Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/tede/6810 |
Resumo: | The essential oils of herbs have a variety of bioactive compounds, such as monoterpenes. These monoterpenes have several pharmacological activities described as analgesic, anti-inflammatory, antidepressant and anticonvulsant, among others. The (-)- myrtenol is a monoterpene alcohol monocyclic, of pleasant odor, used in the cosmetics industry. However, the absence of research on possible pharmacological activities of this monoterpene has encouraged the present research. This study investigates the effect of (-)- myrtenol, intraperitoneally in adult male Swiss mice under experimental models of pain and inflammation. Initially, the research was initiated with lethal dose 50 (LD50) of monoterpene, in order to establish safe doses for subsequent tests. To investigate the action profile of monoterpene in the central nervous system, a pharmacological screening behavior was carried out, the effect of which in animals treated with (-)- myrtenol was that of analgesia. Then methodologies were conducted to evaluate the antinociceptive activity. The (-)- myrtenol (25, 50 and 100 mg/kg, i.p) increased the latency to the onset of abdominal writhing induced by acetic acid and reduced the number of writhing when compared to the control group. In the formalin test, using the same doses, (-) myrtenol did not alter the duration of paw licking in the neurogenic phase (0-5 min), but it inhibited significantly (p <0,001) the time of paw licking along the inflammatory phase (15-30 min). In the test of nociception induced by glutamate, the three doses of monoterpene reduced time of paw licking. In the hot plate test, which is sensitive and specific to drugs that act through a central mechanism, the (-)- myrtenol did not alter the paw withdrawal latency. With these results, we propose that the antinociceptive action of (-)- myrtenol may be a peripheral and not central mechanism of action. In an attempt to elucidate the mechanism of action involved in the antinociceptive effect of (-)- myrtenol, pharmacological tools were used in the formalin test. The antinociception produced by (-)- myrtenol (100 mg/kg, i.p) was reversed by naloxone (5 mg/kg, s.c) naloxonazine (10 mg/kg, s.c), glibenclamide (10 mg/kg, s.c), L-NOARG (50mg/kg, i.p) and yohimbine (0,15 mg/kg, i.p) only in the second phase of the formalin test. In view of the outstanding action of monoterpene in the second phase of the formalin test, we have investigated its possible anti-inflammatory activity. In this evaluation, treatment with (-)- myrtenol (50 and 100 mg/kg, i.p) was effective in reducing the paw edema induced by carrageenan (500 mg / paw), prostaglandin E2 (5 nmol / paw) and bradykinin (3 nmol / paw) at all times tested. In the model of carrageenan-induced peritonitis (1%), the monoterpene decreased the influx of leukocytes and also the levels of IL-1β and TNF-α in peritoneal fluid. Therefore, this study has demonstrated that (-)- myrtenol has antinociceptive activity with the participation of opioid receptor μ1, K+ATP channels, oxidonitrergic and adrenergic α2. Furthermore, (-)- myrtenol has exhibited anti-inflammatory activity by inhibiting the formation of paw edema and reduced leukocyte influx, possibly by inhibiting the production of pro-inflammatory cytokines IL-1β and TNF-α. |
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Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenolMechanism of action of the antinociceptive and anti-inflammatory (-) myrtenol(-)- MirtenolDorAntinocicepçãoAnti-inflamatórioMonoterpenoMecanismo de ação(-)-MyrtenolPainAntinociceptionAnti-inflammatoryMonoterpeneMechanism of actionCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIAThe essential oils of herbs have a variety of bioactive compounds, such as monoterpenes. These monoterpenes have several pharmacological activities described as analgesic, anti-inflammatory, antidepressant and anticonvulsant, among others. The (-)- myrtenol is a monoterpene alcohol monocyclic, of pleasant odor, used in the cosmetics industry. However, the absence of research on possible pharmacological activities of this monoterpene has encouraged the present research. This study investigates the effect of (-)- myrtenol, intraperitoneally in