In-silico investigation of the therapeutic potentials and activities of certain plants used in the management of epilepsy

Abstract

Epilepsy stands out as one of the prevalent and severe brain disorders. Traditional medicinal plants have been used as remedies for epilepsy in various cultures. By utilizing natural lead compounds identified through virtual screening and pharmacokinetic prediction, it becomes feasible to develop effective molecules for the management of epilepsy. This study aims to evaluate the anti-epileptic potentials of phytoconstituents present in Caesalpnie bonduc, Origanum majorana, and Annona squamosa using in-silico methods. Phytoconstituents of these plants were obtained in their SDF files from the PubChem database and prepared using the ligprep panel in Maestro 12.8; the proteins, GABA Receptor, GABA Reuptake Transporter 1 Receptor (7SK2) and Human Na-K-2cl Co-transporter Isoform 1 (7S1X) were retrieved from protein data bank, prepared utilizing the protein preparation wizard, followed by receptor grid generation to define active sites for docking. Molecular docking was performed using high throughput virtual screening in the maestro software while Swiss ADME and Protox II were used to assess the pharmacokinetic and toxicity properties of test compounds respectively.
This study revealed that 8 phytoconstituents from C. bonduc had higher binding affinity than the standard molecule diazepam against the GABA receptor protein, up to 45 exhibited higher binding affinity than tiagabine against the GAT receptor while 4 compounds were seen to have higher affinity than bumetanide against the Human NKCC receptor. 20 phytoconstituents from O. majorana were observed to have higher binding affinity than the standard against GAT, 22 compounds had higher binding affinity than diazepam against the GABA receptor while 4 compounds had higher scores than the Human NKCC standard. 8 phytoconstituents from A. squamosa had higher binding affinity than the standard molecule diazepam, 6 compounds had higher binding affinity than tiagabine while 4 compounds with comparative docking affinities as the standard against Human NKCC were selected together with the other compounds from the other target proteins for further screening. ADMET analysis revealed favorable pharmacokinetic and toxicity properties while post-docking analysis showed the molecular interactions of ligands with the receptors. In-silico studies of the various plant phytoconstituents provide considerable leads for further drug development and lead optimization valuable to the discovery of more efficacious drugs for the management of epilepsy.