Neurohistological and immunohistochemical effects of prophylactic ethanolic leaf extract of Nauclea latifolia and Artemether/Lumefantrine on the hippocampus of Plasmodium berghei-infected mice

Abstract

The prophylactic effect of ethanolic leaf extract of Nauclea latifolia, widely used in herbal malarial treatment, was compared against standard drug Coartem® (Artemether/Lumefantrine) in Plasmodiuminfected mice was investigated, and thereafter analysed for organosomatic index, parasitemia, histomorphological and immunohistochemical changes in the hippocampus. Twenty male mice about 6 to 8 weeks weighing 20 to 24 g were alloted into four groups of five mice each. Group 1 served as control received placebo; group 2 received extract 500 mg/kg; group 3 received extract 1000 mg/kg; and group 4 received 5 mg/kg of Artemether/Lumefantrine. Extract and drug administrations were performed for 3 days, and thereafter mice were infected with 10 6 of Plasmodium berghei parasites, and monitored for 4 days, after which the experiment was terminated. Thick blood smear were prepared from lateral tail vein, then under anesthesia via a cocktail of xylaxine and ketamine, intracardiac perfusion was performed first with phosphate buffered saline to clear systemic blood, and then 4% paraformaldehyde to fixed brain for routine histology and immunohistochemistry. Result indicates organosomatic index was not statistically significant, parasitemia in the treated groups were significantly (p<0.05) decreased compared to control and were corroborated in the photomicrographs of respective blood morphology, however, histologically there was moderate to severe distortion of the hippocampus across the groups, but glial fibrillary acidic protein expression, a marker for neurotoxicity indicated that group 4 had the most immunolabelling intensity compared to other test groups. In conclusion, the prophylactic ethanolic extract of N. latifolia and Artemether/Lumefantrine cleared parasitemia also seen in the blood morphology, and low dose N. latifolia plausibly has better safety and hippocampal toxicity profile with decreased neuronal shrinkage and distortions, with a more down regulated glial fibrillary acid protein than higher extract doses and Artemether/lumefantrine.