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Asiaticoside Induces Tumour-Necrosis-Factor-a-Mediated Nitric Oxide Production to Cure Experimental Visceral Leishmaniasis caused by Antimony-Susceptible and -Resistant Leishmania Donovani Strains

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Title Asiaticoside Induces Tumour-Necrosis-Factor-a-Mediated Nitric Oxide Production to Cure Experimental Visceral Leishmaniasis caused by Antimony-Susceptible and -Resistant Leishmania Donovani Strains
 
Creator Bhaumik, Siddhartha Kumar
Paul, Joydeep
Naskar, Kshudiram
Karmakar, Subir
De, Tripti
 
Subject Infectious Diseases and Immunology
 
Description The aim of this study was to investigate and characterize the efficacy of asiaticoside in an experimental
model of visceral leishmaniasis caused by antimony-susceptible (AG83) and -resistant (GE1F8R and
K39) Leishmania donovani.
The effect of asiaticoside was evaluated by microscopic counting of intracellular amastigotes in
cultured macrophages stained with Giemsa. The antileishmanial effect of the compounds was assessed in
infected BALB/c mice by estimation of splenic and liver parasite burdens in Leishman Donovan units. Cytokines
were measured by real-time PCR and ELISA. Intracellular tumour necrosis factor-a (TNF-a) was measured by
fluorescence-activated cell sorting. Nitric oxide was measured by the Griess reaction.
Besides effectively inhibiting in vitro replication of the parasite within macrophages, asiaticoside treatment
resulted in almost complete clearance of the liver and splenic parasite burden when administered at a
dose of 5 mg/kg×10 starting on day +30 of challenge with antimony-susceptible (AG83) and -resistant
(GE1F8R and K39) L. donovani. Asiaticoside treatment was associated with a switch in the host from a Th2-
to a Th1-type immune response accompanied by the induction of TNF-a-mediated nitric oxide production,
all of which are important elements for macrophage function in antileishmanial defence mechanisms.
These results suggest that oral therapy with asiaticoside shows promising antileishmanial efficacy
in animals infected by antimony-susceptible (AG83) and -resistant (GE1F8R and K39) L. donovani.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1513/1/JOURNAL_OF_ANTIMICROBIAL_CHEMOTHERAPY__67(_4)_910%2D920;2012[32].pdf
Bhaumik, Siddhartha Kumar and Paul, Joydeep and Naskar, Kshudiram and Karmakar, Subir and De, Tripti (2012) Asiaticoside Induces Tumour-Necrosis-Factor-a-Mediated Nitric Oxide Production to Cure Experimental Visceral Leishmaniasis caused by Antimony-Susceptible and -Resistant Leishmania Donovani Strains. Journal of Antimicrobial Chemotherapy, 67 (4). pp. 910-920.
 
Relation http://dx.doi.org/10.1093/jac/dkr575
http://www.eprints.iicb.res.in/1513/