Nigella sativa Oil Improves Motor Skill Learning of Albino Mice: In Vivo and In Silico Investigations

Experimental evidences demonstrated that Nigella sativa oil (NSO) can restore neuronal integrities and processes by increasing the neuronal density, decreasing apoptosis, preventing inflammatory processes, and improving the neurogenic cells in the hippocampus. This refurbishment enhances the learning process and memory. The antioxidant defense mechanism of NSO slows down the process of neurodegeneration and motor deficit. The present study aimed to investigate the effects of NSO on motor skill learning using the single pellet reaching task method on Swiss albino mice, followed by in silico studies. Mice (total of 16) were randomly divided into the control group and treatment group (n = 8). The treatment group received 1 ml/kg b.w. NSO orally once daily for 7 days, and a control group received 1 ml/kg normal saline instead of NSO in a similar manner. The average success rate due to ingestion of NSO in the treatment group mice increased significantly (P < 0.05) compared to controlled mice. Molecular docking analysis revealed that thymoquinone, carvacrol, thymohydroquinone, p-cymene, and t-anethole have binding affinities for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) that ranges from (-5.1 to -6.2) kcal/mol, which is comparable to the reference ligand glutamic acid binding affinity with AMPA-R (-6.6 kcal/mol). Thymoquinone and carvacrol formed hydrogen bonds with AMPA receptor at TYR61, SER142, and SER143 residues, comparable to the binding affinity of glutamic acid. ADMET analysis reported that all the compounds have higher bioavailability (>90%) and can cross the BBB easily (logBB> 0.3). Based on our experimental data and in silico report, we concluded that the enhanced motor skill learning effects of NSO are due to presence of potent antioxidants—thymoquinone and carvacrol—which might serve as AMPA receptor agonists. These phytoconstituents may play role in synaptic strengthening and promote experience-dependent motor skill learning.