(+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice.
(+)-Dehydrofukinone (DHF), isolated from Nectandra grandiflora (Lauraceae) essential oil, induces sedation and anesthesia by modulation of GABAa receptors. However, no study has addressed whether DHF modulates other cellular events involved in the control of cellular excitability, such as seizure behavior. Therefore, the aim of the present study was to investigate the effect of DHF on cellular excitability and seizure behavior in mice. For this purpose, we used isolated nerve terminals (synaptosomes) to examine the effect of DHF on the plasma membrane potential, the involvement of GABAa receptors and the downstream activation of Ca2+ mobilization. Finally, we performed an in vivo assay in order to verify whether DHF could impact on seizures induced by pentylenetetrazole (PTZ) in mice. The results showed that DHF induced a GABA-dependent sustained hyperpolarization, sensitive to flumazenil and absent in low-[Cl-] medium. Additionally, (1-100μM) DHF decreased KCl-evoked calcium mobilization over time in a concentration-dependent manner and this effect was prevented by flumazenil. DHF increased the latency to myoclonic jerks (10mg/kg), delayed the onset of generalized tonic-clonic seizures (10, 30 and 100mg/kg), and these effects were also blocked by the pretreatment with flumazenil. Our data indicate that DHF has anticonvulsant properties and the molecular target underlying this effect is likely to be the facilitation of GABAergic neuronal inhibition. The present study highlights the therapeutic potential of the natural compound DHF as a suppressor of neuronal excitability.
['Garlet|Quelen Iane|QI|', 'Pires|Luana da Costa|LDC|', 'Milanesi|Laura Hautrive|LH|', 'Marafiga|Joseane Righes|JR|', 'Baldisserotto|Bernardo|B|', 'Mello|Carlos Fernando|CF|', 'Heinzmann|Berta Maria|BM|']
D000818:Animals D000927:Anticonvulsants D005260:Female D005442:Flumazenil D018757:GABA Modulators D008564:Membrane Potentials D051379:Mice D010433:Pentylenetetrazole D011963:Receptors, GABA-A D012640:Seizures D012717:Sesquiterpenes
Nectandra grandiflora Essential oil Calcium Anticonvulsant Natural products