Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil

Detalhes bibliográficos
Autor(a) principal: Assis, Valeria Lopes de
Data de Publicação: 2016
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/123456789/14627
Resumo: Dioclea grandiflora is a Leguminosae family plant, exclusive of the Brazilian Caatinga. Studies have shown various pharmacological properties of extracts or components of the plant, such as antioxidant properties and beneficial effects on the cardiovascular system. However, there are no reports on its activity in erectile function.Thus, this study aimed to characterize the lyophilized of the hydro-alcoholic extract of the bark of D. grandiflora root (LEHDg) and to assess its effect on erectile function of normoglycemic and diabetic rats. To this end, in vivo and in vitro experimental assays were used. LEHDg showed great concentration of phenolic compounds by Folin-Ciocalteu methods and high-performance liquid chromatography (HPLC). Also, this lyophilized demonstrated potent anti-free radical activity against DPPH● radical. In rats corpus cavernosum preparations (CC) pre-contracted by phenylephrine, LEHDg induced concentration dependent relaxation. However, this response was significantly reduced in the presence of L-N-nitro-arginine methyl ester (L-NAME) NOS inhibitor; 2-(4-phenyl)-4,4,5,5-tetrametilimidazolina-1-oxy-3-oxide potassium salt (PTIO), the NO radical scavenger and 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one (ODQ) cyclase inhibitor of soluble guanylyl (CGs), suggesting the involvement of via NOS/NO/CGs in its relaxing effect. The antioxidant activity of LEHDg was evaluated in CC cuts treated by dihidroetid probe (DHE). This lyophilized has reduced the basal fluorescence levels of this probe when compared to the control and the positive control (apocynin), proving antioxidant action. Given these results, we investigated the action of LEHDg on erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. The rats were divided into 5 groups: control group (non-diabetic), STZ group and three STZ groups treated with LEHDg (25 or 37.5 mg/kg) or sildenafil (1.5 mg/kg), which were treated with 28 days. In diabetic rats, body weight decreased and glucose levels increased, when compared to the control group. Treatment with LEHDg or sildenafil did not affect these parameters. Erectile function was assessed by the ratio intracavernous pressure/mean arterial pressure (ICP/MAP). The ICP/MAP in diabetic groups was significantly reduced when compared to the control group. Treatment with sildenafil or LEHDg promoted improvement of this parameter, suggesting a reduction of ED by these treatments. In CC preparations, the maximum contractile response to phenylephrine was significantly increased in diabetic rats compared to controls. Treatments with LEHDg or sildenafil reduced this hypercontractility. Likewise, a significant increase in contractile response induced by electrical field stimulation in CC of diabetic animals, however, only treatment with LEHDg 37.5 mg/kg reduced this effect. The relaxing response induced by acetylcholine was significantly reduced in CC of diabetic animals when compared to the control group. This effect was reversed by treatment with LEHDg or sildenafil. In CC cuts, treatment with sildenafil or LEHDg significantly reduced basal fluorescence of DHE probe when compared to diabetic animals. These results demonstrate that LEHDg is rich in phenolic compounds with potent antioxidant activity that promotes relaxation in CC via NOS/NO/CGs. In animals with diabetes induced ED, LEHDg promotes improvement in erectile function, as well as improved endothelial function, decreased hypercontractility and reducing oxidative stress in the corpus cavernosum.
