Withania somnifera chemotypes NMITLI 101R, NMITLI 118R, NMITLI 128R and withaferin A protect Mastomys coucha from Brugia malayi infection

Withania somnifera is an ayurvedic Indian medicinal plant whose immunomodulatory activities have been widely used as a home remedy for several ailments. We recently observed immunostimulatory properties in the root extracts of chemotypes NMITLI-101, NMITLI-118, NMITLI-128 and pure withanolide, withaferin A. In the present study, we evaluated the potential immunoprophylactic efficacies of these extracts against an infective pathogen. Our results show that administration of aqueous ethanol extracts (10 mg/kg) and withaferin A (0.3 mg/kg), 7 days before and after challenge with human filarial parasite Brugia malayi, offers differential protection in Mastomys coucha with chemotype 101R offering best protection (53.57%) as compared to other chemotypes. Our findings also demonstrate that establishment of B.malayi larvae was adversely affected by pretreatment with withaferin A as evidenced by 63.6% reduction in adult worm establishment. Moreover, a large percentage of the established female worms (66.2%) also showed defective embryogenesis. While the filaria-specific immunological response induced by withaferin A and NMITLI-101 showed a mixed Th1/Th2 phenotype, 118R stimulated production of IFN-gamma and 128R increased levels of IL-4. Taken together, our findings reveal potential immunoprophylactic properties of W.somnifera, and further studies are needed to ascertain the benefits of this plant against other pathogens as well.