INVESTIGADORES
BOUZAT Cecilia Beatriz
congresos y reuniones científicas
Título:
Biological activities of essential oils on Caenorhabditis elegans: from molecular targets to anthelmintic therapeutic strategies
Autor/es:
HERNANDO G.; TURANI, O.; RODRIGUEZ ARAUJO, N.; BOUZAT, C.
Reunión:
Congreso; 24TH International C. elegans Conference; 2023
Resumen:
Plants, herbal preparations and essential oils are used for health and medical functions since ancient times. Essential oils(EOs) have been extensively applied for human and veterinary health; their active agents have been isolated and incorporatedinto many current pharmaceutical preparations. Our study involves the use of Caenorhabditis elegans as a model of parasiticnematodes due to its simplicity and easy maintenance in the laboratory. We start from the hypothesis that EOs of aromaticplants used for aromatherapy or as food additives have anthelmintic action. We developed behavioral and molecular assays inwild-type worms, and analyzed mutant strains lacking receptors involved in locomotion to identify the pharmacological targetsmediating the anthelmintic activities. We also explored the combination of current anthelmintics together with the additionof EOs purified compounds as a strategy to reduce resistance. In paralysis assays on agar plates, all tested EOs inhibited withdifferent potencies C. elegans locomotion as well as egg hatching. The major compounds present in the tested EOs, transcinnamaldehyde(TC), geraniol, citronellol and linalool, were active at C. elegans. The combination of TC with the commercialanthelmintics levamisole and monepantel showed synergistic paralysis effects, while its combination with piperazine orivermectin produced antagonic effects. Mutant worms lacking the levamisole-sensitive nicotinic receptor (L-AChR), GABA andglutamate receptors were partially resistant to these compounds. By single-channel recordings from C. elegans muscle culturedcells we deciphered how L-AChRs are modulated by TC. The analysis revealed that TC acts as an allosteric inhibitor of L-AChRswith key roles in nematode locomotion. Overall, we identified essential oils and their components as novel anthelmintic drugsand revealed their main pharmacological targets. Our results propose EOs as sources of natural compounds with promisingpolypharmacological profiles for anthelmintic therapeutics, and provide data on the efficacies of combinations that emerge asstrategies to reduce drug resistance in nematodes.