Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol

Detalhes bibliográficos
Ano de defesa: 2022
Autor(a) principal: Assis, Davidson Barbosa
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: Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Dor
Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/23056
Resumo: 2-Allylphenol (2-AP) is a phenylpropanoid widely marketed in China under the name Yinguo. Extracted from the exosperm of the Ginkgo biloba fruit, 2-AP has previously reported antibacterial, antitumor, antifungal and antinociceptive activities. However, it is necessary to elucidate in more detail the mechanism by which 2-AP promotes its antinociceptive effect, by in silico, in vivo and in vitro methodologies. 2-AP was purchased from SIGMA (St. Louis, MO, USA) and administration was carried out at doses of 50, 75 and 100 mg/kg (i.p.) always thirty minutes before the performance of pharmacological tests. All experimental procedures were previously approved by the CEUA - UFPB's Committee on Ethics in the Use of Animals -, under certificate no. 4443051018. The experiments started with the investigation of the antinociceptive mechanism of 2-AP. To study the participation of the nitroxidergic, GABAergic and dopaminergic systems, respectively, L-NNA, flumazenil and sulpiride were administered fifteen minutes before the treatment with 2-AP in the test of abdominal writhing induced by acetic acid. In order to increase the evidence of the action of 2-AP in the adenosinergic pathway, previously reported, a study of molecular docking was carried out. The carrageenan-induced peritonitis test was used to assess the anti-inflammatory effect of 2-AP by evaluating cell migration and levels of pro-inflammatory cytokines TNF-α and IL-1β in peritoneal fluid. Finally, the antioxidant activity of 2-AP was determined by tests of total antioxidant capacity, DPPH scavenging activity, hydroxyl radical scavenging activity test, superoxide scavenging activity test. Treatment with LNNA, flumazenil and sulpiride did not reverse the antinociceptive effect of 2-AP, ruling out the participation of the nitroxidergic, GABAergic and dopaminergic systems in the antinociceptive effect. Docking studies confirmed an affinity between 2-AP and the A2a receptor, this interaction may be related to the reduction in the production of pro-inflammatory cytokines. In anti-inflammatory tests, 2-AP inhibited leukocyte migration via reduced levels of TNF-α and IL-1β in the peritonitis test. It presented a high total antioxidant capacity, this activity being provided through the scavenging of superoxide radicals, demonstrating that its antioxidant activity may also be helping in the anti-inflammatory and antinociceptive effect. In view of the results, the clinical potential of 2-AP for the treatment of pain and inflammation becomes evident.
id UFPB_e6eb4fad5617dcbf3f01793e0040e558
oai_identifier_str oai:repositorio.ufpb.br:123456789/23056
network_acronym_str UFPB
network_name_str Biblioteca Digital de Teses e Dissertações da UFPB
repository_id_str
spelling Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol2-alilfenolFenilpropanoideDorInflamaçãoAnti-oxidante2-allylphenolPhenylpropanoidPainInflammationAntioxidantCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA2-Allylphenol (2-AP) is a phenylpropanoid widely marketed in China under the name Yinguo. Extracted from the exosperm of the Ginkgo biloba fruit, 2-AP has previously reported antibacterial, antitumor, antifungal and antinociceptive activities. However, it is necessary to elucidate in more detail the mechanism by which 2-AP promotes its antinociceptive effect, by in silico, in vivo and in vitro methodologies. 2-AP was purchased from SIGMA (St. Louis, MO, USA) and administration was carried out at doses of 50, 75 and 100 mg/kg (i.p.) always thirty minutes before the performance of pharmacological tests. All experimental procedures were previously approved by the CEUA - UFPB's Committee on Ethics in the Use of Animals -, under certificate no. 4443051018. The experiments started with the investigation of the antinociceptive mechanism of 2-AP. To study the participation of the nitroxidergic, GABAergic and dopaminergic systems, respectively, L-NNA, flumazenil and sulpiride were administered fifteen minutes before the treatment with 2-AP in the test of abdominal writhing induced by acetic acid. In order