Exploring the therapeutic Potential of multi target actions via metformin against Epilepsy through Network Pharmacology

AbstractEpilepsy is a chronic neurological disorder characterized by recurrent seizures and remains amajor global health challenge due to the high prevalence of drug-resistant cases. The present studyemployed a network pharmacology approach to investigate the potential therapeutic mechanisms ofmetformin against epilepsy. Drug targets of metformin were predicted using SwissTargetPrediction,while epilepsy-associated targets were collected from GeneCards, Therapeutic Target Database (TTD),OMIM, and STRING databases. A total of 33 overlapping targets were identified and subjected toprotein–protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopediaof Genes and Genomes (KEGG) pathway enrichment analyses using STRING, Cytoscape, DAVID,and Shiny GO. PPI network analysis identified JAK2 as the major hub protein, followed by JAK1,JAK3, TYK2, PIK3CD, PIK3R2, and PTPN11, indicating their central roles in disease regulation. GOenrichment demonstrated significant involvement in immune signalling, receptor binding, synapticfunction, and inflammatory responses. KEGG pathway analysis revealed significant enrichment of theJAK–STAT, PI3K–Akt, chemokine signalling, and immune-related pathways, suggesting thatmetformin may exert neuroprotective and anti-epileptic effects by modulating neuroinflammation, cellsurvival, and neuronal signalling pathways. These findings indicate that metformin acts through amulti-target, multi-pathway mechanism, with the JAK–STAT signaling pathway emerging as a keytherapeutic target. The study provides a theoretical foundation for further molecular docking andexperimental validation of metformin as a potential therapeutic agent for epilepsy.