Pharmacoinformatics based screening discovers swertianolin from Lavandula angustifolia as a novel neuromodulator targeting epilepsy, depression, and anxiety.

• L. augustifolia is a proven anticonvulsant, anxiolytic, and antidepressant plant. • Computational screening was performed for the plant bioactive compounds. • Swertianolin was found to be the potent drug against three target enzymes. • Swertianolin also clears druglikeliness and pharmacokinetic evaluations. In the present study, we evaluate the pharmacological significance of phytoconstituents derived from Lavandula angustifolia with respect to anticonvulsant, antidepressant, and anxiolytic activities using in silico approach against human GABA A R-beta3 receptor, human serotonin transporter, and human potassium channel KCSA-FAB, respectively. Through in silico approach we performed molecular docking simulations, molecular dynamics simulations, binding free energy calculations, and ADMET analysis. In the context, swertianolin, a xanthone heterocyclic compound proved to be an efficient agonist of human GABA A R-beta3 receptor, and inhibitor of both human serotonin transporter, and human potassium channel KCSA-FAB. During molecular docking simulation, swertianolin showed lower binding affinities compared to all the three standard drug controls (methaqualone, paroxetine, and diazepam) used. It also proved its stability to remain in the binding pocket to induce the pharmacological action for extended period of time compared to the standard control drugs. Binding free energy calculations reveal that binding complex of swertianolin was stronger than the respective standard drug controls of the three target proteins. In addition, ADMET analysis of swertianolin predicted zero toxic activity and no negative effect on body metabolism. Therefore, being a site-specific, functionally stable, and null toxic effects on body metabolism, swertianolin could be a better neuromodulator in near future. [ABSTRACT FROM AUTHOR]