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spelling Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétilDioclea spp.Corpo cavernosoDiabetesAtividade antioxidanteFunção erétilCorpus cavernosumDiabetesAntioxidant activityErectile functionCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIADioclea grandiflora is a Leguminosae family plant, exclusive of the Brazilian Caatinga. Studies have shown various pharmacological properties of extracts or components of the plant, such as antioxidant properties and beneficial effects on the cardiovascular system. However, there are no reports on its activity in erectile function.Thus, this study aimed to characterize the lyophilized of the hydro-alcoholic extract of the bark of D. grandiflora root (LEHDg) and to assess its effect on erectile function of normoglycemic and diabetic rats. To this end, in vivo and in vitro experimental assays were used. LEHDg showed great concentration of phenolic compounds by Folin-Ciocalteu methods and high-performance liquid chromatography (HPLC). Also, this lyophilized demonstrated potent anti-free radical activity against DPPH● radical. In rats corpus cavernosum preparations (CC) pre-contracted by phenylephrine, LEHDg induced concentration dependent relaxation. However, this response was significantly reduced in the presence of L-N-nitro-arginine methyl ester (L-NAME) NOS inhibitor; 2-(4-phenyl)-4,4,5,5-tetrametilimidazolina-1-oxy-3-oxide potassium salt (PTIO), the NO radical scavenger and 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one (ODQ) cyclase inhibitor of soluble guanylyl (CGs), suggesting the involvement of via NOS/NO/CGs in its relaxing effect. The antioxidant activity of LEHDg was evaluated in CC cuts treated by dihidroetid probe (DHE). This lyophilized has reduced the basal fluorescence levels of this probe when compared to the control and the positive control (apocynin), proving antioxidant action. Given these results, we investigated the action of LEHDg on erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. The rats were divided into 5 groups: control group (non-diabetic), STZ group and three STZ groups treated with LEHDg (25 or 37.5 mg/kg) or sildenafil (1.5 mg/kg), which were treated with 28 days. In diabetic rats, body weight decreased and glucose levels increased, when compared to the control group. Treatment with LEHDg or sildenafil did not affect these parameters. Erectile function was assessed by the ratio intracavernous pressure/mean arterial pressure (ICP/MAP). The ICP/MAP in diabetic groups was significantly reduced when compared to the control group. Treatment with sildenafil or LEHDg promoted improvement of this parameter, suggesting a reduction of ED by these treatments. In CC preparations, the maximum contractile response to phenylephrine was significantly increased in diabetic rats compared to controls. Treatments with LEHDg or sildenafil reduced this hypercontractility. Likewise, a significant increase in contractile response induced by electrical field stimulation in CC of diabetic animals, however, only treatment with LEHDg 37.5 mg/kg reduced this effect. The relaxing response induced by acetylcholine was significantly reduced in CC of diabetic animals when compared to the control group. This effect was reversed by treatment with LEHDg or sildenafil. In CC cuts, treatment with sildenafil or LEHDg significantly reduced basal fluorescence of DHE probe when compared to diabetic animals. These results demonstrate that LEHDg is rich in phenolic compounds with potent antioxidant activity that promotes relaxation in CC via NOS/NO/CGs. In animals with diabetes induced ED, LEHDg promotes improvement in erectile function, as well as improved endothelial function, decreased hypercontractility and reducing oxidative stress in the corpus cavernosum.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESDioclea grandiflora é uma planta da família Leguminosae, exclusiva da caatinga brasileira. Estudos demonstraram diversas propriedades farmacológicas de extratos ou componentes desta planta, como propriedades antioxidantes e efeitos benéficos no sistema cardiovascular. Entretanto, não há relatos sobre sua atividade na função erétil. Desta forma, este estudo objetivou caracterizar o liofilizado do extrato hidroalcoólico da casca da raiz de D. grandiflora (LEHDg), bem como avaliar seu efeito sobre a função erétil de ratos normoglicêmicos e diabéticos. Para isto, foram utilizados ensaios experimentais in vitro e in vivo. LEHDg apresentou grande concentração de