Anticonvulsant effects of iridoid glycosides fraction purified from Feretia apodanthera Del. (Rubiaceae) in experimental mice models of generalized tonic-clonic seizures

BACKGROUND: Despite the increasing number and variety of antiepileptic drugs, nearly 30 % of epileptic patients who receive appropriate medical attention have persisting seizures. Anticonvulsant activity has been demonstrated for different iridoid glycoside-rich plant extracts. This study was designed to investigate the anticonvulsant effects of iridoid glycosides purified from Feretia apodanthera and to explore the possible mechanisms involved in antiepileptic activity. METHODS: The anticonvulsant effects of iridoid glycosides extracts were investigated against 2.7 mg/kg bicuculline- and 70 mg/kg pentylenetetrazole-induced convulsions. The behavioural and electroencephalographic manifestations of 50 mg/kg pentylenetetrazole-induced seizures in mice as a model of generalized tonic-clonic seizures were also evaluated. Finally, the extracts were tested on the course of kindling development, kindled-seizures and oxidative stress markers in 30 mg/kg pentylenetetrazole-kindled mice. Their effects on brain GABA content were also determined. RESULTS: The iridoid glycosides (30–90 mg/kg) protected mice against bicuculline-induced motor seizures in all pre-treated animals. Behavioural seizures- and mortality-induced by 70 mg/kg pentylenetetrazole were strongly antagonized by the extracts (60–90 mg/kg). The number of crisis (n/20 min), the cumulative duration of crisis (sec/20 min), and the mean duration of crisis (sec) recorded in 50 mg/kg pentylenetetrazole-treated mice were significantly decreased in all pre-treated mice with the extracts (60–90 mg/kg). Administration of the extracts (30–90 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure mean stage and decreased the number of myoclonic jerks in 30 mg/kg pentylenetetrazole-kindled mice. Pentylenetetrazole kindling induced significant oxidative stress and brain GABA content alteration that was reversed by pretreatment with the extracts in a dose-dependent manner. CONCLUSIONS: The results indicate that pretreatment with the iridoid glycosides extracts of Feretia apodenthera improves generalized tonic-clonic seizures-induced by chemo-convulsants, protects mice against kindling development and oxidative stress, and improves brain GABA content in pentylenetetrazole-kindled mice.