adult male Swiss mice under experimental models of pain and inflammation. Initially, the research was initiated with lethal dose 50 (LD50) of monoterpene, in order to establish safe doses for subsequent tests. To investigate the action profile of monoterpene in the central nervous system, a pharmacological screening behavior was carried out, the effect of which in animals treated with (-)- myrtenol was that of analgesia. Then methodologies were conducted to evaluate the antinociceptive activity. The (-)- myrtenol (25, 50 and 100 mg/kg, i.p) increased the latency to the onset of abdominal writhing induced by acetic acid and reduced the number of writhing when compared to the control group. In the formalin test, using the same doses, (-) myrtenol did not alter the duration of paw licking in the neurogenic phase (0-5 min), but it inhibited significantly (p <0,001) the time of paw licking along the inflammatory phase (15-30 min). In the test of nociception induced by glutamate, the three doses of monoterpene reduced time of paw licking. In the hot plate test, which is sensitive and specific to drugs that act through a central mechanism, the (-)- myrtenol did not alter the paw withdrawal latency. With these results, we propose that the antinociceptive action of (-)- myrtenol may be a peripheral and not central mechanism of action. In an attempt to elucidate the mechanism of action involved in the antinociceptive effect of (-)- myrtenol, pharmacological tools were used in the formalin test. The antinociception produced by (-)- myrtenol (100 mg/kg, i.p) was reversed by naloxone (5 mg/kg, s.c) naloxonazine (10 mg/kg, s.c), glibenclamide (10 mg/kg, s.c), L-NOARG (50mg/kg, i.p) and yohimbine (0,15 mg/kg, i.p) only in the second phase of the formalin test. In view of the outstanding action of monoterpene in the second phase of the formalin test, we have investigated its possible anti-inflammatory activity. In this evaluation, treatment with (-)- myrtenol (50 and 100 mg/kg, i.p) was effective in reducing the paw edema induced by carrageenan (500 mg / paw), prostaglandin E2 (5 nmol / paw) and bradykinin (3 nmol / paw) at all times tested. In the model of carrageenan-induced peritonitis (1%), the monoterpene decreased the influx of leukocytes and also the levels of IL-1β and TNF-α in peritoneal fluid. Therefore, this study has demonstrated that (-)- myrtenol has antinociceptive activity with the participation of opioid receptor μ1, K+ATP channels, oxidonitrergic and adrenergic α2. Furthermore, (-)- myrtenol has exhibited anti-inflammatory activity by inhibiting the formation of paw edema and reduced leukocyte influx, possibly by inhibiting the production of pro-inflammatory cytokines IL-1β and TNF-α.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOs óleos essenciais obtidos de plantas medicinais possuem uma variedade de compostos bioativos, como os monoterpenos. Estes monoterpenos possuem distintas atividades farmacológicas descritas, como analgésica, anti-inflamatória, antidepressiva e anticonvulsivante dentre outras. O (-)-mirtenol é um monoterpeno, álcool monocíclico, de odor agradável, utilizado na indústria de cosméticos. No entanto, a ausência de pesquisas sobre as possíveis atividades farmacológicas deste monoterpeno incentivou à realização deste trabalho. O presente estudo investigou o efeito do (-)- mirtenol, pela via intraperitoneal, em camundongos suíços machos adultos em modelos experimentais de dor e de inflamação. Inicialmente, foi realizada a pesquisa da dose letal 50 (DL50) do monoterpeno, no intuito de estabelecer doses seguras para os testes subsequentes. Para investigar o perfil de ação do monoterpeno no sistema nervoso central foi realizado a triagem farmacológica comportamental e o principal efeito observado nos animais tratados com (-)- mirtenol foi analgesia. Em seguida, foram realizadas metodologias para avaliar a atividade antinociceptiva. O (-)- mirtenol (25, 50 e 100 mg/kg, i.p.) aumentou a latência para o inicio das contorções abdominais induzidas por ácido acético e reduziu o número de contorções, quando comparado ao grupo controle. No teste da formalina, utilizando as mesmas doses, o (-) - mirtenol não alterou o tempo de lambida da pata na fase neurogênica (0-5 min), mas inibiu significativamente (p<0,001) o