Abstract

CAMPYLONEURUM PHYLLITIDIS AQUEOUS EXTRACT EXHIBIT ANTIEPILEPTOGENIC AND NEUROPROTECTIVE EFFECTS IN MICE MODEL OF MESIALTEMPORAL LOBE EPILEPSY: POTENTIATION OF GABAERGIC AND ANTIOXIDANT PATHWAYS

Nkegne Steve Melton, Kandeda Kavaye Antoine, Minoue Kuum Marc Germain*, Mabou Talom Symphorien and Ndeva Baldagai

ABSTRACT

Mesio-temporal lobe epilepsy accounts for over 80% of all temporal lobe seizures and is treatment-resistant. Campyloneurum phyllitidis (Polypodiaceae) is an epiphytic fern used in traditional medicine in Africa. Using in vivo experimental paradigms, we investigated the anti-epileptogenic and neuroprotective properties of C. phyllitidis leaf aqueous extract. Status epilepticus generated by pilocarpine injection (325 mg/kg) lasted 30 minutes and resulted in epileptogenesis in the rats. The occurrence of spontaneous recurring seizures in the negative control group on day 11 completed this epileptogenesis phase. During this time, the status epilepticus rats were divided and treated orally as follows: a negative control group received distilled water (10 mL/kg), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of C. phyllitidis (90, 180, and 360 mg/kg, p.o.). During the treatment period, the animals were videotaped for two weeks to assess the average latency time of the first spontaneous tonic-clonic seizure, the average number and duration of spontaneous seizures, and the latter were subjected to anxiety and memory tests. Finally, the animals were sacrificed for biochemical and hippocampal-histological analyses of the hippocampus. Antioxidant activities and involvement of GABAergic neurotransmission were determined by measuring levels of GABA, GABA-transaminase (GABA-T), malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD). The results demonstrate that C. phyllitidis aqueous extract considerably enhanced the mean latency time of the onset of the first spontaneous tonic-clonic seizure and significantly decreased the mean frequency and duration of spontaneous seizures compared to the negative control. For anxiety disorders, the extract greatly increased time spent in the open quadrant, in the middle of the device, and significantly decreased the number of rearing and grooming. Regarding memory impairments, the extract considerably enhanced the time spent exploring the new object in the preferred arm and significantly decreased the time spent investigating the old item in the discriminating arm. Biomarker assays demonstrated a large rise in the concentrations of GABA and GSH, as well as a significant decrease in the concentrations of MDA, SOD activity, and GABA-T. Histological examination demonstrated that the extract slowed the degradation of neurons in the CA1, CA3, and dentate gyrus areas. These findings imply that the aqueous extract of C. phillitidis has antiepileptogenic and neuroprotective properties that are mediated in part by GABAergic and antioxidant activities.

Keywords: Epileptogenesis, Campyloneurum phyllitidis, GABA, Oxidative stress, Neuroprotection.