Anticonvulsant activity of an active fraction extracted from Crinum jagus L. (Amaryllidaceae), and its possible effects on fully kindled seizures, depression-like behaviour and oxidative stress in experimental rodent models

Abstract

Ethnopharmacological relevanceThe leaf extract of Crinum jagus L. (Amaryllidaceae) is widely used in traditional Cameroonian medicine as antiepileptic remedy and for the treatment of convulsion, depression and mood disorders associated with epilepsy. Aim of the studyHence, this study was conducted to evaluate the effects of an active fraction extracted from the leaves of Crinum jagus against seizures, depression-like behaviour and oxidative stress in pentylenetetrazole (PTZ)-induced kindling in mice. Materials and methodsBioactive-guided fractionation of the leaf extract of Crinum jagus by using 70mg/kg PTZ-induced convulsions in mice, afforded a potent anticonvulsant fraction (flavonol kaempferol; C4.4). The effects of C4.4 on 30mg/kg PTZ-induced kindling, kindling-induced depression like-behaviour and oxidative stress was evaluated. Mice were injected PTZ (30mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Depression was assessed using tail suspension test and forced swim test while the oxidative stress parameters were estimated in the whole brain at the end of experiments. Mice were submitted to the rota-rod task and open-field test in order to assess any non-specific muscle-relaxant or sedative effects of C4.4. Acute toxicity of C4.4 was also assessed in mice. ResultsConvulsions-induced by 70mg/kg PTZ were strongly antagonized by C4.4. Oral administration of C4.4 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 PTZ-kindled mice. The data indicated also that C4.4 significantly reduced the immobility times in the tail suspension test and the forced swim test. This active fraction has also antioxidant properties by decreasing the lipid peroxidation, and augmenting endogenous antioxidant enzymes in brain. C4.4 administered (12.5–50mg/kg) did not alter the locomotion of animals in the open-field or rotarod tests, which suggest a lack of a central depressant effect. The animals did not exhibit any acute toxicity to C4.4 at the therapeutic doses. ConclusionThese results suggest that pretreatment with C4.4 ameliorates convulsions-induced by PTZ, protects mice against kindling development, depression-like behaviour and oxidative stress in PTZ-kindled mice. These finding provides scientific rationale for the use of Crinum jagus extracts for the amelioration of epilepsy observed in traditional medicine in Cameroon.