AntiConvulsant And Sedative Effects Of The Hydro-Ethanolic Whole Plant Extraction Of Cleome Ruicetidosperma (DC.) (CLEOMECEAE) In Mice.

ABSTRACT

BACKGROUND:

Cleome rutidosperma (DC.) (Family: Cleomeceae) is a low-growing herb used for the treatment of epilepsy in African traditional medicine. This study presents the anticonvulsant, sedative effects and safety profile of the hydro-ethanolic extract of the whole plant of Cleome rutidosperma (CRE) in murine experimental models. METHODS: Preliminary phytochemical screening of the extract was conducted using standard colorimetric assays. The general effect of the extract, CRE (10, 30, 100, 300, 1000 and 3000 mg kg-1 p.o.) on the central nervous system of mice was assessed using the Irwin test. The anticonvulsant screening of CRE (100, 300 and 1000 mg kg-1 p.o.) utilized four murine models of experimental epilepsy; pentylenetetrazole (PTZ)-, picrotoxin (PIC)-, maximal electroshock (MES)- induced seizures and pentylenetetrazole-induced kindling. Phenobarbitone and carbamazepine were used as reference anticonvulsant agents in the anticonvulsant screening experiments. The duration, frequency and latency to seizures were measured for each treated animal. The extract’s ability to induce sedation was also investigated using the thiopental sleeping time test. Acute and subacute toxicity studies were conducted to determine the safety of the extract in mice. RESULTS: Preliminary phytochemical screening indicated the presence of flavonoids, alkaloids, glycosides, phytosterols and saponins. In the Irwin test, the extract produced sedation as its major effect. In the acute seizure models, the extract caused significant increase in the latency to seizure (P< 0.0001) and a significant reduction in the duration of tonic-clonic convulsions (P< 0.0001) in PTZ- induced seizure model. Also, the extract significantly decreased duration of seizures (P< 0.0001) and increased the latency to seizure in the PIC- induced seizure model (P< 0.0001). In the MES test, the extract did not significantly reduce the duration of hind limb tonic extension (P= 0.6446) and it did not increase the latency to hind limb tonic extension (P= 0.3257). In PTZinduced kindling test, the extract significantly (P=0.0002) reduced the percentage severity of seizures in the mice and prevented the animals from being fully kindled. The extract (30, 100, 300 and 1000 mg kg-1 p.o.) dose-dependently and significantly decreased the latency to sleep (P< 0.0001) and increased significantly the duration of sleep (P< 0.0001) induced by thiopental sodium. There were no deaths recorded in the acute toxicity studies even at a dose of 3000 mg kg1 thus the LD50 was estimated to be more than 3000 mg kg-1. The relative organ to body weight ratio for both control and treatment groups were not significantly different in both acute (P= 0.9987) and subacute (P= 0.9887) toxicity studies. Histopathological examination of the brain, and heart showed no prominent abnormalities in the extract-treated group. However, the histopathological examination of the kidney and liver showed tubular dilatation with erythrocyte infiltration and hepatocellular oedema respectively. CONCLUSIONS: The hydro-ethanolic extract of the whole plant of Cleome rutidosperma produces anticonvulsant and sedative effects in mice. The extract was relatively safe in the acute and sub-acute toxicity investigations in mice, with an LD50 greater than 3000 mg kg-1 .