Evaluation of anti-epileptic activity of leaf extracts of Punica granatum on experimental models of epilepsy in mice

OBJECTIVES: This study was aimed to examine the anti-epileptic activity of leaf extracts of Punica granatum in experimental models of epilepsy in Swiss albino mice. MATERIALS AND METHODS: Petroleum ether leaf extract of P. granatum (PLPG), methanolic LPG (MLPG), and aqueous LPG (ALPG) extracts of P. granatum leaves was initially evaluated against 6-Hz-induced seizure model; the potent extract was further evaluated against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Further, the potent extract was evaluated for its influence on Gamma amino butyric acid (GABA) levels in brain, to explore the possible mechanism of action. In addition, the potent extract was subjected to actophotometer test to assess its possible locomotor activity deficit inducing action. RESULTS: In 6-Hz seizure test, the MLPG has alleviated 6-Hz-induced seizures significantly and dose dependently at doses 50, 100, 200, and 400 mg/kg. In contrast, PLPG and ALPG did not show any protection, only high dose of ALPG (400 and 800 mg/kg, p.o.) showed very slight inhibition. Based on these observations, only MLPG was tested in MES and PTZ models. Interestingly, the MLPG (50, 100, 200 and 400 mg/kg) has offered significant and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. Further, MLPG showed a significant increase in brain GABA levels (P < 0.01) compared to control and showed insignificant change in locomotor activity in all tested doses (100, 200 and 400 mg/kg). Interestingly, higher dose of MLPG (400 mg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) have completely abolished the convulsions in all the anticonvulsant tests. CONCLUSION: These findings suggest that MLPG possesses significant anticonvulsant property, and one of the possible mechanisms behind the anticonvulsant activity of MLPG may be through enhanced GABA levels in the brain.