tempo de lambida da pata na fase inflamatória (15-30 min). No teste da nocicepção induzida por glutamato, as três doses do monoterpeno reduziram o tempo de lambida da pata. Já no teste da placa quente, que é sensível e específico para drogas que atuam por mecanismo central, o (-)- mirtenol não alterou a latência na retirada da pata. Com estes resultados podemos propor que a ação antinociceptiva do (-)- mirtenol pode ser por mecanismo de ação periférica e não central. Na tentativa de elucidar o mecanismo de ação envolvido no efeito antinociceptivo do (-)- mirtenol foram usadas ferramentas farmacológicas no teste da formalina. A antinocicepção produzida pelo (-)- mirtenol (100 mg/kg i.p.) foi revertida pela naloxona (5 mg/kg s.c.), naloxonazine (10 mg/kg s.c.), glibenclamida (10 mg/kg s.c.), L-NOARG (50mg/kg i.p.) e ioimbina (0,15 mg/kg i.p) somente na segunda fase do teste da formalina. Tendo em vista a destacada ação do monoterpeno na segunda fase do teste da formalina, investigamos sua possível atividade anti-inflamatória. Nessa avaliação, o tratamento com o (-)- mirtenol (50 e 100 mg/kg, i.p.) foi capaz de reduzir o edema de pata induzido por carragenina (500 μg/pata), prostaglandina E2 (5 nmol/pata) e bradicinina (3 nmol/pata) em todos os tempos testados. No modelo da peritonite induzida por carragenina (1%), o monoterpeno diminuiu o influxo de leucócitos e também os níveis das citocinas IL-1β e TNF-α no lavado peritoneal. Portanto, este trabalho demonstrou que o (-)- mirtenol possui atividade antinoceptiva com participação dos sistemas opióidérgico μ1, canais de K+ATP, óxidonitrérgico e α2-adrenérgico. Além disso, possui atividade anti-inflamatória ao inibir a formação do edema de pata e reduzir o influxo de leucócitos possivelmente pela inibição da produção das citocinas pró-inflamatórias IL-1β e TNF-α.Universidade Federal da ParaíbaBRFarmacologiaPrograma de Pós Graduação em Produtos Naturais e Sintéticos BioativosUFPBAlmeida, Reinaldo Nobrega dehttp://lattes.cnpq.br/5034028656386134Salvadori, Mirian Graciela da Silva Stiebbe2015-05-14T12:59:59Z2018-07-21T00:25:06Z2014-09-112018-07-21T00:25:06Z2013-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfSALVADORI, Mirian Graciela da Silva Stiebbe. Mechanism of action of the antinociceptive and anti-inflammatory (-) myrtenol. 2013. 157 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraíba, João Pessoa, 2013.https://repositorio.ufpb.br/jspui/handle/tede/6810porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T01:57:20Zoai:repositorio.ufpb.br:tede/6810Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T01:57:20Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol Mechanism of action of the antinociceptive and anti-inflammatory (-) myrtenol |
title |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
spellingShingle |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol Salvadori, Mirian Graciela da Silva Stiebbe (-)- Mirtenol Dor Antinocicepção Anti-inflamatório Monoterpeno Mecanismo de ação (-)-Myrtenol Pain Antinociception Anti-inflammatory Monoterpene Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
title_full |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
title_fullStr |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
title_full_unstemmed |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
title_sort |
Mecanismo de ação da atividade antinociceptiva e anti-inflamatória do (-) - mirtenol |
author |
Salvadori, Mirian Graciela da Silva Stiebbe |
author_facet |
Salvadori, Mirian Graciela da Silva Stiebbe |
author_role |
author |
dc.contributor.none.fl_str_mv |
Almeida, Reinaldo Nobrega de http://lattes.cnpq.br/5034028656386134 |
dc.contributor.author.fl_str_mv |
Salvadori, Mirian Graciela da Silva Stiebbe |
dc.subject.por.fl_str_mv |
(-)- Mirtenol Dor Antinocicepção Anti-inflamatório Monoterpeno Mecanismo de ação (-)-Myrtenol Pain Antinociception Anti-inflammatory Monoterpene Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
(-)- Mirtenol Dor Antinocicepção Anti-inflamatório Monoterpeno Mecanismo de ação (-)-Myrtenol Pain Antinociception Anti-inflammatory Monoterpene Mechanism of action CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
