Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro

Detalhes bibliográficos
Autor(a) principal: Pellenz, Neida Luiza Kaspary
Data de Publicação: 2019
Tipo de documento: Tese
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/20254
Resumo: Introduction: The skin is the largest organ of the human body and has the functions of coat, delimitate, protec and interact with the external environment. Skin lesions affect the general population, regardless of gender, age or ethnicity, and because of the high rate of people with changes in skin integrity, it is a serious public health problem. The healing of lesions is considered a process of restoration of the homeostasis of the skin, dynamic and highly coordinated, and in recent years there has been a resumption to the valorization of therapeutic practices with the use of herbal medicines in the treatment of various morbidities, including cicatrization of cutaneous lesions. Many plants have already shown promise, especially barbatimão (Stryphnodendron adstringens), several in vitro and in vivo studies have already been performed demonstrating the healing and anti-inflammatory action, however the related mechanisms have not yet been clarified. Objective: To analyze in vitro the causal mechanisms associated with the healing effect of barbatimão (Stryphnodendron adstringens), as well as to carry out literature review and analyze a series of related cases. Methods: Initially, an integrated analysis of the literature related to the healing properties of barbatimão was performed, considering the data available in the main scientific platforms as well as the analysis of a series of cases. The barbatimão shells were obtained, and the hydroalcoholic extract was prepared and characterized chemically via High Performance Liquid Chromatography (HPLC). The extract was tested in vitro in two commercial keratinocyte (HaCaT) and fibroblast (HFF-1) cell lines, grown in an appropriate environment, the pharmacological curves were performed, and once the concentrations of use were determined, analyzes were performed related to cytotoxicity and genotoxicity. In a third phase, the HFF-1 cells, integrals and in vitro lesion model, treated with barbatimão at concentrations of 0.49mg / mL and 0.99mg / mL for 24 or 72 hours, were evaluated: (1) oxidative metabolism (oxidation of DNA, lipoperoxidation, carbonylation of proteins, levels of antioxidant enzymes); (2) proinflammatory cytokines (TNF-α, interleukin 6); (3) apoptotic markers = Caspases (CASPs) 3 and 8 and growth factors (KGF and FGF-1). Results: 42 publications on barbatimão were included in the review, most published in English. From these studies a description of several biological and clinical actions of barbatimão was identified, such as anti - inflammatory, anti - oxidant, antiulcerogenic and antimicrobial effects, antiparasitics, and its curative properties. We report a series of cases of patients submitted to barbatimão for healing of injuries caused by intense involuntary physical trauma (external accidents) or surgery. Considering all cases, the complete duration of healing occurred for 3.6 ± 0.8 months. In relation to study 2, the results demonstrate that the main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin and epigallocatechin-3-gallate (EGCG). The barbatimão was able to decrease the cellular mortality in comparison with the control group, and still presented genoprotective effect to the DNA. In the third study, the treatment with 0.49 mg / mL and 0.99 mg / mL presented a reducing effect on the oxidative, inflammatory and apoptotic markers, concomitantly the barbatimão was able to raise the levels of antioxidants and growth factors. Conclusion: In view of the literature review, the case series, and our in vitro studies, our initial results, which need to be complemented by further studies, give strong indications of the antioxidant, genoprotective, anti-inflammatory, anti -apoptotic, and pro-growth factors of barbatimão, which could explain the efficacy of this herbal medicine in the healing of lesions.
