ReferenceID 3600

Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection

J Antimicrob Chemother

OBJECTIVES: The aim of the present study was to characterize glycyrrhizic acid (GA) and assess its immunomodulatory potential in a model of experimental visceral leishmaniasis. METHODS: The antileishmanial activity of GA

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Reference Id
3600
Evidence Id
20190
Core Evidence Id
20190
Source Reference Id
496
Herb2 Reference Id
HBREF000840
Subject Paper Key
HBIN028190_22589456
Pubmed Id
22589456
Doi
10.1093/jac/dks159
Paper Title
Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection
Paper Abstract
OBJECTIVES: The aim of the present study was to characterize glycyrrhizic acid (GA) and assess its immunomodulatory potential in a model of experimental visceral leishmaniasis. METHODS: The antileishmanial activity of GA was tested in an amastigote-macrophage model and its non-cytotoxic dose was measured by a cell viability assay. To understand the effector mechanism of GA-treated macrophages against leishmanial parasites, real-time PCR analysis of inducible nitric oxide synthase 2 (iNOS2) was carried out followed by measurement of nitric oxide generation by Griess reagent. The effect of GA on the production of cytokines, such as interleukin (IL)-12, tumour necrosis factor (TNF)-α, IL-10 and transforming growth factor (TGF)-β, was measured by ELISA (protein) and real-time PCR. The expression of iNOS2 and cyclooxygenase-2 (Cox-2) was studied by western blotting. The parasite burden of the liver and spleen following GA treatment was determined by the stamp-smear method, and T cell proliferation was assessed via [ H]thymidine uptake, measured by a liquid scintillation counter. RESULTS: Results showed that GA treatment caused an enhanced expression of iNOS2 along with inhibition of Cox-2 in Leishmania donovani-infected macrophages. GA treatment in infected macrophages enhanced the expression of IL-12 and TNF-α, concomitant with a down-regulation of IL-10 and TGF-β. GA increased macrophage effector responses via inhibition of Cox-2-mediated prostaglandin E2 release in L. donovani-infected macrophages. GA also decreased hepatic and splenic parasite burden and increased T cell proliferation in Leishmania-infected BALB/c mice. CONCLUSIONS: These results provide a mechanistic understanding of GA-mediated protection against leishmanial parasites within the host.
Journal
J Antimicrob Chemother
Publish Year
2012
Experiment Subject
macrophages,balb/c mice
Experiment Type
Animal & Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Glycyrrhizic acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani infection
Bilingual Status
semi_complete