(A) Docking study of embelin with respect to diazepam and the GABAA receptor. (B) Proposed mechanism of action of embelin at the GABAA receptor to reverse PTZ induced seizures. 8B1—During a seizure, a prolonged opening of the voltage-gated Na+ channel causes an influx of sodium ions which leads to depolarization and repetitive neuronal firing. The opening of Ca2+ channels increases the influx of positive calcium ions causing prolonged spikes and T current waves. As there is no affinity for the GABAA receptor, the decreased Cl− influx causes epileptic excitation inside the neuron cell. 8B2—EMB shows higher affinity for GABAA receptor binding; it facilitates GABA mediated Cl− channel opening with cell hyperpolarization and reduced seizure frequency, prolonged inactivation of the voltage-gated neuronal Na+ channel, prevented intracellular Na+ accumulation, reduced Ca2+ influx, and inhibited glutamate.
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