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spelling 2021-01-15T12:09:56Z2021-01-15T12:09:56Z2019-03-11http://repositorio.ufsm.br/handle/1/20254Introduction: The skin is the largest organ of the human body and has the functions of coat, delimitate, protec and interact with the external environment. Skin lesions affect the general population, regardless of gender, age or ethnicity, and because of the high rate of people with changes in skin integrity, it is a serious public health problem. The healing of lesions is considered a process of restoration of the homeostasis of the skin, dynamic and highly coordinated, and in recent years there has been a resumption to the valorization of therapeutic practices with the use of herbal medicines in the treatment of various morbidities, including cicatrization of cutaneous lesions. Many plants have already shown promise, especially barbatimão (Stryphnodendron adstringens), several in vitro and in vivo studies have already been performed demonstrating the healing and anti-inflammatory action, however the related mechanisms have not yet been clarified. Objective: To analyze in vitro the causal mechanisms associated with the healing effect of barbatimão (Stryphnodendron adstringens), as well as to carry out literature review and analyze a series of related cases. Methods: Initially, an integrated analysis of the literature related to the healing properties of barbatimão was performed, considering the data available in the main scientific platforms as well as the analysis of a series of cases. The barbatimão shells were obtained, and the hydroalcoholic extract was prepared and characterized chemically via High Performance Liquid Chromatography (HPLC). The extract was tested in vitro in two commercial keratinocyte (HaCaT) and fibroblast (HFF-1) cell lines, grown in an appropriate environment, the pharmacological curves were performed, and once the concentrations of use were determined, analyzes were performed related to cytotoxicity and genotoxicity. In a third phase, the HFF-1 cells, integrals and in vitro lesion model, treated with barbatimão at concentrations of 0.49mg / mL and 0.99mg / mL for 24 or 72 hours, were evaluated: (1) oxidative metabolism (oxidation of DNA, lipoperoxidation, carbonylation of proteins, levels of antioxidant enzymes); (2) proinflammatory cytokines (TNF-α, interleukin 6); (3) apoptotic markers = Caspases (CASPs) 3 and 8 and growth factors (KGF and FGF-1). Results: 42 publications on barbatimão were included in the review, most published in English. From these studies a description of several biological and clinical actions of barbatimão was identified, such as anti - inflammatory, anti - oxidant, antiulcerogenic and antimicrobial effects, antiparasitics, and its curative properties. We report a series of cases of patients submitted to barbatimão for healing of injuries caused by intense involuntary physical trauma (external accidents) or surgery. Considering all cases, the complete duration of healing occurred for 3.6 ± 0.8 months. In relation to study 2, the results demonstrate that the main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin and epigallocatechin-3-gallate (EGCG). The barbatimão was able to decrease the cellular mortality in comparison with the control group, and still presented genoprotective effect to the DNA. In the third study, the treatment with 0.49 mg / mL and 0.99 mg / mL presented a reducing effect on the oxidative, inflammatory and apoptotic markers, concomitantly the barbatimão was able to raise the levels of antioxidants and growth factors. Conclusion: In view of the literature review, the case series, and our in vitro studies, our initial results, which need to be complemented by further studies, give strong indications of the antioxidant, genoprotective, anti-inflammatory, anti -apoptotic, and pro-growth factors of barbatimão, which could explain the efficacy of this herbal medicine in the healing of lesions.Introdução: A pele é o maior órgão do corpo humano e tem como funções revestir, delimitar, proteger e interagir com o meio exterior. As lesões na pele acometem a população de forma geral, independente de sexo, idade ou etnia e, em razão do alto índice de pessoas que apresentam alterações na integridade da pele, caracteriza-se em um sério problema de saúde pública. A cicatrização de lesões é considerada um processo de restauração da homeostase da pele, dinâmico e altamente coordenado, sendo que nos últimos anos têm-se verificado uma retomada à valorização de práticas terapêuticas com o uso de fitoterápicos no tratamento de diversas morbidades, incluindo a cicatrização de lesões cutânea. Muitas plantas já se mostraram promissoras, com destaque para o barbatimão (Stryphnodendron adstringens), e diversos estudos in vitroe in vivo já foram realizados demonstrando a ação cicatrizante e anti-inflamatória, entretanto os mecanismos relacionados ainda não foram esclarecidos. Objetivo: Analisar in vitro os mecanismos causais associados ao efeito cicatrizante do barbatimão (Stryphnodendron adstringens), bem como realizar revisão de literatura e analisar série de casos relacionados. Métodos: Inicialmente foi realizada uma análise integrada da literatura relacionada a propriedade cicatrizante do barbatimão, considerando os dados disponíveis nas principais plataformas científicas bem como a análise de uma série de casos. As cascas do barbatimão foram obtidas, e o extrato hidroalcoólico foi preparado e caracterizado quimicamente via Cromatografia Líquida de alta eficiência (HPLC). O extrato foi testado in vitro em duas linhagens celulares comerciais de queratinócitos (HaCaT) e fibroblastos (HFF-1), cultivadas em ambiente apropriado, foram realizadas as curvas farmacológicas, e uma vez definidas as concentrações de uso foram realizadas análises relacionadas a citotoxicidade e genotoxidade. Em um terceiro momento, células da linhagem HFF-1, integras e em modelo de lesão in vitro, tratadas com barbatimão nas concentrações de 0.49mg/mL e 0.99mg/mL por 24 ou 72 horas, das quais foi avaliado: (1) metabolismo oxidativo (oxidação do DNA, lipoperoxidação, carbonilação de proteinas, níveis das enzimas antioxidantes); (2) citocinas pró-inflamatórias (TNF-α, interleucina 6); (3) marcadores apoptóticos = Caspases (CASP) 3 e 8 e fatores de crescimento (KGF e FGF-1). Resultados: 42 publicações sobre barbatimão foram incluídas na revisão, a maioria publicada em língua inglesa. A partir desses estudos foi identificada descrição de diversas ações biológicas e clínicas do barbatimão, tais como efeitos antiinflamatórios, antioxidantes, antiulcerogênicos e antimicrobianos, antiparasitários, além de suas propriedades curativas. Relatamos uma série de casos de pacientes submetidos ao tratamento com barbatimão para cicatrização de lesões causadas por trauma físico involuntário intenso (acidentes externos) ou cirurgia. Considerando todos os casos, a duração completa da cicatrização ocorreu durante 3,6 ± 0,8 meses. Em relação ao estudo 2, os resultados demonstram que as principais moléculas bioativas quantificadas por HPLC foram ácido gálico, ácido cafeico, quercetina, catequina e epigalocatequina-3- gallato (EGCG). O barbatimão foi capaz de diminuir a mortalidade celular em comparação com grupo de controle, e ainda apresentou efeito genoprotetor ao DNA. No 3 estudo o tratamento com 0.49 mg/mL e 0.99 mg/mL, apresentou efeito redutor sobre os marcadores oxidativos, inflamatórios e apoptóticos, concomitantemente o barbatimão foi capaz de elevar os níveis de antioxidantes e fatores de crescimento. Conclusão: Tendo em vista a revisão de literartura, a série de casos, e nossos estudos in vitro, nossos resultados ainda que iniciais e com necessidade de serem complementados por mais estudos, dão fortes indicios da ação antioxidante, genoprotetora, anti-inflamatória, anti-apoptótica, e pró-fatores de crescimento do barbatimão, o que poderia explicar a eficácia deste fitoterápico na de cicatrização de lesões.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em FarmacologiaUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessInflamaçãoAntioxidanteFibroblastosQueratinócitosInflammationAntioxidantFibroblastsKeratinocytesCNPQ::CIENCIAS DA SAUDE::FARMACIAInvestigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitroResearch of mechanisms associated to the healing and regenerative effect of barbatimão (Stryphnodendron adstringens) in cellular models in vitroinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisDuarte, Marta Maria Medeiros Frescurahttp://lattes.cnpq.br/6277584896102052Oliveira, Beatriz Guitton Renaud Baptista dehttp://lattes.cnpq.br/5825896654509091Wagner, Glauberhttp://lattes.cnpq.br/8417542717418294Bochi, Guilherme Vargashttp://lattes.cnpq.br/4191221572795869Bauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968http://lattes.cnpq.br/5269363454655292Pellenz, Neida Luiza Kaspary4003000000056007eb9a3b5-0399-4f7a-9083-ade2caf7930529556dec-0bbf-4492-8c0a-e005b1d0419499a180f5-9bda-4f05-888d-384e9d7de89d5d7072f8-cb5d-4f65-a782-86ff77bc66c3c0b43446-70ce-4dba-b707-67745b718a362692a8bc-fe74-4278-b83e-83c3d8a4024dreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGFARMACOLOGIA_2019_PELLENZ_NEIDA .pdfTES_PPGFARMACOLOGIA_2019_PELLENZ_NEIDA .pdfTese de Doutoradoapplication/pdf6111709http://repositorio.ufsm.br/bitstream/1/20254/1/TES_PPGFARMACOLOGIA_2019_PELLENZ_NEIDA%20.pdf0f649b2cc07534fb74fb51a825d9cb80MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