to increase the evidence of the action of 2-AP in the adenosinergic pathway, previously reported, a study of molecular docking was carried out. The carrageenan-induced peritonitis test was used to assess the anti-inflammatory effect of 2-AP by evaluating cell migration and levels of pro-inflammatory cytokines TNF-α and IL-1β in peritoneal fluid. Finally, the antioxidant activity of 2-AP was determined by tests of total antioxidant capacity, DPPH scavenging activity, hydroxyl radical scavenging activity test, superoxide scavenging activity test. Treatment with LNNA, flumazenil and sulpiride did not reverse the antinociceptive effect of 2-AP, ruling out the participation of the nitroxidergic, GABAergic and dopaminergic systems in the antinociceptive effect. Docking studies confirmed an affinity between 2-AP and the A2a receptor, this interaction may be related to the reduction in the production of pro-inflammatory cytokines. In anti-inflammatory tests, 2-AP inhibited leukocyte migration via reduced levels of TNF-α and IL-1β in the peritonitis test. It presented a high total antioxidant capacity, this activity being provided through the scavenging of superoxide radicals, demonstrating that its antioxidant activity may also be helping in the anti-inflammatory and antinociceptive effect. In view of the results, the clinical potential of 2-AP for the treatment of pain and inflammation becomes evident.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO 2-alilfenol (2-AF) é um fenilpropanoide amplamente comercializado na China sob o nome de Yinguo. Extraído do exosperma da fruta Ginkgo biloba, o 2-AF apresenta atividade antibacteriana, antitumoral, antifúngica e antinociceptiva já relatadas. Entretanto é necessário elucidar com mais detalhes o mecanismo pelo qual o 2-AF promove seu efeito antinociceptivo por metodologias in silico, in vivo e in vitro. O 2-AF foi adquirido da SIGMA (St. Louis, MO, EUA) e sua administração foi realizada nas doses de 50, 75 e 100 mg/kg (i.p.) sempre trinta minutos antes da realização dos testes farmacológicos. Todos os procedimentos experimentais foram previamente aprovados pelo CEUA - Comissão de Ética no Uso de Animais da UFPB -, sob a certidão de no 4443051018. Os experimentos iniciaram com a investigação do mecanismo antinociceptivo do 2-AF. Para estudar a participação dos sistemas nitroxidérgico, GABAérgico e dopaminérgico administrou-se respectivamente LNNA, flumazenil e sulpirida quinze minutos antes do tratamento com o 2-AF no teste das contorções abdominais induzidas pelo ácido acético. No intuito de aumentar as evidências da atuação do 2-AF na via adenosinérgica, anteriormente relatada, foi realizado um estudo de docking molecular. O teste da peritonite induzida por carragenina foi utilizado para avaliar o efeito antiinflamatório do 2-AF através da avaliação da migração celular e dos níveis das citocinas pró-inflamatórias TNF-α e IL-1β no líquido peritoneal. Por fim, a atividade antioxidante do 2-alilfenol foi determinada pelos testes da capacidade antioxidante total, atividade sequestradora de DPPH, teste da atividade sequestradora do radical hidroxila, teste da atividade sequestradora de superóxido. O tratamento com o L-NNA, flumazenil e sulpirida não reverteram o efeito antinociceptivo do 2-AF, descartando a participação dos sistemas nitroxidérgico, GABAérgico e dopaminérgico no efeito antinociceptivo. Os estudos de docking confirmaram afinidade entre o 2-AF e o receptor A2a, essa interação pode estar relacionada à redução da produção de citocinas próinflamatórias. Nos testes anti-inflamatórios, o 2-AF inibiu a migração de leucócitos via redução dos níveis de TNF-α e IL-1β no teste da peritonite. Apresentou uma alta capacidade antioxidante total sendo esta atividade proporcionada através do sequestro de radicais superóxido, demonstrando que sua atividade antioxidante também pode estar auxiliando no efeito antiinflamatório e antinociceptivo. Diante dos resultados, torna-se evidente o potencial clínico do 2-AF para o tratamento da dor e inflamação.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em MedicamentosUFPBAlmeida, Reinaldo Nóbrega dehttp://lattes.cnpq.br/5034028656386134Assis, Davidson Barbosa2022-06-08T18:25:35Z2022-03-092022-06-08T18:25:35Z2022-02-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/23056porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-08-09T14:04:36Zoai:repositorio.ufpb.br:123456789/23056Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2022-08-09T14:04:36Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
title Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
spellingShingle Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
Assis, Davidson Barbosa
2-alilfenol
Fenilpropanoide
Dor
Inflamação
Anti-oxidante
2-allylphenol
Phenylpropanoid
Pain
Inflammation
Antioxidant
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
title_full Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
title_fullStr Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
title_full_unstemmed Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
title_sort Avaliação da atividade antioxidante e dos mecanismos envolvidos no efeito antinociceptivo e anti-inflamatório do 2-alilfenol
author Assis, Davidson Barbosa
author_facet Assis, Davidson Barbosa
author_role author
dc.contributor.none.fl_str_mv Almeida, Reinaldo Nóbrega de
http://lattes.cnpq.br/5034028656386134
dc.contributor.author.fl_str_mv Assis, Davidson Barbosa
dc.subject.por.fl_str_mv 2-alilfenol
Fenilpropanoide
Dor
Inflamação
Anti-oxidante
2-allylphenol
Phenylpropanoid
Pain
Inflammation
Antioxidant
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic 2-alilfenol
Fenilpropanoide
Dor
Inflamação
Anti-oxidante
2-allylphenol
Phenylpropanoid
Pain
Inflammation
Antioxidant
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description 2-Allylphenol (2-AP) is a phenylpropanoid widely marketed in China under the name Yinguo. Extracted from the exosperm of the Ginkgo biloba fruit, 2-AP has previously reported antibacterial, antitumor, antifungal and antinociceptive activities. However, it is necessary to elucidate in more detail the mechanism by which 2-AP promotes its antinociceptive effect, by in silico, in vivo and in vitro methodologies. 2-AP was purchased from SIGMA (St. Louis, MO, USA) and administration was carried out at doses of 50, 75 and 100 mg/kg (i.p.) always thirty minutes before the performance of pharmacological tests. All experimental procedures were previously approved by the CEUA - UFPB's Committee on Ethics in the Use of Animals -, under certificate no. 4443051018. The experiments started with the investigation of the antinociceptive mechanism of 2-AP. To study the participation of the nitroxidergic, GABAergic and dopaminergic systems, respectively, L-NNA, flumazenil and sulpiride were administered fifteen minutes before the treatment with 2-AP in the test of abdominal writhing induced by acetic acid. In order to increase the evidence of the action of 2-AP in the adenosinergic pathway, previously reported, a study of molecular docking was carried out. The carrageenan-induced peritonitis test was used to assess the anti-inflammatory effect of 2-AP by evaluating cell migration and levels of pro-inflammatory cytokines TNF-α and IL-1β in peritoneal fluid. Finally, the antioxidant activity of 2-AP was determined by tests of total antioxidant capacity, DPPH scavenging activity, hydroxyl radical scavenging activity test, superoxide scavenging activity test. Treatment with LNNA, flumazenil and sulpiride did not reverse the antinociceptive effect of 2-AP, ruling out the participation of the nitroxidergic, GABAergic and dopaminergic systems in the antinociceptive effect. Docking studies confirmed an affinity between 2-AP and the A2a receptor, this interaction may be related to the reduction in the production of pro-inflammatory cytokines. In anti-inflammatory tests, 2-AP inhibited leukocyte migration via reduced levels of TNF-α and IL-1β in the peritonitis test. It presented a high total antioxidant capacity, this activity being provided through the scavenging of superoxide radicals, demonstrating that its antioxidant activity may also be helping in the anti-inflammatory and antinociceptive effect. In view of the results, the clinical potential of 2-AP for the treatment of pain and inflammation becomes evident.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-08T18:25:35Z
2022-03-09
2022-06-08T18:25:35Z
2022-02-04
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/23056
url https://repositorio.ufpb.br/jspui/handle/123456789/23056
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Desenvolvimento e Inovação Tecnológica em Medicamentos
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
_version_ 1801843204568383488