BackgroundThe alarming expansion of drug resistance, as well as the scarcity of effective antimalarial medications currently accessible, highlights the importance of finding novel antimalarial chemicals. This study was undertaken to evaluate the antiplasmodial efficacy, antioxidant, and cytotoxicity of Terminalia macroptera stem bark in order to justify it as an antimalarial agent for the local population. MethodologyAqueous and ethanol extracts of the stem bark were prepared using standard procedures. The antimalarial activity of the plant extract was investigated in culture using the fluorescence-based SYBR Green assay against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains. The antioxidant activity was determined by measuring ferric reducing antioxidant power, 1,1-diphenyl-2-picrylhydrazyl, free radical scavenging, and nitric oxide radical scavenging. Cytotoxicity of the extracts was conducted against RAW 264.7 cell line and red blood cells. ResultsThe aqueous and ethanolic extracts of T macroptera were active with inhibitory concentration 50 (IC50) for 3D7 strains of 3.46 ± 0.48 and 4.10 ± 0.39μg/ml for the aqueous and ethanolic extracts, respectively. The same activity was obtained with the Dd2 strain with IC50 of 6.15 ± 1.46 and 7.47 ± 0.03μg/ml for the aqueous and ethanolic extracts, respectively. The aqueous extracts showed good free radical scavenging property. The IC50 of the aqueous extract was found to be 0.87, 8.49, 72.78, and 25.92μg/ml for 1,1-diphenyl-2-picrylhydrazyl, nitric oxide, H2O2, and ferric reducing antioxidant power, respectively. For the cytotoxicity test, aqueous and ethanolic extracts of T macroptera were non-toxic with a CC50 value of 292.55 ± 1.35 and 223.25 ± 2.75 µg/ml for ethanolic and aqueous, respectively. Regarding the cytotoxicity of the extracts on red blood cells (haemolysis), the two extracts showed very low toxicity compared to the positive control. Phytochemical screening of the plants extract revealed the presence of alkaloids, triterpenoids, anthocyanins, anthraquinons, saponins, flavonoids, and phenolics. ConclusionsThese findings suggest that extracts of T macroptera can serve as antimalarial agents. Further in vivo, antimalarial, antioxidant, and toxicity studies are required to scientifically validate the use of T macroptera as an antimalarial agent.