compostos fenólicos pelos métodos FolinCiocalteu e cromatografia líquida de alta eficiência (HPLC). Além disso, este liofilizado demonstrou potente atividade anti-radicalar frente ao radical DPPH●. Em preparações de corpo cavernoso (CC) de ratos pré-contraídos por fenilefrina, LEHDg induziu relaxamento dependente de concentração. Entretanto, esta resposta foi significativamente reduzida na presença de L-N-nitro-arginina-metil-éster (L-NAME), inibidor da NOS; 2-(4-fenil)-4,4,5,5tetrametilimidazolina-1-oxi-3-óxido sal de potássio (PTIO), sequestrador do NO radicalar e 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-ona (ODQ), inibidor da ciclase de guanilil solúvel (CGs), sugerindo a participação da via NOS/NO/CGs em seu efeito relaxante. A ação antioxidante do LEHDg foi avaliada em cortes de CC tratados pela sonda dihidroetídeo (DHE). Este liofilizado reduziu os níveis de fluorescência basal desta sonda, quando comparada ao controle e ao controle positivo (apocinina), comprovando ação antioxidante. Diante destes resultados, investigou-se a ação do LEHDg sobre a disfunção erétil (DE) de animais com diabetes induzido por estreptozotocina (STZ). Os ratos foram divididos em 5 grupos: grupo controle (não diabéticos), grupo STZ, três grupos STZ tratados com LEHDg (25 ou 37,5mg/kg) ou com sildenafila (1,5mg/kg), os quais foram tratados por 28 dias. Nos ratos diabéticos, o peso corporal reduziu e os níveis glicêmicos aumentaram, quando comparados ao grupo controle. O tratamento com LEHDg ou sildenafila não afetou estes parâmetros. A função erétil foi avaliada pela relação pressão intracavernosa/pressão arterial média (ICP/MAP). A ICP/MAP nos grupos diabéticos foi significantemente reduzida quando comparada ao grupo controle. Os tratamentos com LEHDg ou sildenafila promoveram melhora deste parâmetro, sugerindo redução da DE por estes tratamentos. Em preparações de CC, a resposta contrátil máxima com fenilefrina foi significantemente aumentada em ratos diabéticos, comparada ao grupo controle. Os tratamentos com LEHDg ou sildenafila reduziram esta hipercontratilidade. Da mesma forma, houve aumento significativo da resposta contrátil induzida pela estimulação por campo elétrico em CC de animais diabéticos, entretanto, apenas o tratamento com LEHDg 37,5mg/kg reduziu este efeito. A resposta relaxante induzida pela acetilcolina foi reduzida significativamente em CC de animais diabéticos quando comparados ao grupo controle. Este efeito foi revertido pelos tratamentos com LEHDg ou sildenafila. Em cortes de CC, o tratamento com LEHDg ou sildenafila reduziu significativamente a fluorescência basal da sonda DHE, quando comparados aos animais diabéticos. Estes resultados demonstram que LEHDg é rico em compostos fenólicos, com potente atividade antioxidante, que promove relaxamento em CC pela via NOS/NO/CGs. Em animais com DE induzida pelo diabetes, LEHDg promove melhora da função erétil, como também melhora da função endotelial, diminuição da hipercontratilidade e redução do estresse oxidativo nos corpos cavernosos.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBMedeiros, Isac Almeida dehttp://lattes.cnpq.br/3412816427200150Assis, Valeria Lopes de2019-06-06T17:29:18Z2019-06-062019-06-06T17:29:18Z2016-02-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/14627porAttribution-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:UFPB2019-06-06T17:29:18Zoai:repositorio.ufpb.br:123456789/14627Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2019-06-06T17:29:18Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
title Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
spellingShingle Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
Assis, Valeria Lopes de
Dioclea spp.
Corpo cavernoso
Diabetes
Atividade antioxidante
Função erétil
Corpus cavernosum
Diabetes
Antioxidant activity
Erectile function
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
title_full Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
title_fullStr Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
title_full_unstemmed Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
title_sort Efeitos do liofilizado do extrato hidroalcoólico da casca da raiz de Dioclea grandiflora Martius ex Bentham em ratos diabéticos com disfunção erétil
author Assis, Valeria Lopes de
author_facet Assis, Valeria Lopes de
author_role author
dc.contributor.none.fl_str_mv Medeiros, Isac Almeida de
http://lattes.cnpq.br/3412816427200150
dc.contributor.author.fl_str_mv Assis, Valeria Lopes de
dc.subject.por.fl_str_mv Dioclea spp.
