Toxicity Studies and in vivo Antiplasmodial Evaluation of Leaf and Stem Bark Extracts of Terminalia avicennioides

Abstract

Malaria is one of the most serious infectious diseases found in the tropics and subtropics. P. falcifarum resistance to almost all anti-malarial drugs has necessitated the search for anti-malarial compounds. The aim of this study is to investigate the antiplasmodial effects of crude leaf and stem bark extracts of T. avicennioides, a plant utilized by traditional healers in Northern Nigeria to treat malaria and other ailments. Brine shrimp lethality (cytotoxicity) assay and acute toxicity were also evaluated, which are considered a useful tool for preliminary assessment of toxicity in plant extracts. The median lethal dosage (LD50) was calculated by administering different doses of the extract (100–4000 mg/kg) intraperitoneally to three groups of three mice each for 24 hours and observing the animals for physical sign of toxicity. Three models were employed to assess the extracts antiplasmodial effectiveness in vivo against the rodent malaria parasite Plasmodium berghei: suppressive, curative, and repository. The leaf and stem bark extracts were found to show significant toxicity to brine shrimp larvae of Artemia salina in the brine shrimp lethality test with LC50 values of >1000 and 29.6 respectively. Excitation, paw licking, and death were symptoms of acute toxicity of the extracts based on physical and behavioral observations. Death was recorded at 1000 mg/Kg of the stem bark extract and the LD50 is ≤100 mg/Kg body weight while for the leaf extract it was estimated to be ≤600 mg/Kg with no death record. In vivo evaluation revealed that the extracts significantly (P <0.05) reduced parasite count in all models (suppressive, curative and prophylactic), with high average percentage inhibition of parasitaemia (54.68, 58.67 and 65.61%) seen in both T. avicennioides leaf and stem bark extracts, which was comparable to that produced by chloroquine and artesunate, respectively (64.31&93.1; 70.08&80.67; 63.40&75.20%). Both extracts had moderate antiplasmodial activity and were non-toxic to mice and brine shrimps. This finding validates the plant's traditional use in malaria treatment.