ReferenceID 5300
Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2
J Antimicrob Chemother
OBJECTIVES: To evaluate the antileishmanial efficacy of genipin, which specifically inhibits uncoupling protein 2 (UCP2) that is induced in leishmaniasis to neutralize reactive oxygen species (ROS). METHODS: The effect o
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Record Fields
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- Reference Id
- 5300
- Evidence Id
- 21890
- Core Evidence Id
- 21890
- Source Reference Id
- 3857
- Herb2 Reference Id
- HBREF004654
- Subject Paper Key
- HBIN027445_32995849
- Pubmed Id
- 32995849
- Doi
- 10.1093/jac/dkaa406
- Paper Title
- Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2
- Paper Abstract
- OBJECTIVES: To evaluate the antileishmanial efficacy of genipin, which specifically inhibits uncoupling protein 2 (UCP2) that is induced in leishmaniasis to neutralize reactive oxygen species (ROS). METHODS: The effect of genipin was assessed against intracellular parasites in cultured macrophages and in suppressing spleen and liver parasite burdens in a BALB/c mouse model of visceral leishmaniasis by microscopic evaluation of intracellular amastigotes stained with Giemsa. ROS and mitochondrial membrane potential were measured by H2DCFDA- and JC-1-based fluorometric analysis. ELISA was performed for various Th1 and Th2 cytokines in both in vitro and in vivo infected conditions to evaluate the type of immunological responses. The role of UCP2 was assessed by lipofectamine-mediated transfection and overexpression in macrophages and short hairpin RNA-mediated knockdown of UCP2 in infected animals. RESULTS: Genipin reduced the infection-induced UCP2 levels in macrophages, with optimum effect at 100 muM. Genipin reversed parasite-induced ROS suppression and mitochondrial membrane potential disruption. It has no inhibitory effect on promastigote or axenic amastigote forms, but markedly suppressed amastigote multiplication within macrophages, which was reversed by the ROS scavenger N-acetyl cysteine. Genipin administration (30 mg/kg/day) in infected mice showed significant suppression of liver and spleen parasite burdens with an enhanced host-favourable cytokine balance in a ROS-p38 mitogen-activated protein kinase-dependent manner. Co-treatment with genipin plus a sublethal dose of sodium antimony gluconate (SAG50) showed almost a curative reduction in spleen and liver parasite burden. CONCLUSIONS: These results suggest the effectiveness of genipin as a synergistic agent for the front-line antileishmanial drug SAG in circumventing the resistance and toxicity problems associated with its high curative dose.
- Journal
- J Antimicrob Chemother
- Publish Year
- 2021
- Experiment Subject
- mouse; cultured macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Visceral Leishmaniasis; Leishmaniasis
- Paper Title Cn
- Paper Title En
- Antileishmanial effect of the natural immunomodulator genipin through suppression of host negative regulatory protein UCP2
- Bilingual Status
- semi_complete