Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana

Detalhes bibliográficos
Autor(a) principal: LIMA, Nathalia de Fátima Melo
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFMA
Texto Completo: https://tedebc.ufma.br/jspui/handle/tede/tede/2405
Resumo: Introduction: Persea americana Mill is a plant species traditionally used in traditional Brazilian medicine for the treatment of inflammatory and algic processes. Objectives: To evaluate the anti-inflammatory and antinociceptive effect of the hydroalcoholic extract of the leaves of Persea americana Mill (EHPa) on pain and inflammation models, as well as to investigate the possible mechanisms involved in the action of this species. Materials and Methods: To identify the existing compounds in EHPa, the HPLC was terminated. The activity of EHPa was evaluated using mus musculus mice (males, ± 45 days) in the paw edema test induced by carrageenan and dextran, for anti-inflammatory action; abdominal contortions induced by acetic acid, formalin and glutamate for antinociceptive action. For evaluation of the involvement of opioid receptors and participation of the L-arginine-NO pathway in antinociceptive action, previously treated with naloxone and L-NAME, respectively. For in vitro analysis, the COX- 1 and COX-2 inhibition test was used. Results: The HPLC identified compounds such as β-amirin, caffeic acid, coumaric acid, isoquercitrin, naringerin and canferol. Treatment with EHPa (250 and 500mg / kg) reduced carrageenaninduced paw edema by 40% and 70%, respectively; A similar result was obtained with the 500mg / kg EHPa in the induction of dextran edema (50% reduction), evidencing the anti-inflammatory power of the species. In the in vitro test, the EHPa inhibited the Cycloxigenases, presenting greater selectivity for COX-2, when compared to COX-1. EHPa (50, 250 and 500mg / kg) reduced nociception caused by acetic acid, as well as the second (inflammatory) phase of the formalin test, in the neurogenic phase of the formalin test, EHPa at doses of 250 and 500 mg / kg was able to reduce the reaction time of the animals in 51% and 71.1% respectively . In the glutamate test, EHPa (50, 250 and 500mg / kg) reversed the nociception caused by intraplantar glutamate injection in 61.2%, 71.7% and 86% respectively. Naloxone was not able to reverse the action of EHPa (500mg / kg) in the neurogenic phase of the formalin test. In contrast, naloxone was able to block the antinociceptive effect of EHPa in the inflammatory phase. L-NAME was not able to reverse central antinociceptive action of EHPa; In the inflammatory phase, L-NAME was able to further increase the peripheral antinociceptive action of EHPa in 49.3%. Conclusion: EHPa has significant anti-inflammatory and antinociceptive effects. The anti-inflammatory action of EHPa involves the participation of histamine and / or 5HT, in addition to the inhibition of cycloxigenases, having greater COX-2 selectivity. Opioid receptors are not involved in the central antinociceptive activity of EHPa, but the possible participation of NMDA receptors was evidenced. The peripheral antinociceptive action of EHPa seems to involve opioid receptors and NO modulation.
