Nigella sativa Oil Modulates Neurobehavioral and Neurochemical Alterations in Alcohol-Exposed Rats: An In Vivo and In Silico Study.

Abstract

Background: Chronic alcohol drinking changes central serotonin and dopamine levels, and thereby the functioning of brain circuits that support cognition and anxiety. Previously, it has been proven that Nigella sativa oil (NSO) improves cognition and reduces anxiety by regulating the neurotransmission but the underlying mechanisms are unknown.

Methods: To address the knowledge gap, an in vivo experiment was done to investigate effects of NSO on behavior and neurotransmission in alcohol (ethanol) drinking rats. Specifically, water control, water + NSO treated, ethanol control and ethanol + NSO treated rats were tested for changes in anxiety-like behavior, locomotor activity and learning and memory using the elevated plus-maze test (EPM) and light and dark box (L&D) test, open field test (OFT) and Morris water maze (MWM) test, respectively. Brain neurotransmitter concentrations were determined using HPLC-EC. To validate the in vivo findings, we assessed in silico the docking between NSO compounds and proteins using auto dock vina.

Key findings: Ethanol and NSO reduced weight in the ethanol and ethanol + NSO groups. Food intake, fluid consumption, calorie intake, and growth were similarly affected by ethanol and NSO. In the in vivo experiments, ethanol-treated rats spent less time in the open arms of the EPM and had fewer entries compared to controls, while ethanol + NSO also showed reduced entries. Similar patterns were observed in the OFT. No differences were found in the L&D box test. In the memory tests, ethanol + NSO increased latency in short-term memory, while ethanol increased latency in retention. Neurochemical analysis revealed that ethanol + NSO increased serotonin levels in the PFC and hippocampus while reducing dopamine levels in the PFC compared to all groups, and in the hippocampus compared to control and NSO groups. The in silico experiment revealed that NSO has nine main active compounds. By molecular docking, we found that all nine compounds showed good binding affinity with our target proteins but the best docking values were obtained with thymoquinone and dithymoquinone. The binding affinity estimations identified the superior binding affinity and efficiency of dithymoquinone over all nine NSO compounds for serotonin, dopamine receptors and MAO-enzymes.

Conclusions and significance: NSO partially modulated ethanol-induced neurobehavioral and neurochemical alterations, improving serotonin levels but not fully reversing behavioral deficits. Further studies are needed to explore its protective potential.