RESUMO
BACKGROUND: Sleep and stress interact bidirectionally by acting on brain circuits that affect metabolism. Sleep and its alterations have impact on blood leptin levels, metabolic hormone that regulates appetite. Brain expresses the receptors for the peptide hormone leptin produced from adipocytes. The hypothalamic orexin neurons are low during sleep and active when awake, influenced by a complex interaction with leptin. Thymoquinone was found to be the major bioactive component of Nigella sativa. The aim of this study was to study the role of thymoquinone on sleep restriction and its mitigating effect on leptin-mediated signaling pathway in rat brain. METHODS AND RESULTS: 30 adult male Wistar rats were divided into 5 groups with 6 animals in each group: Control; Thymoquinone (TQ); Corn oil; Chronic Sleep restriction (CSR); and CSR + TQ. After 30 days, behavioral analysis, antioxidant, lipid profile, glucose level, liver and kidney function test, neurotransmitters, neuropeptides, and mRNA expression in in vivo studies were also assessed and pharmacokinetic and docking were done for thymoquinone. Thymoquinone has also shown good binding affinity to the target proteins. CSR has induced oxidative stress in the discrete brain regions and plasma. Current study has shown many evidences that sleep restriction has altered the neurobehavioral, antioxidant status, lipid profile, neurotransmitters, neuropeptide levels, and feeding behavior which damage the Orexin-leptin system which regulates the sleep and feeding that leads to metabolic dysfunction. CONCLUSION: The potentiality of Thymoquinone was revealed in in silico studies, and its action in in vivo studies has proved its effectiveness. The study concludes that Thymoquinone has exhibited its effect by diminishing the metabolic dysfunction by its neuroprotective, antioxidant, and hypolipidemic properties.
