Neuroprotective Effect of Dacryodes edulis Ethanolic Leaf Extract on the Prefrontal Cortex and Long-term Learning and Memory in Wistar Rats of Ketamine-Induced Neurotoxicity

Introduction: Dacryodes edulis (African pear) is a medicinal plant known for its medicinal qualities. Its extracts are said to possess many health-promoting constituents such as antioxidants that have been used to treat many illnesses, including neurological disorders. Drug-induced neurological disorders usually affect the normal functioning of brain parts, including the prefrontal cortex and hippocampus.

Aims: The aim of this study was to investigate the effect of Dacryodes edulis ethanolic leaf extract on the cytoarchitecture of the prefrontal cortex. Another objective was to determine spatial learning and memory in the rats.

Methods: Forty-six (46) rats were used for this study. Sixteen (16) rats were used for acute toxicity test of the leaf extract, while 30 were divided into five groups of six rats each. The control group was designated as group A and given food and water only, while the Ketamine control group (group B) was administered with 100mg/kg body weight “BW” of Ketamine. Groups C, D and E were given Ketamine (100mg/kg BW) + Diazepam (0.3mg/kg BW), Ketamine (100mg/kg BW) + 1000mg/kg BW Dacryodes edulis ethanolic leaf extract and Ketamine (100mg/kg BW) + 500mg/kg BW Dacryodes edulis ethanolic leaf extract respectively for 28 days. The ketamine and diazepam were administered intraperitoneally, while the leaf extract was administered with the aid of an oro-gastric tube. The histology of the prefrontal cortex, as well as spatial learning and memory were determined afterwards.

Results: The histological result revealed marked atrophic cellular changes in the prefrontal cortex of groups B rats (treated with Ketamine alone) and C (treated with Ketamine and Diazepam) as revealed by the cytometric study. Group D rats treated with 1000mg/kg BW of Dacryodes edulis extract displayed average neuronal cell size relatively similar to that of group A rats, while group E rats treated with 500mg/kg BW of Dacryodes edulis extract showed marked atrophic cellular changes. The neurobehavioral study with the use of Morris water maze revealed significant decrease in escape latency in group D during the acquisition and reversal training period when compared to groups B, C and E. During the probe trial day, group A exhibited the longest duration spent in the retention quadrant, while group D rats (1000mg/kg BW of Dacryodes edulis extract) spent a longer time in the quadrant when compared to groups B, C and E. This is indicative of improved spatial learning and memory capability in the group D rats. The result therefore indicates ameliorative potential of the leaf extract but only in the high dose group.

Conclusion: The leaf extract of Dacryodes edulis can be considered as an alternative neuroprotective drug in cases of Ketamine-induced neurodegeneration.