Kaurenoic Acid Possesses Leishmanicidal Activity by Triggering a NLRP12/IL-1β/cNOS/NO Pathway

Milena Menegazzo Miranda; Carolina Panis; Suelen Santos da Silva; Juliana Aparecida Macri; Natalia Yoshie Kawakami; Thiago Hideki Hayashida; Tiago Bervelieri Madeira; Vinicius Ricardo Acquaro; Suzana Lucy Nixdorf; Luciana Pizzatti; Sérgio Ricardo Ambrósio; Rubens Cecchini; Nilton Syogo Arakawa; Waldiceu Aparecido Verri; Ivete Conchon Costa; Wander Rogério Pavanelli

doi:10.1155/2015/392918

Mediators of Inflammation (Jan 2015)

Kaurenoic Acid Possesses Leishmanicidal Activity by Triggering a NLRP12/IL-1β/cNOS/NO Pathway

Milena Menegazzo Miranda,
Carolina Panis,
Suelen Santos da Silva,
Juliana Aparecida Macri,
Natalia Yoshie Kawakami,
Thiago Hideki Hayashida,
Tiago Bervelieri Madeira,
Vinicius Ricardo Acquaro,
Suzana Lucy Nixdorf,
Luciana Pizzatti,
Sérgio Ricardo Ambrósio,
Rubens Cecchini,
Nilton Syogo Arakawa,
Waldiceu Aparecido Verri,
Ivete Conchon Costa,
Wander Rogério Pavanelli

Affiliations

Milena Menegazzo Miranda: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Carolina Panis: Laboratory of Inflammatory Mediators, State University of Western Parana, 85605-010 Francisco Beltrão, PR, Brazil
Suelen Santos da Silva: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Juliana Aparecida Macri: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Natalia Yoshie Kawakami: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Thiago Hideki Hayashida: Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Tiago Bervelieri Madeira: Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Vinicius Ricardo Acquaro: Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Suzana Lucy Nixdorf: Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Luciana Pizzatti: Department of Biochemistry, Federal University of Rio de Janeiro, 21941-909 Rio de Janeiro, RJ, Brazil
Sérgio Ricardo Ambrósio: Nucleus of Research in Exact and Technological Sciences, University of Franca, 14404-600 Franca, SP, Brazil
Rubens Cecchini: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Nilton Syogo Arakawa: Department of Chemistry, Center of Exact Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Waldiceu Aparecido Verri: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Ivete Conchon Costa: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil
Wander Rogério Pavanelli: Department of Pathological Sciences, Center of Biological Sciences, State University of Londrina, 86057-970 Londrina, PR, Brazil

DOI: https://doi.org/10.1155/2015/392918
Journal volume & issue: Vol. 2015

Abstract

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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-1β 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-1β/cNOS/NO mechanism.

Published in Mediators of Inflammation

ISSN: 0962-9351 (Print); 1466-1861 (Online)
Publisher: Wiley
Country of publisher: United Kingdom
LCC subjects: Medicine: Pathology
Website: https://onlinelibrary.wiley.com/journal/4792

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