Plant-derived anthelmintic agents in veterinary helminth control: Mechanistic insights and translational challenges

Helminth infections, caused by cestodes, nematodes, and trematodes, continue to be a major constraint on animal health, livestock productivity, and global parasite control. While conventional anthelmintics such as benzimidazoles, macrocyclic lactones, levamisole, praziquantel, and triclabendazole are highly effective, their extensive use has driven resistance development, revealed stage-specific efficacy limitations, and raised concerns regarding environmental residues. These limitations have renewed interest in plant-derived anthelmintic agents as potential pharmacological leads and complementary tools in integrated parasite management strategies. This review synthesizes current experimental evidence on medicinal plants and phytochemicals with activity against major helminth taxa, integrating mechanistic insights with comparative efficacy and translational relevance. Across helminths, plant-derived compounds exert multi-target effects, including tegumental or cuticular disruption, modulation of Ca²⁺ homeostasis, mitochondrial dysfunction, oxidative stress induction, neuromuscular impairment, and suppression of parasite fecundity. In vivo studies typically report fecal egg count reduction (FECR) values of approximately 30-85% for crude extracts, whereas conventional drugs frequently exceed 95% efficacy at lower doses. Despite promising in vitro and experimental findings, translation into consistent systemic efficacy remains limited. Key challenges include insufficient phytochemical standardization, variability in extraction methodologies, supraphysiological in vitro dosing, limited pharmacokinetic characterization, and a lack of controlled trials in naturally infected target species. Overall, plant-derived anthelmintics should be regarded as mechanistically diverse pharmacological leads rather than direct substitutes for synthetic drugs. Future progress will require standardized chemistry, molecular validation, pharmacokinetic profiling, and robust field-based studies to support their integration into veterinary practice.