In vitro antiplasmodial activities of extract and fractions from Lepidobotrys staudtii against sensitive and resistant blood-stage parasites of Plasmodium falciparum

Antimalarial resistance is a primary challenge in the treatment of malaria. The ongoing search for novel drug sources remains a critical strategy for addressing this issue. This study evaluated the blood stage antiplasmodial and cytotoxic activities of the crude extract and fractions obtained from Lepidobotrys staudtii. The crude extract and all fractions exhibited promising antiplasmodial activity (IC₅₀ < 10 μg/mL) against all the tested Plasmodium falciparum strains (Pf3D7 drug-sensitive and PfINDO chloroquine-resistant). Notably, the hexane and ethyl acetate fractions exhibited the highest potency, with IC₅₀ values of 3.73 and 3.4 μg/mL (Pf3D7), respectively. No cytotoxic effects were observed at concentrations of up to 500 μg/mL. The ethyl acetate fraction displayed rapid action (12 h of exposure) against the Pf3D7 and PfINDO strains. The ring stage parasites were particularly susceptible to the fractions, with IC₅₀ values ranging from 2.17 to 4.87 μg/mL (Pf3D7) and 2.27-6.27 μg/mL (PfINDO). Additionally, combining the fraction with standard antimalarials at fixed sub-inhibitory concentrations significantly reduced IC₅₀ values. Only the hexane and crude extracts stimulated reactive oxygen species (ROS) production, whereas the other fractions neutralized the ROS. The most potent ethyl acetate fraction arrested parasite developmental progression and merozoite egress. Phytochemical analyses revealed the presence of phenols, flavonoids, tannins, alkaloids, saponins, carbohydrates, glycosides, and proteins. Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis revealed that the fractions comprised a diverse array of compounds, resulting in varying levels of parasite-killing. This study emphasizes the blood-stage antiplasmodial properties of the stem bark extract and fractions of L. staudtii, underscoring their potential as a promising source of antimalarial agents.