New insights into the molecular mechanism of natural products against helminthiasis

Natural products represent a valuable resource for the treatment of infectious diseases and for the development of antiinfective drugs. With respect to soil-transmitted helminthiasis, especially tanniferous plants have been proposed as a sustainable control of parasitic nematodes to overcome the problem of resistances to standard anthelmintics in livestock [1,2]. Our studies focused on the anthelmintic activity of plant extracts from traditional West African medicine. In particular, a hydroethanolic extract from the leaves of Combretum mucronatum Schumach. & Thonn. (CM) inhibited larval migration in vitro in a panel of animal parasitic nematodes. Oligomeric procyanidins were phytochemically characterized and identified as the active constituents of the extract. An in vivo study in goats infected with Haemonchus contortus further supported the anthelmintic potential of CM. Subsequent functional investigations that were carried out in the free-living nematode Caenorhabditis elegans revealed the cuticle as the main binding site for tannins. An increased rigidity of the cuticle was measured and could explain the inhibition of larval molting as well as a decrease in the motility of adult worms. In addition, the transcriptomic reponse to treatement with CM indicated the presence of unique proline-rich proteins that may represent a mechanism for tannin defense in the nematode. In summary, CM showed promising activities against animal parasitic nematodes, underlining the potential of tanniferous plant extracts against soil-transmitted helminthiasis. Additionally, insights into the mode of action were gained by microscopy and molecular biology techniques.