Anticonvulsant activity of essential oil from leaves of Zhumeria majdae (Rech.) in mice: The role of GABAA neurotransmission and nitric oxide pathway.

The essential oil from leaves of Zhumeria majdae Rech. (ZMEO), had been shown to have several beneficial effects in clinic. Here, we examined anticonvulsant activities of ZMEO in experimental mouse model of seizure and tried to identify possible underlying mechanisms. ZMEO (5, 10, 20 and 40 mg kg-1, IP) or diazepam, as reference anti-convulsant drug (25, 50 and 100 µg kg-1, IP), were administered 60 min prior to PTZ injection (IV or IP) and changes in threshold, latency and frequency of clonic seizure were examined. I.P PTZ induced model of seizure was also applied for examining protective effects of ZMEO pretreatment against PTZ induced mortality. In some studies, the anti-convulsant effect of the combination of diazepam and ZMEO was also studied. Protective effects of ZMEO against hind-limb tonic extensions (HLTE) was also examined by maximal electroshock (MES) seizure test. The GABAergic mechanism, as well as NO pathway involvement in anticonvulsant activity of ZMEO were assessed by pretreating animals with Flumazenil, L-NAME, Aminoguanidine and L-Arginine in PTZ induced model of seizure. Administration of 20 mg/kg ZMEO could significantly increase chronic seizure threshold and latency while reducing frequency of convulsions and mortality in the PTZ-induced model. In studied doses, ZMEO could not protect mice from HLTE and mortality induced by MES. Pretreatment with L-arginine and diazepam potentiated anticonvulsant effects of ZMEO while pretreatment with L-NAME, Aminoguanidine and flumazenil reversed anticonvulsant activity. In conclusion, recorded anticonvulsant activity of ZMEO may be mediated in part through GABAergic mechanism and NO signaling pathway.