Potencial efeito anti-hiperalgésico, anti-inflamatório e pró-resolutivo da inalação do óleo essencial Pogostemon Cablin em camundongos: análise da via Anexina a1 / FPR2 / Opioide

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Emer, Aline Armiliato
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.animaeducacao.com.br/handle/ANIMA/3107
Resumo: Introduction: Natural products have been targeted for the development of novel therapeutic strategies for the treatment of inflammatory diseases. In particular the Pogostemon cablin essential oil (PcEO), rich in sesquiterpenes, has traditionally been shown to produce anti-inflammatory effect. However, the mechanism of action involved in the anti-inflammatory effect of inhaled PcEO, has not yet been investigated. Objective: To evaluate the antihyperalgesic, antiinflammatory and pro-resolution effect of PcEO inhalation in preclinical models of inflammation and to analyze the AnxA1/FPR2/opioid pathway. Methods: Initially the phytochemical profile of PcEO was characterized by chromatographic analysis. In the behavioral experiments were used female Swiss mice. The animals underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). The mechanical hyperalgesia was evaluated by the von Frey test and the paw thickness evaluated by the micrometer. The animals were treated with PcEO for up to 5 days. The evaluation of the antihyperalgesic mechanism was performed by analyzing the involvement of formyl-peptide receptor (FPR2) and opioids. Subcutaneous administration (s.c.), i.pl. and intrathecally (i.t.) of the antagonist for the FPR2 receptor or naloxone were performed on the first and fifth day after CFA. Pro- and anti-inflammatory cytokines were analyzed. Animals knockout (AnxA1 -/-) were assessed for mechanical hyperalgesia and paw thickness. In pleural inflammation induced by carrageenan, cytokines were analyzed, total and differential leukocyte count. Anosmia was induced by the intranasal injection of zicam, the animals were evaluated in the olfactory discrimination test, mechanical hyperalgesia, locomotor activity and tail suspension test. Results: The chemical compounds present in the PcEO were identified as patchoulol, α-bulnesene, α-guaiene, α-copaene, β-patchoulene, β-elemene, cycloseichelene, trans-β-caryophyllene, seichhelene, α-patchoulene, guai-4,11-diene and pogostol. The inhalation of PcEO reduced mechanical hyperalgesia, but not edema. It had no effect on pro-and anti-inflammatory cytokine concentrations. FPR2 receptors (systemic and spinal) and opioids (systemic, peripheral and spinal), as well as the participation of AnxA1, participate in the antihyperalgesic effect of the inhaled PcEO. In the pleurisy model, there was reduction of cellular infiltrates and inflammatory cytokines. Olfactory pathway activation is not necessary for the antihyperalgesic effect of PcEO inhalation. Conclusion: The present study showed that inhalation of PcEO was effective in reducing mechanical hyperalgesia in the persistent inflammation model, in which the AnxA1/FPR2/opioid pathway is involved, but did not reduce edema and had no effect on pro-and anti-inflammatory cytokine concentrations. In addition, it has been demonstrated that olfactory pathway activation is not required for the antihyperalgesic effect. In the model of pleurisy, the inhaled PcEO showed an anti-inflammatory effect.