The essential oils of herbs have a variety of bioactive compounds, such as monoterpenes. These monoterpenes have several pharmacological activities described as analgesic, anti-inflammatory, antidepressant and anticonvulsant, among others. The (-)- myrtenol is a monoterpene alcohol monocyclic, of pleasant odor, used in the cosmetics industry. However, the absence of research on possible pharmacological activities of this monoterpene has encouraged the present research. This study investigates the effect of (-)- myrtenol, intraperitoneally in adult male Swiss mice under experimental models of pain and inflammation. Initially, the research was initiated with lethal dose 50 (LD50) of monoterpene, in order to establish safe doses for subsequent tests. To investigate the action profile of monoterpene in the central nervous system, a pharmacological screening behavior was carried out, the effect of which in animals treated with (-)- myrtenol was that of analgesia. Then methodologies were conducted to evaluate the antinociceptive activity. The (-)- myrtenol (25, 50 and 100 mg/kg, i.p) increased the latency to the onset of abdominal writhing induced by acetic acid and reduced the number of writhing when compared to the control group. In the formalin test, using the same doses, (-) myrtenol did not alter the duration of paw licking in the neurogenic phase (0-5 min), but it inhibited significantly (p <0,001) the time of paw licking along the inflammatory phase (15-30 min). In the test of nociception induced by glutamate, the three doses of monoterpene reduced time of paw licking. In the hot plate test, which is sensitive and specific to drugs that act through a central mechanism, the (-)- myrtenol did not alter the paw withdrawal latency. With these results, we propose that the antinociceptive action of (-)- myrtenol may be a peripheral and not central mechanism of action. In an attempt to elucidate the mechanism of action involved in the antinociceptive effect of (-)- myrtenol, pharmacological tools were used in the formalin test. The antinociception produced by (-)- myrtenol (100 mg/kg, i.p) was reversed by naloxone (5 mg/kg, s.c) naloxonazine (10 mg/kg, s.c), glibenclamide (10 mg/kg, s.c), L-NOARG (50mg/kg, i.p) and yohimbine (0,15 mg/kg, i.p) only in the second phase of the formalin test. In view of the outstanding action of monoterpene in the second phase of the formalin test, we have investigated its possible anti-inflammatory activity. In this evaluation, treatment with (-)- myrtenol (50 and 100 mg/kg, i.p) was effective in reducing the paw edema induced by carrageenan (500 mg / paw), prostaglandin E2 (5 nmol / paw) and bradykinin (3 nmol / paw) at all times tested. In the model of carrageenan-induced peritonitis (1%), the monoterpene decreased the influx of leukocytes and also the levels of IL-1β and TNF-α in peritoneal fluid. Therefore, this study has demonstrated that (-)- myrtenol has antinociceptive activity with the participation of opioid receptor μ1, K+ATP channels, oxidonitrergic and adrenergic α2. Furthermore, (-)- myrtenol has exhibited anti-inflammatory activity by inhibiting the formation of paw edema and reduced leukocyte influx, possibly by inhibiting the production of pro-inflammatory cytokines IL-1β and TNF-α. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-08-01 2014-09-11 2015-05-14T12:59:59Z 2018-07-21T00:25:06Z 2018-07-21T00:25:06Z |
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 |
SALVADORI, Mirian Graciela da Silva Stiebbe. Mechanism of action of the antinociceptive and anti-inflammatory (-) myrtenol. 2013. 157 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraíba, João Pessoa, 2013. https://repositorio.ufpb.br/jspui/handle/tede/6810 |
identifier_str_mv |
SALVADORI, Mirian Graciela da Silva Stiebbe. Mechanism of action of the antinociceptive and anti-inflammatory (-) myrtenol. 2013. 157 f. Tese (Doutorado em Farmacologia) - Universidade Federal da Paraíba, João Pessoa, 2013. |
url |
https://repositorio.ufpb.br/jspui/handle/tede/6810 |
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por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
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UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
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diretoria@ufpb.br|| diretoria@ufpb.br |
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