In vitro anthelmintic effect of anacardic acid and ivermectin, individually and in combination, against Haemonchus...

Resistance to conventional anthelmintics in populations of Haemonchus contortus represents one of the main challenges for the control of haemonchosis in small ruminants. The combination of drugs with natural compounds emerges as a strategy to increase the effectiveness of anthelmintics. The present study evaluated the anthelmintic potential of anacardic acid (AA), a phenolic lipid derived from Anacardium occidentale, isolated and in combination with ivermectin (IVM), against H. contortus. The chemical characterization of AA was performed by high-performance liquid chromatography. Anthelmintic activity was evaluated using larval development tests (LDT), larval migration inhibition test (LMIT), adult worm motility test (AWMT), and the interaction between compounds was determined by the Chou-Talalay and Tallarida methods. Acute oral toxicity was evaluated in mice. In larval stages, the AA:IVM combination reduced effective concentration values compared to isolated treatments, indicating a synergistic interaction. In adult nematodes, the combination showed greater inhibition of motility with synergistic effects for most comparisons regardless of the method used for combination analysis. In mice, the isolated compounds did not show toxicity at studied levels. However, co-administration resulted in dose-dependent toxicity, with 50% lethal dose (LD₅₀) at 1564 mg of AA/kg + 2.47 mg of IVM/kg, probably associated with increased systemic exposure and greater penetration into the central nervous system. These results indicate synergistic activity of the AA and IVM combination against H. contortus but also a level of toxicity that should be considered in future in vivo test.