Corpo cavernoso
Diabetes
Atividade antioxidante
Função erétil
Corpus cavernosum
Diabetes
Antioxidant activity
Erectile function
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Dioclea spp.
Corpo cavernoso
Diabetes
Atividade antioxidante
Função erétil
Corpus cavernosum
Diabetes
Antioxidant activity
Erectile function
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Dioclea grandiflora is a Leguminosae family plant, exclusive of the Brazilian Caatinga. Studies have shown various pharmacological properties of extracts or components of the plant, such as antioxidant properties and beneficial effects on the cardiovascular system. However, there are no reports on its activity in erectile function.Thus, this study aimed to characterize the lyophilized of the hydro-alcoholic extract of the bark of D. grandiflora root (LEHDg) and to assess its effect on erectile function of normoglycemic and diabetic rats. To this end, in vivo and in vitro experimental assays were used. LEHDg showed great concentration of phenolic compounds by Folin-Ciocalteu methods and high-performance liquid chromatography (HPLC). Also, this lyophilized demonstrated potent anti-free radical activity against DPPH● radical. In rats corpus cavernosum preparations (CC) pre-contracted by phenylephrine, LEHDg induced concentration dependent relaxation. However, this response was significantly reduced in the presence of L-N-nitro-arginine methyl ester (L-NAME) NOS inhibitor; 2-(4-phenyl)-4,4,5,5-tetrametilimidazolina-1-oxy-3-oxide potassium salt (PTIO), the NO radical scavenger and 1H-[1,2,4] oxadiazole [4,3-a] quinoxalin-1-one (ODQ) cyclase inhibitor of soluble guanylyl (CGs), suggesting the involvement of via NOS/NO/CGs in its relaxing effect. The antioxidant activity of LEHDg was evaluated in CC cuts treated by dihidroetid probe (DHE). This lyophilized has reduced the basal fluorescence levels of this probe when compared to the control and the positive control (apocynin), proving antioxidant action. Given these results, we investigated the action of LEHDg on erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. The rats were divided into 5 groups: control group (non-diabetic), STZ group and three STZ groups treated with LEHDg (25 or 37.5 mg/kg) or sildenafil (1.5 mg/kg), which were treated with 28 days. In diabetic rats, body weight decreased and glucose levels increased, when compared to the control group. Treatment with LEHDg or sildenafil did not affect these parameters. Erectile function was assessed by the ratio intracavernous pressure/mean arterial pressure (ICP/MAP). The ICP/MAP in diabetic groups was significantly reduced when compared to the control group. Treatment with sildenafil or LEHDg promoted improvement of this parameter, suggesting a reduction of ED by these treatments. In CC preparations, the maximum contractile response to phenylephrine was significantly increased in diabetic rats compared to controls. Treatments with LEHDg or sildenafil reduced this hypercontractility. Likewise, a significant increase in contractile response induced by electrical field stimulation in CC of diabetic animals, however, only treatment with LEHDg 37.5 mg/kg reduced this effect. The relaxing response induced by acetylcholine was significantly reduced in CC of diabetic animals when compared to the control group. This effect was reversed by treatment with LEHDg or sildenafil. In CC cuts, treatment with sildenafil or LEHDg significantly reduced basal fluorescence of DHE probe when compared to diabetic animals. These results demonstrate that LEHDg is rich in phenolic compounds with potent antioxidant activity that promotes relaxation in CC via NOS/NO/CGs. In animals with diabetes induced ED, LEHDg promotes improvement in erectile function, as well as improved endothelial function, decreased hypercontractility and reducing oxidative stress in the corpus cavernosum.
publishDate 2016
dc.date.none.fl_str_mv 2016-02-29
2019-06-06T17:29:18Z
2019-06-06
2019-06-06T17:29:18Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
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dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/14627
url https://repositorio.ufpb.br/jspui/handle/123456789/14627
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 Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
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
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