Asiaticoside induces tumour-necrosis-factor-α-mediated nitric oxide production to cure experimental visceral leishmaniasis caused by antimony-susceptible and -resistant Leishmania donovani strains.
J Antimicrob Chemother
; 67(4): 910-20, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22258930
ABSTRACT
OBJECTIVES:
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.METHODS:
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-α (TNF-α) was measured by fluorescence-activated cell sorting. Nitric oxide was measured by the Griess reaction.RESULTS:
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-α-mediated nitric oxide production, all of which are important elements for macrophage function in antileishmanial defence mechanisms.CONCLUSIONS:
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Triterpenos
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Leishmania donovani
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Factor de Necrosis Tumoral alfa
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Leishmaniasis Visceral
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Óxido Nítrico
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Antiprotozoarios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2012
Tipo del documento:
Article
País de afiliación:
India