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spelling CARTÁGENES, Maria do Socorro de Sousa407888653-15http://lattes.cnpq.br/3013333572719007GARCIA, João Batista Santos135570488-02http://lattes.cnpq.br/0424234103760462CARTÁGENES, Maria do Socorro de Sousa407888653-15http://lattes.cnpq.br/3013333572719007GARCIA, João Batista Santos135570488-02http://lattes.cnpq.br/0424234103760462LIMA, Fernando Cesar Vilhena Moreirahttp://lattes.cnpq.br/7926405018339971MONTEIRO, Sally Cristina Moutinhohttp://lattes.cnpq.br/4190147129451754SANTOS, Orlando José doshttp://lattes.cnpq.br/3416873348262526028798273-45http://lattes.cnpq.br/4778313001213808LIMA, Nathalia de Fátima Melo2018-10-16T20:03:19Z2018-06-26LIMA, Nathalia De Fátima Melo. Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana. 2018. 72f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.https://tedebc.ufma.br/jspui/handle/tede/tede/2405Introduction: Persea americana Mill is a plant species traditionally used in traditional Brazilian medicine for the treatment of inflammatory and algic processes. Objectives: To evaluate the anti-inflammatory and antinociceptive effect of the hydroalcoholic extract of the leaves of Persea americana Mill (EHPa) on pain and inflammation models, as well as to investigate the possible mechanisms involved in the action of this species. Materials and Methods: To identify the existing compounds in EHPa, the HPLC was terminated. The activity of EHPa was evaluated using mus musculus mice (males, ± 45 days) in the paw edema test induced by carrageenan and dextran, for anti-inflammatory action; abdominal contortions induced by acetic acid, formalin and glutamate for antinociceptive action. For evaluation of the involvement of opioid receptors and participation of the L-arginine-NO pathway in antinociceptive action, previously treated with naloxone and L-NAME, respectively. For in vitro analysis, the COX- 1 and COX-2 inhibition test was used. Results: The HPLC identified compounds such as β-amirin, caffeic acid, coumaric acid, isoquercitrin, naringerin and canferol. Treatment with EHPa (250 and 500mg / kg) reduced carrageenaninduced paw edema by 40% and 70%, respectively; A similar result was obtained with the 500mg / kg EHPa in the induction of dextran edema (50% reduction), evidencing the anti-inflammatory power of the species. In the in vitro test, the EHPa inhibited the Cycloxigenases, presenting greater selectivity for COX-2, when compared to COX-1. EHPa (50, 250 and 500mg / kg) reduced nociception caused by acetic acid, as well as the second (inflammatory) phase of the formalin test, in the neurogenic phase of the formalin test, EHPa at doses of 250 and 500 mg / kg was able to reduce the reaction time of the animals in 51% and 71.1% respectively . In the glutamate test, EHPa (50, 250 and 500mg / kg) reversed the nociception caused by intraplantar glutamate injection in 61.2%, 71.7% and 86% respectively. Naloxone was not able to reverse the action of EHPa (500mg / kg) in the neurogenic phase of the formalin test. In contrast, naloxone was able to block the antinociceptive effect of EHPa in the inflammatory phase. L-NAME was not able to reverse central antinociceptive action of EHPa; In the inflammatory phase, L-NAME was able to further increase the peripheral antinociceptive action of EHPa in 49.3%. Conclusion: EHPa has significant anti-inflammatory and antinociceptive effects. The anti-inflammatory action of EHPa involves the participation of histamine and / or 5HT, in addition to the inhibition of cycloxigenases, having greater COX-2 selectivity. Opioid receptors are not involved in the central antinociceptive activity of EHPa, but the possible participation of NMDA receptors was evidenced. The peripheral antinociceptive action of EHPa seems to involve opioid receptors and NO modulation.Persea americana Mill é uma espécie vegetal tradicionalmente utilizada na medicina tradicional brasileira no tratamento de processos álgicos e inflamatórios. Objetivos: Avaliar o efeito anti-inflamatório e antinociceptivo do extrato hidroalcoolico das folhas de Persea americana Mill (EHPa) em modelos de dor e inflamação, bem como investigar os possíveis mecanismos envolvidos na ação desta espécie. Materiais e Métodos: Para identificação dos compostos existentes no EHPa ultizou-se a CLAE. A atividade do EHPa foi avaliada utilizando camundongos mus musculus (machos, ±45 dias) no teste de edema de pata induzido por carragenina e dextrana, para ação anti-inflamatoria e; contorções abdominais induzidas por ácido acétco, formalina e