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Kaurenoic Acid Possesses Leishmanicidal Activity by Triggering a NLRP12/IL-1ß/cNOS/NO Pathway.
Miranda, Milena Menegazzo; Panis, Carolina; da Silva, Suelen Santos; Macri, Juliana Aparecida; Kawakami, Natalia Yoshie; Hayashida, Thiago Hideki; Madeira, Tiago Bervelieri; Acquaro, Vinicius Ricardo; Nixdorf, Suzana Lucy; Pizzatti, Luciana; Ambrósio, Sérgio Ricardo; Cecchini, Rubens; Arakawa, Nilton Syogo; Verri, Waldiceu Aparecido; Costa, Ivete Conchon; Pavanelli, Wander Rogério.
Afiliação
  • Miranda MM; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Panis C; Laboratory of Inflammatory Mediators, State University of Western Parana, 85605-010 Francisco Beltrão, PR, Brazil.
  • da Silva SS; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Macri JA; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Kawakami NY; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Hayashida TH; Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Madeira TB; Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Acquaro VR; Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Nixdorf SL; Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Pizzatti L; Department of Biochemistry, Federal University of Rio de Janeiro, 21941-909 Rio de Janeiro, RJ, Brazil.
  • Ambrósio SR; Nucleus of Research in Exact and Technological Sciences, University of Franca, 14404-600 Franca, SP, Brazil.
  • Cecchini R; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Arakawa NS; Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Verri WA; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Costa IC; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
  • Pavanelli WR; Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil.
Mediators Inflamm ; 2015: 392918, 2015.
Article em En | MEDLINE | ID: mdl-26074677
Leishmania amazonensis (L. amazonensis) infection can cause severe local and diffuse injuries in humans, a condition clinically known as American cutaneous leishmaniasis (ACL). Currently, the therapeutic approach for ACL is based on Glucantime, which shows high toxicity and poor effectiveness. Therefore, ACL remains a neglected disease with limited options for treatment. Herein, the in vitro antiprotozoal effect and mechanisms of the diterpene kaurenoic acid [ent-kaur-16-en-19-oic acid] (KA) against L. amazonensis were investigated. KA exhibited a direct antileishmanial effect on L. amazonensis promastigotes. Importantly, KA also reduced the intracellular number of amastigote forms and percentage of infected peritoneal macrophages of BALB/c mice. Mechanistically, KA treatment reestablished the production of nitric oxide (NO) in a constitutive NO synthase- (cNOS-) dependent manner, subverting the NO-depleting escape mechanism of L. amazonensis. Furthermore, KA induced increased production of IL-1ß and expression of the inflammasome-activating component NLRP12. These findings demonstrate the leishmanicidal capability of KA against L. amazonensis in macrophage culture by triggering a NLRP12/IL-1ß/cNOS/NO mechanism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania mexicana / Macrófagos Peritoneais / Peptídeos e Proteínas de Sinalização Intracelular / Diterpenos / Interleucina-1beta / Óxido Nítrico / Antiprotozoários Limite: Animals Idioma: En Revista: Mediators Inflamm Assunto da revista: BIOQUIMICA / PATOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania mexicana / Macrófagos Peritoneais / Peptídeos e Proteínas de Sinalização Intracelular / Diterpenos / Interleucina-1beta / Óxido Nítrico / Antiprotozoários Limite: Animals Idioma: En Revista: Mediators Inflamm Assunto da revista: BIOQUIMICA / PATOLOGIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos