Anti-plasmodial effects of Azadirachta indica in experimental cerebral malaria: Apoptosis of cerebellar Purkinje cells of mice as a marker.

Background: Malaria is a major public health problem in the world, but treatment of malaria is becoming more difficult due to increasing drug resistance. Therefore, the need for alternative drugs is acute.

Aims: This study investigated the antiplasmodial and protective effect of an ethanolic extract of the leaves from a traditionally used medicinal plant, Azadirachta indica (Neem) in a mouse model of malaria.

Materials And Methods: Swiss albino mice were intraperitoneally infected with 10×10(6)Plasmodium berghei ANKA, a rodent malaria parasite. The presence of parasites was checked by microscopic examination of blood samples daily. Ethanolic extracts of Neem at 300, 500 and 1000 mg/kg were administered intraperitoneally daily for five days from the day parasitaemia reach 5% of parasite inoculation. Intraperitoneal chloroquine and artemether were used as standard drug treatment controls. Symptoms of neurological or respiratory disorder, mortality, weight and temperature were recorded. Histological sections of brain were prepared and examined after staining with hematoxylin-eosin and immunohistochemistry for apoptotic cells.

Results: All Neem treatment groups displayed parasitaemia that gradually increased during treatment, and showed signs of terminal illness (i.e. hypothermia, ptosis and convulsions) within 2-4 days post-treatment. In contrast, the chloroquine and artemether groups showed no cerebral malaria symptoms and no deaths. Apoptosis in Purkinje cells, cerebral haemorrhage and oedema were found in some of the mice treated with Neem and chloroquine.

Conclusions: Azadirachta indica (Neem) extract was not protective against malaria symptoms and signs in this mouse model. However, a difference in the number of apoptotic Purkinje cells between the untreated control group and Neem treatment at 500 mg/kg suggests that Neem may have some neuronal protective effect.