glutamato para ação antinociceptiva. Para avaliação do envolvimento de receptors opioides e participação da via L-arginina-NO na ação antinociceptiva, tratou-se previamente com naloxona e L-NAME, respectivamente. Para análise in vitro, utilizou-se o teste de inibição de COX-1 e COX-2 e a docagem molecular para avaliar o composto que melhor interagiu com a COX-2. Resultados: A CLAE identificou compostos como a β-amirina, ácido cafeico, ácido cumárico, isoquercitrina, naringerina e canferol. O tratamento com EHPa 250 e 500mg/kg reduziu o edema de pata induzido por carragenina em 40% e 70%, repectivamente; resultado semelhante foi obtido com o EHPa na dose de 500mg/kg na indução de edema por dextrana (redução de 50%), evidenciando o poder anti-inflamatório da espécie. O EHPa (50, 250 e 500mg/kg) reduziu a nocicepção causada pelo ácido acético, assim como também na segunda fase (inflamatória) do teste de formalina. Na fase neurogênica do teste de formalina, o EHPa nas doses de 250 e 500mg/kg conseguiu reduzir o tempo de reação dos animais em 51% e 71,1%, respectivamente. No teste de glutamato, o EHPa (50, 250 e 500mg/kg) reverteu a nocicepção causada pela injeção intraplantar de glutamato em 61,2%, 71,7% e 86% respectivamente. A naloxona não foi capaz de reverter a ação desempenha pelo EHPa (500mg/kg) na fase neurogênica do teste de formalina. Em contrapartida, a naloxona foi capaz de bloquear o efeito antinociceptivo do EHPa na fase inflamatória. O L-NAME não foi capaz de reverter ação antinociceptiva central do EHPa; Na fase inflamatoria, o LNAME foi capaz de aumentar ainda mais a ação antinociceptiva periférica do EHPa em 49,3%. No teste in vitro, o EHPa inibiu as Cicloxigenases, apresentando maior seletividade para COX-2, quando comparada a COX-1. A β-amirina foi o composto que melhor interagiu com a COX-2. Conclusão: O EHPa tem efeitos antiinflamatórios e antinociceptivos significativos. A ação anti-inflamatória do EHPa envolve a participação de histamina e/ou 5HT, além da inibição das cicloxigenases, tendo maior seletividade por COX-2, causada pelo menos em parte, pela β-amirina. Os receptores opioides não estão envolvidos na atividade antinociceptiva central do EHPa, porém evidenciou-se a possível participação de receptores do tipo NMDA. A ação antinociceptiva periférica do EHPa parece envolver receptores opioides e a modulação de NO.Submitted by Daniella Santos (daniella.santos@ufma.br) on 2018-10-16T20:03:19Z No. of bitstreams: 1 NathaliaLima.pdf: 1182125 bytes, checksum: 128540032514498cce64ad4991f91b09 (MD5)Made available in DSpace on 2018-10-16T20:03:19Z (GMT). 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dc.title.por.fl_str_mv Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
dc.title.alternative.eng.fl_str_mv Mechanism of action of antinociceptive activity and anti-inflammatory drug from Persea americana
title Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
spellingShingle Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
LIMA, Nathalia de Fátima Melo
Persea americana
COX-2
receptor opioide
NO
β-amirina
Persea americana
COX-2
opioid receptor
NO
β-amyrin
Ciências da Saúde
title_short Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
title_full Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
title_fullStr Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
title_full_unstemmed Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
title_sort Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana
author LIMA, Nathalia de Fátima Melo
author_facet LIMA, Nathalia de Fátima Melo
author_role author
dc.contributor.advisor1.fl_str_mv CARTÁGENES, Maria do Socorro de Sousa
dc.contributor.advisor1ID.fl_str_mv 407888653-15
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3013333572719007
dc.contributor.advisor-co1.fl_str_mv GARCIA, João Batista Santos
dc.contributor.advisor-co1ID.fl_str_mv 135570488-02
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/0424234103760462
dc.contributor.referee1.fl_str_mv CARTÁGENES, Maria do Socorro de Sousa
dc.contributor.referee1ID.fl_str_mv 407888653-15
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/3013333572719007
dc.contributor.referee2.fl_str_mv GARCIA, João Batista Santos
dc.contributor.referee2ID.fl_str_mv 135570488-02
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0424234103760462
dc.contributor.referee3.fl_str_mv LIMA, Fernando Cesar Vilhena Moreira
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7926405018339971
dc.contributor.referee4.fl_str_mv MONTEIRO, Sally Cristina Moutinho
