article · Phytotherapy Research
This research evaluated the combined and separate effects of the natural compounds quercetin and sclareol on central nervous system responses in mice. Using thiopental sodium-induced sleep and forced swimming tests, sedation and antidepressant-like behaviours were assessed alongside computational modelling of GABAA receptors. Administering sclareol reduced sleeping duration and increased sleep latency, counteracting the sedative actions of diazepam. Quercetin demonstrated similar but more pronounced responses. When co-administered, sclareol and quercetin acted synergistically, significantly extending sleep latency while reducing total sleeping duration and immobility time in forced swimming tests. Computational analyses indicated that both compounds exhibit favourable drug-like properties and strong binding affinities towards specific GABAA receptor subunits, notably alpha 2, alpha 3, and alpha 5. These findings demonstrate that the combination produces synergistic antidepressant-like outcomes through potential GABAergic pathway interactions.
Depression and related central nervous system conditions present substantial clinical challenges, driving interest in plant-derived treatments. Demonstrating that combining quercetin with sclareol generates synergistic antidepressant-like effects while counteracting sedative actions offers valuable insight into alternative therapies. Because both compounds display favourable drug-like properties in early evaluations, the findings suggest a promising route for developing multi-compound neurological formulations targeting GABAergic transmission.
This work points towards potential applications in pharmaceutical formulation for depressive and neurological disorders. Prospective users include drug development teams and clinical researchers investigating plant-derived synergistic compounds. The technology is at an early research stage, having been validated solely in laboratory mouse models and computational simulations. Substantial further laboratory investigation and clinical trials will be necessary before any real-world commercial therapy can be realised.
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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 α<sub>2</sub>, α<sub>3</sub>, and α<sub>5</sub> 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.
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DOI: 10.1002/ptr.8139
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