Studies on the anticonvulsant potential of 6-gingerol, an active ingredient of ginger rhizome

Ginger (Zingiber officinale), due to its diverse therapeutic properties, continues to attract researchers' attention. One of these properties is its anticonvulsant activity, which, as our previous studies have shown, may result from the presence of 6-gingerol, a compound that reduced pentylenetetrazole (PTZ)-induced hyperlocomotion in zebrafish larvae. In the present study, we further investigated the anticonvulsant effects of 6-gingerol using additional seizure and epilepsy models in both zebrafish larvae and mice. First, we observed that 6-gingerol reduced the overexpression of the neuronal PAS domain protein (npas4) gene in PTZ-exposed zebrafish larvae, but it did not affect the expression of brain-derived neurotrophic factor (bdnf). The anticonvulsant effect of 6-gingerol was evident in the ethyl 2-ketopent-4-enoate seizure test in zebrafish larvae but was not observed in the pilocarpine model or in scn1lab (Dravet syndrome model) and cacna1aa (absence seizure model) zebrafish morphants. In mice, 6-gingerol penetrated the blood-brain barrier and inhibited psychomotor seizures induced by 6 Hz electrical stimulation at an intensity of 32 mA, but it was ineffective at 44 mA. We did not observe any anticonvulsant effects of 6-gingerol in the maximal electroshock test or timed intravenous PTZ infusion seizure test in mice. In summary, our findings provide further evidence for the anticonvulsant effects of 6-gingerol; however, additional investigations are required to clarify its mechanisms of action.