Efficacy of Withania somnifera chemotypes NMITLI – 101R, 118R and Withaferin A against experimental visceral leishmaniasis. (June 2014)

• Record Type: Journal Article
• Authors: Tripathi, C. D. P.; Gupta, R.; Kushawaha, P. K.; Mandal, C.; Misra Bhattacharya, S.; Dube, A.
• Is Part Of: Parasite immunology. Volume 36:Number 6(2014:Jun.)
• Page Start: 253
• Page End: 265
• Publication Date: 2014-06
• Subjects: Veterinary parasitology -- Immunological aspects -- Periodicals; Host-parasite relationships -- Immunological aspects -- Periodicals; 571.96
• DOI: 10.1111/pim.12112
• Languages: English
• ISSNs: 0141-9838

Abstract

<abstract abstract-type="main" id="pim12112-abs-0001"> <title>Summary</title> <p>The immunoprophylactic and therapeutic potentials of root extracts of <italic>Withania somnifera</italic> chemotypes (NMITLI‐118, NMITLI‐101) and pure withanolide–withaferin A was investigated against <italic>Leishmania donovani</italic> 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 <italic>Leishmania</italic> 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 <italic>Leishmania‐</italic>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 <italic>L. donovani</italic>‐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.</p> </abstract>