Cargando…

Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosa...

Descripción completa

Detalles Bibliográficos
Autores principales: Conte, Fernando P., Ferraris, Fausto K., Costa, Thadeu E. M. M., Pacheco, Patricia, Seito, Leonardo N., Verri, Waldiceu A., Cunha, Fernando Q., Penido, Carmen, Henriques, Maria G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272452/
https://www.ncbi.nlm.nih.gov/pubmed/25654532
http://dx.doi.org/10.3390/molecules20022636
_version_ 1783377160019378176
author Conte, Fernando P.
Ferraris, Fausto K.
Costa, Thadeu E. M. M.
Pacheco, Patricia
Seito, Leonardo N.
Verri, Waldiceu A.
Cunha, Fernando Q.
Penido, Carmen
Henriques, Maria G.
author_facet Conte, Fernando P.
Ferraris, Fausto K.
Costa, Thadeu E. M. M.
Pacheco, Patricia
Seito, Leonardo N.
Verri, Waldiceu A.
Cunha, Fernando Q.
Penido, Carmen
Henriques, Maria G.
author_sort Conte, Fernando P.
collection PubMed
description Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB(4), PGE(2), TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations.
format Online
Article
Text
id pubmed-6272452
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62724522018-12-13 Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice Conte, Fernando P. Ferraris, Fausto K. Costa, Thadeu E. M. M. Pacheco, Patricia Seito, Leonardo N. Verri, Waldiceu A. Cunha, Fernando Q. Penido, Carmen Henriques, Maria G. Molecules Article Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 μg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005–5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB(4), PGE(2), TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations. MDPI 2015-02-03 /pmc/articles/PMC6272452/ /pubmed/25654532 http://dx.doi.org/10.3390/molecules20022636 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Conte, Fernando P.
Ferraris, Fausto K.
Costa, Thadeu E. M. M.
Pacheco, Patricia
Seito, Leonardo N.
Verri, Waldiceu A.
Cunha, Fernando Q.
Penido, Carmen
Henriques, Maria G.
Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title_full Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title_fullStr Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title_full_unstemmed Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title_short Effect of Gedunin on Acute Articular Inflammation and Hypernociception in Mice
title_sort effect of gedunin on acute articular inflammation and hypernociception in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6272452/
https://www.ncbi.nlm.nih.gov/pubmed/25654532
http://dx.doi.org/10.3390/molecules20022636
work_keys_str_mv AT contefernandop effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT ferrarisfaustok effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT costathadeuemm effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT pachecopatricia effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT seitoleonardon effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT verriwaldiceua effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT cunhafernandoq effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT penidocarmen effectofgeduninonacutearticularinflammationandhypernociceptioninmice
AT henriquesmariag effectofgeduninonacutearticularinflammationandhypernociceptioninmice