Bio-guided isolation of a new sesquiterpene from Artemisia cina with anthelmintic activity against Haemonchus contortus L3 infective larvae

Abstract

Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production and presenting anthelmintic resistance, requiring alternative antiparasitic treatments, including the exploration of plant-based anthelmintics. Artemisia cina (Asteraceae) is a plant whose n-hexane (n-HE) and ethyl acetate extract (EAE) exhibits anthelmintic activity against H. contortus, being the n-HE more active. With the aim of discovering additional bioactive metabolites, a chemical analysis was performed on EAE, which presented a LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid, a new sesquiterpene that was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed a CL50 of 0.13 (0.11 -0.14) mg/mL and CL90 of 0.40 (0.37 - 0.44) mg/mL, which, compared with EAE larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with anthelmintic effects against H. contortus L3 infective larvae was isolated from the EAE of Artemisia cina. Author summaryHaemonchus contortus is a hematophagous gastrointestinal parasite that affects grazing sheep. Due to its feeding habits, it induces anemia, poor digestion, diarrhea, and weight loss in animals, potentially leading to death in young individuals and causing economic losses in animal production. Moreover, it demonstrates resistance to drugs, making it imperative to explore alternative antiparasitic treatments against H. contortus, such as the discovery and development of plant-based anthelmintics. In this work, we explore the ethyl acetate extract (EAE) of Artemisia cina in the search of bioactive compounds. A new sesquiterpene was separated through a bio-guided isolation monitoring the larvicidal effect against H. Contortus L3 infective larvae and was named cinic acid. These findings suggest that the EAE could be promising candidate for the development of a plant-based pharmaceutical preparation with notable anthelmintic activity against H. contortus.