Synergistic action of phytoconstituents drives the anthelmintic potential of Croton penduliflorus stem bark extracts

The growing resistance to anthelmintic drugs highlights the urgent need for new, plant-derived therapeutics. This study investigates the synergistic anthelmintic activity of Croton penduliflorus stem bark extracts. Soxhlet extraction yielded 3.06% from the stem bark, with phytochemical screening revealing sterols as dominant constituents. The stem bark extract showed strong activity against Eudrilus eugeniae, causing paralysis and death within 8 ± 0.6 and 15 ± 0.5 min respectively at 100 mg/mL, with the ethyl acetate fraction being the most potent. GC–MS profiling identified key bioactive phytoconstituents including hexadecanamide, oleamide, and 1-heptacosanol—compounds known to disrupt membrane integrity, induce oxidative stress, and interfere with neuromuscular function. Molecular docking showed moderate binding affinity to β-tubulin, while molecular dynamics simulations revealed short-lived protein-ligand interactions, suggesting a non-exclusive tubulin targeting mechanism. The rapid anthelmintic response, combined with effects among fatty acid amides, sterols, and phenolics, suggests a multifactorial mode of action. These results support the traditional use of C. penduliflorus and underscore its stem bark as a promising source of synergistically acting lead compounds for novel anthelmintic drug development.