Abstract
Oxidative stress is known to be associated with epilepsy, and antiseizure medication treatment, albeit with limited consensus on the specific oxidative stress pathways/proteins involved. Identifying these can reveal novel therapeutic targets for epilepsy management. This study utilized network pharmacology to identify potential protein targets of carbamazepine and valproic-acid that are implicated in oxidative stress and epilepsy, thereby highlighting their therapeutic potential. Drug targets for carbamazepine and valproic-acid were predicted using SuperPred/SwissTargetPrediction, while genes associated with epilepsy and oxidative stress were obtained from DisGeNET and GeneCards. Common proteins were identified, and a protein-protein interaction network was constructed using STRING, followed by analysis via Cytoscape. Hub proteins identified were EGFR, GSK3B, and STAT3 for carbamazepine, and PTGS2, mTOR, and TLR4 for valproic-acid. Molecular docking revealed a strong binding affinity of carbamazepine to its targets (ΔG(bind) > - 5 kcal/mol) and binding of valproic-acid to its targets (ΔG(bind) > - 3 kcal/mol), with PTGS2 showing the strongest interaction with valproic-acid (- 5.06 kcal/mol). These findings underscore EGFR, GSK3B, and STAT3, for carbamazepine and PTGS2, mTOR, and TLR4 for valproic-acid as pivotal therapeutic targets in oxidative stress-associated epilepsy. These identified proteins can be targeted by add on antioxidants to alleviate oxidative stress generated by chronic antiseizure medication.