Exploring the Antiepileptic Potential of Puerarin in a PTZ‐Induced Epilepsy Model Using Combined In Vivo and In Silico Approaches

ABSTRACT Seizure is a neurological disorder characterized by the abnormal discharge of electricity in some or all of the brain, leading to motor, sensory, or psychomotor abnormalities. In the present study, the Antiepileptic effect of the puerarin flavonoids was evaluated against the PTZ‐induced seizure in animals. The puerarin administration evidently increased the duration of seizure onset as compared to the only PTZ‐treated group. Similarly, administration of the puerarin dose dependently reduced the seizure duration and seizure severity using the Racine scale; however, the maximum dose produced a pronounced Antiepileptic effect. Following in vivo activities, computational studies were conducted to assess the mechanism and dynamic stability of the complexes. The molecular docking analysis showed maximum binding energies of the puerarin with the 2OKK and 2W8O target proteins and interactions via multiple hydrogen and hydrophobic bonds. Following the docking analysis, molecular dynamic (MD) simulations were performed, and post‐MD analysis showed that all complexes remained stable during the entire 100 ns simulation. The MD analysis was followed by Molecular Mechanics–Poisson–Boltzmann Surface Area and Molecular Mechanics–Generalized Born Surface Area (MM‐PBSA, MM‐GBSA) calculations for both complexes, that is, 2OKK and 2W8O. The results showed the energy of the system remains negative, and favorable bonding interactions have been observed in both ligand‐protein systems.