Abstract
The current study aimed to explore the anxiolytic effects of phytochemicals present in Nigella sativa (black cumin) plant seeds. For that purpose, first we identified a plethora of bioactive phytocompounds by performing gas chromatography and mass spectrometry (GC-MS) analysis. GC-MS results revealed a total of 38 phytochemicals, including Guanosine 29.80%, Ethanamine 13.25%, Valeric acid, 2-tridecyl ester 12.48%, Pentanal 7.34%, 1-Dodecanol 5.65%, as the most abundant compounds, which represent 68% of the total chromatographic composition. The identified phytochemicals (ligands) from GCMS were subjected to molecular docking against the GABA-B (target protein) to screen top phytochemicals based on their docking scores. The docking results exhibited a range from - 2.5 (Ethanamine) to - 7.9 kcal/mol (Androstan-3-one). Furthermore, based on docking scores, the top six selected compounds, namely kasuminl, thunbergol, dehydro-cohumulinic acid, jasmoline, androstan-3-one, and hydrothymoquinone, were further checked for different pharmacological parameters such as ADME/T, biological activity, Lipinski's analysis, and physicochemical properties such as solubility (logS), lipophilicity (logP) and Total Polar Surface Area (tPSA). Moreover, molecular dynamics (MD) simulation trajectories such as RMSD, RMSF, Rg and SASA showed excellent dynamic behaviour, including structural stability, conformational flexibility and spatial organization over time. Overall, hydrothymoquinone, dehydro-cohumulinic acid, and androstan-3-one show great stability and favourable binding affinity against GABA-B. The collective results obtained from this study suggest that these natural phytochemicals derived from N. sativa may serve as lead compounds for anxiolytic effects. However, in-vitro and in-vivo studies are recommended to further validate their efficacy and establish them as drug candidates.