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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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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 |
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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 |
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