ANTIDIABETIC ACTIVITY AND TOXICOLOGICAL EVALUATION OF THE METHANOL-DICHLOROMETHANE ROOT BARK EXTRACT OF NAUCLEA DIDERRICHII (DE WILD) MERR

Objective: In southeastern Nigeria, Nauclea diderrichii (De Wild) Merr is used in the treatment of a wide range of ailments including diabetes mellitus (DM). This study evaluates the antidiabetic activity and toxicological profile of the methanol-dichloromethane root bark extract of N. diderrichii in normoglycemic and alloxan-induced diabetic models.Methods: Dried root barks of N. diderrichii were extracted using methanol and dichloromethane (1:1) to obtain N. diderrichii extract (NDE). The acute and sub-chronic toxicity tests were performed using standard procedures. The effect on alanine aminotransferase (ALT) aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), packed cell volume (PCV), hemoglobin concentration (HB) and total white blood cell (TWBC) count was determined in the rats after treatment. In order to elucidate its antidiabetic mode of action, an oral glucose tolerance test (OGTT) was performed using glucose (2 g/kg) as substrate and alloxan (100 mg/kg; i. v.) induced diabetic model. Glibenclamide (GLI 0.2 mg/kg) was used as the reference standard drug.Results: The results indicated that the LD50 of the extract is>5000 mg/kg. ALT, AST, ALP PCV, HB and TWBC were insignificantly (p>0.05) different compared with the control. No significant changes were observed in the organ weights compared with the control. In the acute and prolonged antidiabetic study, NDE (100, 200 and 400 mg/kg) significantly reduced the blood glucose level (BGL) by 14.66, 18.9, 25.80% and 75.11, 80.24, 83.74% respectively. In comparison, GLI, when administered, reduced BGL by 38.18 and 92.86% respectively.Conclusion: N. diderrichii possesses antidiabetic activity with good toxicological profile

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

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