Integrative evaluation of Daucus carota L. as an antiepileptic agent: In silico (network pharmacology, ADMET, molecular docking, MD Simulation) and in vivo correlation using PTZ-induced seizure model
Naznin Sarkar, Anil Kumar Venkategowda Kodihally, Mahasin Khan · In Silico Research in Biomedicine · 2025
Epilepsy is a chronic neurological disorder that often requires long-term medication, leading to adverse effects and drug resistance. This study investigated the antiepileptic potential of Daucus carota L. (carrot) root extract through an integrative in silico and in vivo approach. The ethanolic extract was analyzed using LC–MS, identifying twenty-four bioactive constituents. These compounds were evaluated for drug-likeness and ADMET profiles, which indicated favorable pharmacokinetic and safety properties. Network pharmacology revealed 192 potential targets, with 54 associated with epilepsy, emphasizing GABRA1 and CACNA1H as key targets involved in GABAergic and calcium channel modulation. Molecular docking and MM-GBSA binding energy analyses demonstrated strong binding affinities of major compounds such as luteolin, apigenin, and retinol with these targets. The molecular dynamics simulations further confirmed the stability of these protein–ligand complexes, supporting their predicted interactions and mechanism of action. In vivo evaluation using the Pentylenetetrazole (PTZ) induced seizure model in Swiss albino mice showed significant, dose-dependent anticonvulsant effects, with the higher dose providing protection comparable to ethosuximide. Combination therapy further enhanced seizure protection without toxicity. Collectively, this integrative study combining phytochemical profiling, computational modeling (docking, MM-GBSA, and MD simulation), and preclinical validation establishes Daucus carota as a promising, multi-targeted natural anticonvulsant candidate with potential therapeutic relevance.