METHANOL EXTRACT OF Ficus platyphylla AMELIORATES THE SEVERITY OF LITHIUM-PILOCARPINE-INDUCED STATUS EPILEPTICUS IN RATS

Pilocarpine model of epilepsy reproduces features of temporal lobe epilepsy (TLE) associated with mossy fiber sprouting, gliosis, and extensive loss of dentate gyrus and hippocampal pyramidal neurons. TLE is often resistant to drug treatment, proceeding from impaired mitochondrial energy production and failure of GABAergic inhibition. In this study, Ficus platyphylla (FP) was extracted with methanol and the methanol extract subjected to Gas Chromatographic-Mass Spectrometric (GC-MS) and Fourier-transform infrared spectroscopic (FT-IR) analyses. In silico molecular docking study was conducted to predict interactions of the major compounds from FP with glutamic acid decarboxylase (GAD) and γ-aminobutyric acid aminotransferase (GABAAT). Effects of FP on lithium-pilocarpine-induced status epilepticus (SE) and neuronal cell damage were examined, and the involvement of oxidative and GABAergic pathways investigated to define the likely target(s) for development of the bioactive components. FP at doses of 50, 100 and 200 mg/kg, protected 8%, 27% and 20% of rats from lithium-pilocarpine-induced status epilepticus (SE), respectively. FP alleviated lithium-pilocarpine-induced seizure severity (p < 0.01) and extended the latencies to seizures (p < 0.001) and SE (p < 0.001) in non-protected rats. The extract ameliorated neuronal cell damage and oxidative stress induced by lithium-pilocarpine administration. FP significantly (p < 0.001) increased the expression of genes encoding glutathione-S-synthase (GSS), superoxide dismutase (SOD), catalase (CAT), and glutamic acid decarboxylase (GAD). The major compounds in the extract including octadecenoic acid, dimethylphenylisothiocyanate, and pentadecanoic acid showed interaction with GAD and GABAAT active sites. These preliminary findings revealed the ameliorative effects of FP against lithium-pilocarpine-induced status epilepticus, neuronal cell damage and alterations of oxidative stress biomarkers. Bioactive compounds in the extract interacted with GAD and GABAAT active sites. Further studies are required to unravel the potential values of bioactive constituents of FP for the management of temporal lobe epilepsy.