Deciphering the actions of essential oils in C. elegans as novel tools for anthelmintic therapy

Abstract

Essential Oils (EOs), plant extracts and herbal preparations have been extensively applied for human and veterinary health; their active agents have been isolated and incorporated into many current pharmaceutical preparations. Our hypothesis is that EOs of aromatic plants used for aromatherapy or food additives include compounds with anthelmintic activity and we test it using Caenorhabditis elegans as a model of parasitic nematodes. We developed behavioral and molecular assays in wild-type and mutant worms lacking receptors involved in locomotion to identify the main compounds of EOs mediating anthelmintic activities and their pharmacological targets. We also explored the combination of current anthelmintics with EOs’ active compounds as a strategy to reduce drug resistance. Our goal is to provide a powerful platform for discovery of new antiparasitic compounds. We found six different EOs that inhibit C. elegans locomotion and egg hatching with different potencies, indicating their anthelmintic capacity, and identified the main bioactive compounds and receptor targets. Through single-channel and whole-cell recordings from C. elegans muscle cultured cells we determined that C. elegans L-AChRs and GABA receptors are modulated by these compounds and revealed their molecular mechanisms. Our results propose EOs as sources of natural compounds with promising polypharmacological profiles for anthelmintic therapies, decipher the molecular basis of their actions, and provide information about the efficacy of drug combinations that emerge as strategies to reduce drug resistance in nematodes.