Targeting the nervous system of the parasitic worm, Haemonchus contortus, with quercetin.

Abstract

High Prevalence of infection rate, limited choice of drugs and emerging resistance against these leads to an pressing need for the development of new antihelminthic drugs and drug targets. However, limited understanding of the physiology of worms has delayed the process substantially. Here, for the first time, we are reporting the tissue morphology of Haemonchus contortus, and target its nervous system with a quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all developmental stages of the nematode. Histological analysis demonstrated damage of various body parts including isthmus, brut, pseudocoele, and other organs. Mechanistic studies revealed the generation of oxidative stress and alteration of the stress response enzyme activities. Importantly, the time-dependent imaging of ROS-generation revealed the neuronal system as the primary target of quercetin in the adult worms, which eventually leads to the paralysis and death of the worms. This work demonstrates neuronal system as a novel drug target for quercetin. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/451932v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@9204caorg.highwire.dtl.DTLVardef@789005org.highwire.dtl.DTLVardef@1375539org.highwire.dtl.DTLVardef@1bc4c47_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract Schematic representation showing generation of Reactive Oxygen Stress in the nervous system of H. contortus due to quercetin treatment. C_FIG