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SummaryWithania 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 offer 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 pre‐treatment 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‐γ, and 128R increased levels of IL‐4. Taken together, our findings reveal potential immunoprophylactic properties of Withania somnifera and further studies are needed to ascertain the benefits of this plant against other pathogens as well.© 2011 Blackwell Publishing Ltd

The immunoprophylactic and therapeutic potentials of root extracts of Withania somnifera chemotypes (NMITLI-118, NMITLI-101) and pure withanolide-withaferin A was investigated against Leishmania donovani infection in hamsters. The naive animals, fed orally with immunostimulatory doses of chemotypes 101R, 118R (10 and 3 mg/kg) and withaferin A (9 and 3 mg/kg) for five consecutive days and challenged with Leishmania parasites on day 6, were euthanized on days 30 and 45 p.c. for the assessment of parasite clearance, real-time analysis of mRNAs of Th1/Th2 cytokines (IFN-γ, IL-12, TNF-α, iNOS/IL-4, IL-10 and TGF-β), NO production, reactive oxygen species (ROS) generation, lymphocyte transformation test and antibody responses. By day 45 p.c., there was a significant increase in the mRNA expression of iNOS, IFN-γ, IL-12 and TNF-α but decrease in IL-4, IL-10 and TGF-β, an enhanced Leishmania-specific LTT response as well as ROS, NO and antileishmanial IgG2 levels in 101R-treated hamsters followed by 118R- and withaferin A-treated ones, respectively. When these chemotypes were given to L. donovani-infected hamsters at different doses, there was moderate therapeutic efficacy of chemotype 101R (~50%) at 30 mg/kg × 5 followed by the other two. The results established that the 101R is the most potential chemotype and can be evaluated for combination therapy along with available antileishmanials.

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