Investigating the anxiolytic potential of Withania somnifera: a GC–MS and in silico study targeting MAO-A inhibition

The current study aimed to conduct a phytochemical screening of commonly known Withania somnifera leaf extract through gas chromatography and mass spectrometry (GC–MS) to identify the bioactive compounds responsible for its MAO-A inhibitory action and evaluate the pharmacological potentialities of the extract and its fractions against anxiety. In the in-silico analysis, various tools were employed, including molecular docking and molecular dynamics (MD) simulation. These methods assessed the binding affinity and stability of the phytochemicals (ligands) with MAO-A. The preclinical efficacy and safety of the phytochemicals were evaluated using ADMET/T analysis. Furthermore, the biological activity of the selected phytochemicals as potential “MAO-A” inhibitors was assessed using PASS analysis. Lipinski’s rule of five was applied to predict the drug-likeness properties of the compounds. The interacting residues and the types of interactions between the active site of MAO-A and the compounds were evaluated. The cumulative results of these analyses identified 2-Methoxy-4-vinylphenol, Hexadecanoic acid, N,N-Bis(2-hydroxyethyl) dodecanamide, 1,2 Benzene dicarboxylic acid diethyl ester, and Oxacycloheptadec-8-en-2-one as hit compounds from W. somnifera, suggesting their potential as MAO-A inhibitors. This research aims to provide an elaborative description of promising phytochemical entities with activities against MAO-A. However, the efficacy of these phytochemicals as potential anxiolytic compounds needs further validation via in vitro and in vivo studies.