EVALUATION OF ANTICONVULSANT ACTIVITY OF ETHANOL LEAF EXTRACT OF Pavetta crassipes K. SCHUM (RUBIACEAE) ON 4-AMINOPYRIDINE AND PENTYLENETETRAZOLE INDUCED SEIZURES IN ALBINO MICE

Abstract

ABSTRACT

Epilepsy is one of the most common neurological disorders that is affecting more than 50 million people worldwide and it has several underlying causative factors. The chronic nature of epilepsy and the inability of the current drugs to have a long term seizure control in all patients has led to the need to investigate plants that are used in traditional medicine for the management of epilepsy. Pavetta crassipes (K. Schum) Rubiaceae is used in Northern Nigerian folk medicine to manage a range of diseases including epilepsy, cough and other diseases and its efficacy is well known in northern Nigeria. This study was carried out to determine the anticonvulsant effects of ethanol leaf extract of P. crassipes on mice using 4-aminopyridine and pentylenetetrazole (PTZ) induced seizure models at doses 250, 500 and 1000 mg/kg intraperitoneally. The intraperitoneal LD₅₀ in mice was estimated at 3807.88 mg/kg. The extract decreased the time for the onset of myoclonic jerk, the time for the onset of convulsion, the number of convulsion and the duration of convulsion at 250, 500 and 1000 mg/kg and also protected 80, 100 and 100% of the mice at 250, 500 and 1000 mg/kg doses respectively in the 4-aminopyridine-induced convulsion. The extract reduced the increased the latency of convulsion at 250, 500 and 1000 mg/kg. The extract reduced the number and duration of convulsion at 250. 500 and 1000 mg/kg and the extract protected 40%, 40% and 60% of the mice at 250, 500 and 1000 mg/kg against PTZ-induced seizures. The findings from the research suggest that ethanol leaf extract of P. crassipes has a potent anticonvulsant properties that are effective in the management of epilepsy and the maximum ameliorating effects observed in the 4-aminopyridine induced seizures suggests seizure control by the extract via interactions with potassium channels leading to decreasing neuronal, calcium channel blockade, leading to inhibition of the excessive influx of presynaptic Ca²⁺ caused by 4-AP and stabilization of neurons against the excessive glutamate concentrations generated by 4-AP. PTZ induced seizure showed ameliorating effects of the extract via enhancement of GABAergic neurotransmission in the brain by restoration of central GABAergic tone. The extract is also believed to counteract the mechanical channel antagonism imposed by PTZ, promoting a higher binding affinity for endogenous GABA molecules in the brain. This structural adjustment maximizes both the open-state frequency and duration of the integral Cl^- pore, reinstating inhibitory postsynaptic potentials (IPSPs) that blocks the propagation of seizure firing in the brain.