The effect of Artemisinin on the Pentylentetrazole-induced seizures during the estrous cycle and GABA interaction in mice

Catamenial epilepsy may involve ۱۰ to ۷۰% of women with epilepsy in which, seizures are exacerbated by the menstrual cycle. Artemisinin is a herbal compound with widespread modern and traditional medical indications. Because of GABAergic interaction, this study was designed to study the antiepileptic effects of Artemisinin during the estrus cycle.  A total of ۳۶۰ adult female mice were placed in ۱۰ groups: control, solvent (ethanol ۱۰ml/kg), Artemisinin (۷۵&۱۵۰ mg/kg), Bicuculline (۲mg/kg), Bicuculline (۲mg/kg) + Atremisinin (۷۵&۱۵۰ mg/kg), Saclofen (۲mg/kg), Saclofen (۲mg/kg) + Atremisinin (۷۵&۱۵۰ mg/kg), each with four subgroups (proestrus, estrus, metestrus and diestrus) (n=۹). One week after acclimatization, estrous synchronization and phase determination was achieved. Acute epilepsy was induced by intraperitoneal (i.p) injection of ۸۰ mg/kg of Pentylentetrazole (PTZ), ۳۰ minutes after i.p injection of Artemisinin and ethanol. Initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were recorded for ۳۰ minutes. Data were displayed as mean ± SD and evaluated using one-way ANOVA followed by Tukey–Kramer multiple comparison post hoc tests (p < ۰.۰۵). Artemisinin significantly decreased epilepsy incidence, duration, and mortality rate, in parallel to increasing ITMS and ITTS in a dose-dependent manner which were more prominent during the luteal phase. Co-administration of Biccucluline significantly inhibited antiepileptic effects of Artemisinin, while Saclofen did not have such an inhibitory interaction. It seems that increased neurosteroid metabolites and GABAA receptors, neural hyperpolarization following GABA interaction, and anti-inflammatory and anti-oxidative properties which decrease neuroinflammation and neural excitability can participate in the antiepileptic effects of Artemisinin.

Keywords:

Artemisinin , Catamenial epilepsy , Estrous cycle , GABA