In- vitro assessment of the anti- malarial potential of Alpha Onocerin; cytotoxicity and hemolytic effect, multi-stage activity and molecular docking

The surfacing of resistant strains of Plasmodium falciparum (P. falciparum) against various antimalarials on the market has intensified the need for novel antimalarial agents, particularly those with multistage efficacy. This study investigated the safety and anti-plasmodial efficacy of alpha onocerin (AOC), a triterpenoid compound derived from Huperzia phlegmaria, against both 3D7 and Dd2 lab strains of P. falciparum. In vitro anti-plasmodial assays were carried out to investigate the activity of AOC across trophozoite, schizont, and gametocyte stages. The SYBR Green assay was used to quantify parasite growth after 72 h of incubation. The cytotoxic effect of AOC was tested against the HepG2 cell using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. AOC exhibited significant stage-specific anti-plasmodial activity, with IC₅₀ values of 2.30 ± 0.44 µM (trophozoites) and 3.96 ± 0.72 µM (schizonts) for 3D7, with Dd2 yielding 6.33 ± 0.63 µM (trophozoites) and 13.76 ± 1.09 (schizonts). Molecular docking further revealed potential interactions of AOC with parasite targets, suggesting a probable mechanism involving disruption of parasite metabolism or membrane integrity. These findings underscore the promise of the compound as a viable lead candidate for antimalarial drug development, supported by its broad inhibitory activity against P. falciparum.