IntroductionResistant malaria is a fatal disease. Globimetula braunii (African Mistletoe) is traditionally used for malarial treatment but this fact has not been scientifically reported.MethodsPlasmodium berghei (NK65)-infected male Swiss mice (20±2 g) were treated orally and once daily with 100, 200, and 400 mg/kg BW of methanol extract and its respective hexane, dichloromethane and ethyl acetate fractions for 9 days. P-alaxin was used as control drug P. berghei (ANKA)-infected mice were then treated with the most potent fraction for 5 days. Parasitemia and parasite clearance were determined by microscopy, while hematological parameters, heme, hemozoin, and mouse erythrocyte membrane stabilisation were assayed. The phytochemicals in the most potent fraction were identified using gas chromatography-mass spectrometry.ResultsHexane fraction (HF)-treated mice (400 mg/kg BW) had the least mean parasite load (0.00 ± 0.00; 0.14 ± 0.05%) and highest clearance (100 ± 0.00; 75.50 ± 4.95%) compared with infected control (9.81 ± 0.09; 6.84 ± 0.09%) in susceptible and resistant models, respectively. Hexane fraction modulated hematological indices, minimised erythrocyte membrane damage in heat-induced (2.18 ± 0.94%) and hypotonic solution-induced (7.93 ± 0.93%) compared to artequin (5.05 ± 2.18; 6.38 ± 0.33%) and P-alaxin (67.45 ± 5.15; 56.78 ± 1.10%) in both models of membrane stabilisation, respectively. Hexane fraction (P<0.01) increased heme and decreased hemozoin contents. Friedelan-3-one was identified as the most abundant triterpene.ConclusionThe results indicated that G. braunii has anti-plasmodial properties and minimally dis-stabilised erythrocyte membrane. The major findings in this study are that n-hexane fraction of G. braunii possess excellent and moderate antiplasmodial activity against susceptible and resistant P. berghei, respectively. This was reflected via decreased parasite load, improved hematological parameters, increased heme and decreased hemozoin contents. Friedelan-3-one, a major constituent of the n-hexane fraction, may be responsible for this activity.