Antiepileptic potential ofJacq. extracts: an exploratory study integrating in vivo seizure models and computational analysis.

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from abnormal neuronal excitability and ion channel dysfunction. This study explored the antiepileptic potential ofusing integrated in vivo and in silico approaches to identify safer alternatives to conventional therapies. Ethanolic extracts of the plant were fractionated into petroleum ether (PE) and ethyl acetate (EA) fractions and analyzed via LC-MS for tentative phytoconstituent identification. Anticonvulsant activity of both fractions was evaluated in Swiss albino mice using pentylenetetrazol (PTZ) and maximal electroshock seizure (MES) models. The PE fraction significantly reduced seizure frequency, duration, and mortality (< 0.05), demonstrating effects comparable to diazepam. Molecular docking and MM/GBSA analyses revealed strong binding affinities of major compounds toward GABAA and Nav1.2 receptors. Notably, (-)-jatrointelignan A (C&#x2083;&#x2081;H&#x2083;&#x2086;O&#x2081;&#x2081;) exhibited the highest docking scores (-10.20 kcal/mol for GABAA and -11.47 kcal/mol for Nav1.2) and favorable binding free energies (-25.38 and -70.63 kcal/mol, respectively). ADME and toxicity predictions suggested good pharmacokinetic properties with low toxicity, while molecular dynamics simulations confirmed stable receptor ligand interactions. Overall,and its lead compound demonstrate promising antiepileptic potential via dual modulation of GABAergic and sodium channel pathways.