Caenorhabditis elegans as a model for testing novel anthelmintic compounds isolated from plant extracts

FARAONI, M.B.; CASTRO, M.J.; BOUZAT, C.; BERGÉ, I.

Mar del Plata

Congreso; LXI Reunión Anual Soc Arg Inv Clínica (SAIC), LXIV Reunión Anual Soc Arg Inmunología (SAI), XLVIII Reunión Anual Soc Arg Farmacol Exp (SAFE), VII Reunión Anual Soc Arg Nanomedicina (NANOMEDar) y V Congreso Asoc Arg Ciencia y Tecnología de Animales de Lab; 2016

Parasitic nematodes affect human health as well as livestock and crops. Resistance to current anthelmintic drugs has prompted the search for new compounds. The use of parasitic worms for drug testing is costly and difficult. In contrast, the free-living nematode Caenorhabditis elegans has emerged as a valuable platform for the study of anthelmintic drugs. Considering that natural products provide a diverse and unique source of bioactive lead compounds for drug discovery, extracts of Diplotaxis tenuifolia and Thelesperma megapotamicum, and compounds isolated from their flowers and leaves were investigated for anthelmintic activity against C. elegans. From D. tenuifolia we isolated and identified by NMR a flavonol glycoside, isorhamnetin-3-O--D-glucoside (1), which is one of the main compounds of the ethyl acetate subfraction. By GC-MS analysis of the essential oil obtained from T. megapotamicum we revealed the qualitative and quantitative composition of the volatile compounds. The most abundant is limonene (2). Short- and long-term effects of these two compounds on anthelmintic activity were determined by evaluating the changes in locomotion, measured by the number of thrashes/min after a 10-min exposure, and the changes in larval growth. Neither compound affected the number of thrashes/min with respect to the control (~200/min). When compounds were added to the growth media, worms developed to the larval 4 stage with slightly reduced body size. However, larval development was severely impaired when the F1 generation was continuously treated with compound 1, whereas with compound 2 no significant changes were observed. Quercetin, an unglycosylated commercial flavonoid whose action at C. elegans has been tested previously, did not affect significantly larval growth. Our results propose that flavonol glycosides might provide a new class of anthelmintic drugs.