Deciphering molecular targets and mechanisms of action of essential oils in Caenorhabditis elegans as a strategy for anthelmintic drug discovery

HERNANDO, G.; TURANI, O.; BOUZAT, C.B.

Rosario

Encuentro; 2nd Latin American Worm Meeting; 2020

Essential oils (EOs) are natural products produced by aromatic plants. EOs are secondary metabolites important for plant defense mechanism. They have been widely used in traditional medicine due to their antioxidant, antimicrobial, antifungal and anthelmintic activities. Parasitic nematodes are of major significance as human pathogens and have important economic impact worldwide due to considerable losses in livestock and food crops. Drug treatment of nematode infections are the pillar of worm control in human and veterinary medicine. Due to the appearance of drug resistant nematodes, there is a need of developing novel drugs. As parasitic nematodes aren?t ideal laboratory animals, the non-parasitic nematode Caenorhabditis elegans, has emerged as a model organism for drug discovery. We used paralysis assays of wild-type and mutant C. elegans strains to identify EOs with potential anthelmintic activities, revealed the active components, the molecular targets and mechanisms of action. We found that EOs produced rapid paralysis of C. elegans and we established the EC50 values between 0.02-1.2 percent of EOs. We also found that all EOs inhibit egg hatching. Thereby, EOs can mediate both rapid and long-term anthelmintic effects. In this way, we determined that trans-cinnamaldehyde (TC), a major component of C. verum EOs, produced both paralysis and egg-hatching inhibition, therefore revealing that TC is an active component of C. verum. By testing mutant worms, we identified that muscle L-AChR, N-AChR and GABA receptors are EOs and TC targets in vivo. Thus, by modulating two types of receptors with key roles in worm motility, EOs emerge as novel sources of anthelmintic compounds.