Neuropharmacological evaluation of the methanol leaf extract of Phyllanthus muellerianus (Kuntze) Exell and its ethyl acetate fraction in mice

Abstract

Purpose: To investigate the neuropharmacological effects of the methanol leaf extract (ME) and fractions of Phyllanthus muellerianus (PM) (Phyllanthaceae) (Kuntze) Exell (PM) in mice. Methods: Acute toxicity was carried out on the extract using standard protocol. ME was fractionated into hexane (HF), ethyl acetate (EF), and methanol (MF) fractions. Pentylenetetrazol (PTZ)-induced seizure, open field (OF) and motor coordination (rotarod) tests were models employed. Mice allotted into fourteen groups of six animals each were treated orally with 100, 200, or 400 mg/kg of the extract and fractions in pentylene tetrazole (PTZ) seizure model. Seizure was induced with intraperitoneal (ip) injection of 70 mg/kg of PTZ. The positive and negative controls employed were phenobarbitone (35 mg/kg) and 5 ml/kg of 7 % Tween 80, respectively. In the OF and motor coordination tests, six groups of six mice were treated orally with ME and EF at 200 and 400 mg/kg doses. Control groups received either 5 ml/kg of 7% Tween 80 or diazepam (1 mg/kg ip) as negative and positive controls respectively Results: In the PTZ model, only EF abolished seizures completely (p<0.05), when compared with the negative control, producing 100% protection, even better than the phenobarbitone which gave 83.3% protection. In the OFT, in comparison with the control, ME at 400 mg/kg (p < 0.05) decreased both the number of line crossing and the number of assisted rearing similar to that produced by diazepam. EF increased both the locomotor and exploratory activities significantly (p < 0.05) in mice. ME at 400 mg/kg significantly (p < 0.05) evoked reduction in the time of fall of mice from the rotarod when compared to the control in the same way as diazepam while EF did not elicit any appreciable differences. Conclusion: ME has anticonvulsant, sedative, and anxiolytic activities, while EF possesses anticonvulsant and anxiolytic activities devoid of sedative and cognitive impairment. The observed anticonvulsant effect was better than that produced by phenobarbitone. Thus, it may be a good lead for developing antiepileptic and other central nervous system active agents.