{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T13:10:42Z","timestamp":1781788242881,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":132,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p><jats:italic>Leishmania amazonensis<\/jats:italic> (<jats:italic>L. amazonensis<\/jats:italic>) 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 <jats:italic>in vitro<\/jats:italic> antiprotozoal effect and mechanisms of the diterpene kaurenoic acid [<jats:italic>ent<\/jats:italic>\u2010kaur\u201016\u2010en\u201019\u2010oic acid] (KA) against <jats:italic>L. amazonensis<\/jats:italic> were investigated. KA exhibited a direct antileishmanial effect on <jats:italic>L. amazonensis<\/jats:italic> 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\u2010 (cNOS\u2010) dependent manner, subverting the NO\u2010depleting escape mechanism of <jats:italic>L. amazonensis<\/jats:italic>. Furthermore, KA induced increased production of IL\u20101<jats:italic>\u03b2<\/jats:italic> and expression of the inflammasome\u2010activating component NLRP12. These findings demonstrate the leishmanicidal capability of KA against <jats:italic>L. amazonensis<\/jats:italic> in macrophage culture by triggering a NLRP12\/IL\u20101<jats:italic>\u03b2<\/jats:italic>\/cNOS\/NO mechanism.<\/jats:p>","DOI":"10.1155\/2015\/392918","type":"journal-article","created":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T21:07:43Z","timestamp":1431551263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Kaurenoic Acid Possesses Leishmanicidal Activity by Triggering a NLRP12\/IL\u20101<i>\u03b2<\/i>\/cNOS\/NO Pathway"],"prefix":"10.1155","volume":"2015","author":[{"given":"Milena Menegazzo","family":"Miranda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Panis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suelen Santos","family":"da 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