72 h inspection of 48 h. Our study suggests that sufficient precautions should be confirmed during its industrial and traditional usage as a toxicological response to the chemical agents observed in the A. cepa assay.

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