Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Clin Transl Sci. 2020 Jul;13(4):785-797. doi: 10.1111/cts.12767. Epub 2020 Apr 8.
The essential oil from the leaves of Zhumeria majdae Rech. (ZMEO) has been shown to have several beneficial effects in the clinic. In this work we examined the anticonvulsant activities of ZMEO in an experimental mouse model of seizure and aimed to identify any possible underlying mechanisms. ZMEO (5, 10, 20, and 40 mg/kg intraperitoneally (i.p.)) or diazepam, as the reference anticonvulsant drug (25, 50 and 100 µg/kg i.p.), were administered 60 minutes prior to pentylenetetrazol (PTZ) injection (intravenously (i.v.) or i.p.) and changes in threshold, latency, and frequency of clonic seizure were examined. The PTZ i.p.-induced model of seizure was also applied for examining the protective effects of ZMEO pretreatment against PTZ-induced mortality. In some studies, the anticonvulsant effect of the combination of diazepam and ZMEO was also studied. The protective effects of ZMEO against hindlimb tonic extensions (HLTEs) were also examined by maximal electroshock (MES) seizure testing. The γ-aminobutyric acid (GABA)ergic mechanism and nitric oxide (NO) pathway involvement in anticonvulsant activity of ZMEO were assessed by pretreating animals with flumazenil, N -nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and L-arginine in a PTZ-induced model of seizure. Administration of 20 mg/kg ZMEO significantly increased chronic seizure threshold and latency while reducing frequency of convulsions and mortality in the PTZ-induced model. In the doses studied, ZMEO could not protect mice from HLTE and mortality induced by MES. Pretreatment with L-arginine and diazepam potentiated the anticonvulsant effects of ZMEO, whereas pretreatment with L-NAME, aminoguanidine, and flumazenil reversed anticonvulsant activity. The anticonvulsant activity of ZMEO may be mediated in part through a GABAergic mechanism and the NO signaling pathway.
朱美叶的叶子精油（ZMEO）已被证明在临床上具有多种有益作用。在这项工作中，我们研究了 ZMEO 在实验性癫痫小鼠模型中的抗惊厥活性，并旨在确定任何可能的潜在机制。ZMEO（5、10、20 和 40mg/kg 腹腔内（i.p.））或地西泮，作为参考抗惊厥药物（25、50 和 100μg/kg i.p.），在戊四氮（PTZ）注射（静脉内（i.v.）或 i.p.）前 60 分钟给予，并检查了惊厥发作的阈值、潜伏期和阵挛发作频率的变化。还应用了 PTZ i.p.诱导的癫痫发作模型，以检查 ZMEO 预处理对 PTZ 诱导的死亡率的保护作用。在一些研究中，还研究了地西泮和 ZMEO 联合的抗惊厥作用。还通过最大电休克（MES）惊厥测试检查了 ZMEO 对后肢强直伸展（HLTE）的保护作用。通过用氟马西尼、N-硝基-L-精氨酸甲酯（L-NAME）、氨基胍和 L-精氨酸预处理动物，评估了 ZMEO 的抗惊厥活性中的γ-氨基丁酸（GABA）能机制和一氧化氮（NO）途径参与。在 PTZ 诱导的癫痫发作模型中，给予 20mg/kg ZMEO 可显著增加慢性惊厥阈值和潜伏期，同时降低 PTZ 诱导的模型中的惊厥发作频率和死亡率。在所研究的剂量下，ZMEO 不能保护小鼠免受 MES 诱导的 HLTE 和死亡率。L-精氨酸和地西泮预处理增强了 ZMEO 的抗惊厥作用，而 L-NAME、氨基胍和氟马西尼预处理则逆转了抗惊厥活性。ZMEO 的抗惊厥活性可能部分通过 GABA 能机制和 NO 信号通路介导。
