Pharmacological Potential Of Pinosylvin In Ptz Induced Epilipsy

Abstract

Epilepsy is a chronic neurological disorder characterized by recurrent seizures and is frequently associated with neuroinflammation, oxidative stress, and behavioral impairments. Despite the availability of several antiepileptic drugs, treatment resistance and adverse effects remain major clinical challenges, highlighting the need for safer and more effective therapeutic alternatives. The present study investigated the anticonvulsant and neuroprotective potential of pinosylvin, a naturally occurring stilbenoid polyphenol, in a pentylenetetrazole (PTZ)-induced epilepsy model using integrated in silico and in vivo approaches. Pharmacokinetic profiling was performed using the pkCSM platform, while molecular docking analysis evaluated interactions with epilepsy-related targets, including γ-aminobutyric acid (GABA) receptors and nuclear factor-kappa B (NF-κB). In vivo experiments were conducted in PTZ-treated mice, followed by behavioral assessment using the Elevated Plus Maze (EPM) and evaluation of neuroinflammatory gene expression through quantitative real-time polymerase chain reaction (qRT-PCR). ADMET analysis demonstrated favorable pharmacokinetic properties, including high intestinal absorption, satisfactory blood-brain barrier permeability, and low predicted toxicity. Molecular docking revealed strong binding affinities of pinosylvin toward GABA receptors (−6.1 kcal/mol) and NF-κB (−6.6 kcal/mol), suggesting potential modulation of inhibitory neurotransmission and inflammatory pathways. Behavioral findings showed that pinosylvin significantly alleviated PTZ-induced anxiety-like behavior by increasing open-arm exploration and reducing closed-arm occupancy. Furthermore, qRT-PCR analysis demonstrated significant downregulation of NF-κB and NLRP3 gene expression compared with the PTZ-treated group, indicating attenuation of seizure-associated neuroinflammation. Collectively, these findings suggest that pinosylvin exerts significant anticonvulsant, anxiolytic, and anti-inflammatory effects, potentially through modulation of GABAergic signaling and suppression of the NF-κB/NLRP3 inflammatory axis. Therefore, pinosylvin may represent a promising natural therapeutic candidate for epilepsy management and warrants further preclinical and clinical investigation.