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2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms
2-Allylphenol (2-AP) is a synthetic phenylpropanoid, structurally related to cardanol, thymol, and ortho-eugenol. Phenylpropanoids are described in the literature as being capable of promoting biological activity. Due to the similarity between 2-AP and other bioactive phenylpropanoids, the present r...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462329/ https://www.ncbi.nlm.nih.gov/pubmed/31049124 http://dx.doi.org/10.1155/2019/1346878 |
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author | Aragão Neto, Humberto de Carvalho da Fonsêca, Diogo Vilar Braga, Renan Marinho Scotti, Marcus Tullius do Nascimento, Terezinha Weyne Araújo Borges Assis, Davidson Barbosa Rodrigues-Mascarenhas, Sandra Silva, Luiz Henrique Agra Cavalcante Galvão, José Guilherme Ferreira Marques Rocha, Hugo Alexandre Oliveira Vidal, Arthur Antunes Jacome Filho, José Maria Barbosa de Almeida, Reinaldo Nóbrega |
author_facet | Aragão Neto, Humberto de Carvalho da Fonsêca, Diogo Vilar Braga, Renan Marinho Scotti, Marcus Tullius do Nascimento, Terezinha Weyne Araújo Borges Assis, Davidson Barbosa Rodrigues-Mascarenhas, Sandra Silva, Luiz Henrique Agra Cavalcante Galvão, José Guilherme Ferreira Marques Rocha, Hugo Alexandre Oliveira Vidal, Arthur Antunes Jacome Filho, José Maria Barbosa de Almeida, Reinaldo Nóbrega |
author_sort | Aragão Neto, Humberto de Carvalho |
collection | PubMed |
description | 2-Allylphenol (2-AP) is a synthetic phenylpropanoid, structurally related to cardanol, thymol, and ortho-eugenol. Phenylpropanoids are described in the literature as being capable of promoting biological activity. Due to the similarity between 2-AP and other bioactive phenylpropanoids, the present research aims at evaluating the antioxidant, antinociceptive, and anti-inflammatory potential of 2-AP in silico, in vitro, and in vivo. At 30 min prior to the start of in vivo pharmacological testing, administration of 2-AP (25, 50, 75, and 100 mg/kg i.p.), morphine (6 mg/kg i.p.), dexamethasone (2 mg/kg s.c.), or vehicle alone was performed. In the acetic acid-induced abdominal writhing tests, pretreatment with 2-AP significantly reduced the number of abdominal writhes, as well as decreased licking times in the glutamate and formalin tests. Investigation of the mechanism of action using the formalin model led to the conclusion that the opioid system does not participate in its activity. However, the adenosinergic system is involved. In the peritonitis tests, 2-AP inhibited leukocyte migration and reduced releases of proinflammatory mediators TNF-α and IL-1β. In vitro antioxidant assays demonstrated that 2-AP presents significant ability to sequester superoxide radicals. In silico docking studies confirmed interaction between 2-AP and the adenosine A2a receptor through hydrogen bonds with the critical asparagine 253 residues present in the active site. Investigation of 2-AP demonstrated its nociception inhibition and ability to reduce reactive oxygen species. Its interaction with A2a receptors may well be related to proinflammatory cytokines TNF-α and IL-1β reduction activity, corroborating its antinociceptive effect. |
format | Online Article Text |
id | pubmed-6462329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-64623292019-05-02 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms Aragão Neto, Humberto de Carvalho da Fonsêca, Diogo Vilar Braga, Renan Marinho Scotti, Marcus Tullius do Nascimento, Terezinha Weyne Araújo Borges Assis, Davidson Barbosa Rodrigues-Mascarenhas, Sandra Silva, Luiz Henrique Agra Cavalcante Galvão, José Guilherme Ferreira Marques Rocha, Hugo Alexandre Oliveira Vidal, Arthur Antunes Jacome Filho, José Maria Barbosa de Almeida, Reinaldo Nóbrega Oxid Med Cell Longev Research Article 2-Allylphenol (2-AP) is a synthetic phenylpropanoid, structurally related to cardanol, thymol, and ortho-eugenol. Phenylpropanoids are described in the literature as being capable of promoting biological activity. Due to the similarity between 2-AP and other bioactive phenylpropanoids, the present research aims at evaluating the antioxidant, antinociceptive, and anti-inflammatory potential of 2-AP in silico, in vitro, and in vivo. At 30 min prior to the start of in vivo pharmacological testing, administration of 2-AP (25, 50, 75, and 100 mg/kg i.p.), morphine (6 mg/kg i.p.), dexamethasone (2 mg/kg s.c.), or vehicle alone was performed. In the acetic acid-induced abdominal writhing tests, pretreatment with 2-AP significantly reduced the number of abdominal writhes, as well as decreased licking times in the glutamate and formalin tests. Investigation of the mechanism of action using the formalin model led to the conclusion that the opioid system does not participate in its activity. However, the adenosinergic system is involved. In the peritonitis tests, 2-AP inhibited leukocyte migration and reduced releases of proinflammatory mediators TNF-α and IL-1β. In vitro antioxidant assays demonstrated that 2-AP presents significant ability to sequester superoxide radicals. In silico docking studies confirmed interaction between 2-AP and the adenosine A2a receptor through hydrogen bonds with the critical asparagine 253 residues present in the active site. Investigation of 2-AP demonstrated its nociception inhibition and ability to reduce reactive oxygen species. Its interaction with A2a receptors may well be related to proinflammatory cytokines TNF-α and IL-1β reduction activity, corroborating its antinociceptive effect. Hindawi 2019-03-31 /pmc/articles/PMC6462329/ /pubmed/31049124 http://dx.doi.org/10.1155/2019/1346878 Text en Copyright © 2019 Humberto de Carvalho Aragão Neto et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Aragão Neto, Humberto de Carvalho da Fonsêca, Diogo Vilar Braga, Renan Marinho Scotti, Marcus Tullius do Nascimento, Terezinha Weyne Araújo Borges Assis, Davidson Barbosa Rodrigues-Mascarenhas, Sandra Silva, Luiz Henrique Agra Cavalcante Galvão, José Guilherme Ferreira Marques Rocha, Hugo Alexandre Oliveira Vidal, Arthur Antunes Jacome Filho, José Maria Barbosa de Almeida, Reinaldo Nóbrega 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title | 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title_full | 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title_fullStr | 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title_full_unstemmed | 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title_short | 2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms |
title_sort | 2-allylphenol reduces il-1β and tnf-α, promoting antinociception through adenosinergic, anti-inflammatory, and antioxidant mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462329/ https://www.ncbi.nlm.nih.gov/pubmed/31049124 http://dx.doi.org/10.1155/2019/1346878 |
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