2-Allylphenol Reduces IL-1β and TNF-α, Promoting Antinociception through Adenosinergic, Anti-Inflammatory, and Antioxidant Mechanisms. (31st March 2019)

• Record Type: Journal Article
• Authors: 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
• Other Names: Nieman David Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2019(2019)
• Publication Date: 2019-03-31
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2019/1346878
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : 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-1 β . 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-1 β reduction activity, corroborating its antinociceptive effect.