Efficacy of Withania somnifera chemotypes NMITLI - 101R, 118R and Withaferin A against experimental visceral leishmaniasis.

Abstract

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.

• Authors: C D P Tripathi, R Gupta, P K Kushawaha, C Mandal, S Misra Bhattacharya, A Dube
• Journal: Parasite immunology (Parasite Immunol) Vol. 36 Issue 6 Pg. 253-65 (Jun 2014) ISSN: 1365-3024 [Electronic] England
• PMID: 24830833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Cytokines
• Immunoglobulin G
• Plant Extracts
• Withanolides
• withaferin A

Topics

• Animals
• Antibody Formation
• Cricetinae
• Cytokines (immunology)
• Immunoglobulin G (metabolism, therapeutic use)
• Leishmania donovani (growth & development)
• Leishmaniasis, Visceral (drug therapy, immunology, prevention & control)
• Male
• Plant Extracts (administration & dosage, therapeutic use)
• Plant Roots (chemistry)
• Th1 Cells (immunology)
• Withania (chemistry)
• Withanolides (therapeutic use)