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/4190147129451754
dc.contributor.referee5.fl_str_mv SANTOS, Orlando José dos
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/3416873348262526
dc.contributor.authorID.fl_str_mv 028798273-45
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4778313001213808
dc.contributor.author.fl_str_mv LIMA, Nathalia de Fátima Melo
contributor_str_mv CARTÁGENES, Maria do Socorro de Sousa
GARCIA, João Batista Santos
CARTÁGENES, Maria do Socorro de Sousa
GARCIA, João Batista Santos
LIMA, Fernando Cesar Vilhena Moreira
MONTEIRO, Sally Cristina Moutinho
SANTOS, Orlando José dos
dc.subject.por.fl_str_mv Persea americana
COX-2
receptor opioide
NO
β-amirina
topic Persea americana
COX-2
receptor opioide
NO
β-amirina
Persea americana
COX-2
opioid receptor
NO
β-amyrin
Ciências da Saúde
dc.subject.eng.fl_str_mv Persea americana
COX-2
opioid receptor
NO
β-amyrin
dc.subject.cnpq.fl_str_mv Ciências da Saúde
description Introduction: Persea americana Mill is a plant species traditionally used in traditional Brazilian medicine for the treatment of inflammatory and algic processes. Objectives: To evaluate the anti-inflammatory and antinociceptive effect of the hydroalcoholic extract of the leaves of Persea americana Mill (EHPa) on pain and inflammation models, as well as to investigate the possible mechanisms involved in the action of this species. Materials and Methods: To identify the existing compounds in EHPa, the HPLC was terminated. The activity of EHPa was evaluated using mus musculus mice (males, ± 45 days) in the paw edema test induced by carrageenan and dextran, for anti-inflammatory action; abdominal contortions induced by acetic acid, formalin and glutamate for antinociceptive action. For evaluation of the involvement of opioid receptors and participation of the L-arginine-NO pathway in antinociceptive action, previously treated with naloxone and L-NAME, respectively. For in vitro analysis, the COX- 1 and COX-2 inhibition test was used. Results: The HPLC identified compounds such as β-amirin, caffeic acid, coumaric acid, isoquercitrin, naringerin and canferol. Treatment with EHPa (250 and 500mg / kg) reduced carrageenaninduced paw edema by 40% and 70%, respectively; A similar result was obtained with the 500mg / kg EHPa in the induction of dextran edema (50% reduction), evidencing the anti-inflammatory power of the species. In the in vitro test, the EHPa inhibited the Cycloxigenases, presenting greater selectivity for COX-2, when compared to COX-1. EHPa (50, 250 and 500mg / kg) reduced nociception caused by acetic acid, as well as the second (inflammatory) phase of the formalin test, in the neurogenic phase of the formalin test, EHPa at doses of 250 and 500 mg / kg was able to reduce the reaction time of the animals in 51% and 71.1% respectively . In the glutamate test, EHPa (50, 250 and 500mg / kg) reversed the nociception caused by intraplantar glutamate injection in 61.2%, 71.7% and 86% respectively. Naloxone was not able to reverse the action of EHPa (500mg / kg) in the neurogenic phase of the formalin test. In contrast, naloxone was able to block the antinociceptive effect of EHPa in the inflammatory phase. L-NAME was not able to reverse central antinociceptive action of EHPa; In the inflammatory phase, L-NAME was able to further increase the peripheral antinociceptive action of EHPa in 49.3%. Conclusion: EHPa has significant anti-inflammatory and antinociceptive effects. The anti-inflammatory action of EHPa involves the participation of histamine and / or 5HT, in addition to the inhibition of cycloxigenases, having greater COX-2 selectivity. Opioid receptors are not involved in the central antinociceptive activity of EHPa, but the possible participation of NMDA receptors was evidenced. The peripheral antinociceptive action of EHPa seems to involve opioid receptors and NO modulation.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-10-16T20:03:19Z
dc.date.issued.fl_str_mv 2018-06-26
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv LIMA, Nathalia De Fátima Melo. Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana. 2018. 72f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.
dc.identifier.uri.fl_str_mv https://tedebc.ufma.br/jspui/handle/tede/tede/2405
identifier_str_mv LIMA, Nathalia De Fátima Melo. Mecanismo de ação da atividade antinociceptiva e anti-inflamatória da Persea americana. 2018. 72f. Dissertação (Programa de Pós-Graduação em Saúde do Adulto e da Criança/CCBS) - Universidade Federal do Maranhão, São Luís.
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