ESSENTIAL OILS FOR THE DISCOVERY OF NEW ANTHELMINTIC COMPOUNDS TESTED ON THE NEMATODE CAENORHABDITIS ELEGANS

HERNANDO GUILLERMINA; TURANI ORNELLA; BOUZAT CECILIA

Mar del Plata-SCIENTIFIC AWARDS SESSIONS-Asistencia virtual

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020 LXV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FISIOLOGÍA (SAFIS); 2020

SAIC, SAI, SAFIS

SCIENTIFIC AWARDS SESSIONS-SAIC - LEÓN CHERNY AWARD-Parasitic nematodes of humans and animals cause diseases of major socio-economic importance globally. Control of infections in both human and veterinary medicinecurrently relies mainly on chemotherapy, but resistanceis an increasing problem, so there is an urgent need fordiscovery of novel drugs. As parasitic nematodes are notideal laboratory animals, the free-living nematode C. elegans was demonstrated to be an excellent model systemfor the discovery of new anthelmintics and for characterizing their mechanisms of action and resistance. Essential oils (EOs) are natural products produced by aromaticplants. EOs are complex mixtures that contain 2 or 3 major phytochemicals, which can be terpenes or aromaticcompounds. We used paralysis assays of wild-type andmutant C. elegans strain to identify EOs with potentialanthelmintic activities, reveal the active components,the target sites and the mechanisms of action. We foundthat EOs belonging to six different orders produced rapid paralysis of C. elegans and we established the halfmaximal effective concentration values between 0.02-1.2percent of EOs. All EOs tested also inhibited egg hatching, a property related to anthelmintic ability. Thus, EOsmediate both rapid and long-term anthelmintic effects.We determined that trans-cinnamaldehyde (TC), a major component of C. verum EO, produces both paralysisand egg-hatching inhibition. By testing mutant worms,we identified the muscle L-AChR and GABA receptorsas EOs and TC targets in vivo. Thus, by modulating tworeceptors with key roles in worm motility, these EOsemerge as novel sources of anthelmintic compounds.Likewise, the N-AChR mutant strain is slightly resistantto TC, thus revealing a third target receptor for terpenes.Due to the potential of EOs as sources of novel antiparasitic compounds, additional studies will be carried out todetermine in more detail the molecular mechanisms ofaction and structure-activity relationships of their activecompounds.