title: Resveratrol is active against Leishmania amazonensis: in vitro effect of its association with Amphotericin B.
abstract: Resveratrol is a polyphenol found in black grapes and red wine and has many biological activities. In this study, we evaluated the effect of resveratrol alone and in association with amphotericin B (AMB) against Leishmania amazonensis. Our results demonstrate that resveratrol possesses both antipromastigote and antiamastigote effects, with 50% inhibitory concentrations (IC50s) of 27 and 42 μM, respectively. The association of resveratrol with AMB showed synergy for L. amazonensis amastigotes, as demonstrated by the mean sums of fractional inhibitory index concentration (mean ΣFIC) of 0.483, although for promastigotes, this association was indifferent. Treatment with resveratrol increased the percentage of promastigotes in the sub-G0/G1 phase of the cell cycle, reduced the mitochondrial potential, and showed an elevated choline peak and CH2-to-CH3 ratio in the nuclear magnetic resonance (NMR) spectroscopy analysis; all these features indicate parasite death. Resveratrol also decreased the activity of the enzyme arginase in uninfected and infected macrophages with and without stimulation with interleukin-4 (IL-4), also implicating arginase inhibition in parasite death. The anti-Leishmania effect of resveratrol and its potential synergistic association with AMB indicate that these compounds should be subjected to further studies of drug association therapy in vivo.
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christian
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Deivid Costa
authors.initials: DC
authors.lastname: Soares
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Michelle Tanny Cunha do
authors.initials: MT
authors.lastname: Nascimento
authors.affiliation: Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropédica, Rio de Janeiro, Brazil.
authors.forename: Lucia Helena
authors.initials: LH
authors.lastname: Pinto-da-Silva
authors.affiliation: Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carolina Galvão
authors.initials: CG
authors.lastname: Sarzedas
authors.affiliation: Núcleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luzineide Wanderley
authors.initials: LW
authors.lastname: Tinoco
authors.affiliation: Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil esaraiva@micro.ufrj.br.
authors.forename: Elvira Maria
authors.initials: EM
authors.lastname: Saraiva
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology; D019295:Computational Biology; D004357:Drug Synergism; D007891:Leishmania / Q000187:drug effects* / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D000077185:Resveratrol; D012310:Ristocetin / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D013267:Stilbenes; D012310:Ristocetin; D000666:Amphotericin B; D000077185:Resveratrol
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