dc.title.alternative.eng.fl_str_mv Research of mechanisms associated to the healing and regenerative effect of barbatimão (Stryphnodendron adstringens) in cellular models in vitro
title Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
spellingShingle Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
Pellenz, Neida Luiza Kaspary
Inflamação
Antioxidante
Fibroblastos
Queratinócitos
Inflammation
Antioxidant
Fibroblasts
Keratinocytes
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
title_full Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
title_fullStr Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
title_full_unstemmed Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
title_sort Investigação dos mecanismos associados ao efeito cicatrizante e regenerativo do barbatimão (Stryphnodendron adstringens) em modelos celulares in vitro
author Pellenz, Neida Luiza Kaspary
author_facet Pellenz, Neida Luiza Kaspary
author_role author
dc.contributor.advisor1.fl_str_mv Duarte, Marta Maria Medeiros Frescura
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6277584896102052
dc.contributor.referee1.fl_str_mv Oliveira, Beatriz Guitton Renaud Baptista de
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/5825896654509091
dc.contributor.referee2.fl_str_mv Wagner, Glauber
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/8417542717418294
dc.contributor.referee3.fl_str_mv Bochi, Guilherme Vargas
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/4191221572795869
dc.contributor.referee4.fl_str_mv Bauermann, Liliane de Freitas
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/5849925846135968
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5269363454655292
dc.contributor.author.fl_str_mv Pellenz, Neida Luiza Kaspary
contributor_str_mv Duarte, Marta Maria Medeiros Frescura
Oliveira, Beatriz Guitton Renaud Baptista de
Wagner, Glauber
Bochi, Guilherme Vargas
Bauermann, Liliane de Freitas
dc.subject.por.fl_str_mv Inflamação
Antioxidante
Fibroblastos
Queratinócitos
topic Inflamação
Antioxidante
Fibroblastos
Queratinócitos
Inflammation
Antioxidant
Fibroblasts
Keratinocytes
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Inflammation
Antioxidant
Fibroblasts
Keratinocytes
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Introduction: The skin is the largest organ of the human body and has the functions of coat, delimitate, protec and interact with the external environment. Skin lesions affect the general population, regardless of gender, age or ethnicity, and because of the high rate of people with changes in skin integrity, it is a serious public health problem. The healing of lesions is considered a process of restoration of the homeostasis of the skin, dynamic and highly coordinated, and in recent years there has been a resumption to the valorization of therapeutic practices with the use of herbal medicines in the treatment of various morbidities, including cicatrization of cutaneous lesions. Many plants have already shown promise, especially barbatimão (Stryphnodendron adstringens), several in vitro and in vivo studies have already been performed demonstrating the healing and anti-inflammatory action, however the related mechanisms have not yet been clarified. Objective: To analyze in vitro the causal mechanisms associated with the healing effect of barbatimão (Stryphnodendron adstringens), as well as to carry out literature review and analyze a series of related cases. Methods: Initially, an integrated analysis of the literature related to the healing properties of barbatimão was performed, considering the data available in the main scientific platforms as well as the analysis of a series of cases. The barbatimão shells were obtained, and the hydroalcoholic extract was prepared and characterized chemically via High Performance Liquid Chromatography (HPLC). The extract was tested in vitro in two commercial keratinocyte (HaCaT) and fibroblast (HFF-1) cell lines, grown in an appropriate environment, the pharmacological curves were performed, and once the concentrations of use were determined, analyzes were performed related to cytotoxicity and genotoxicity. In a third phase, the HFF-1 cells, integrals and in vitro lesion model, treated with barbatimão at concentrations of 0.49mg / mL and 0.99mg / mL for 24 or 72 hours, were evaluated: (1) oxidative metabolism (oxidation of DNA, lipoperoxidation, carbonylation of proteins, levels of antioxidant enzymes); (2) proinflammatory cytokines (TNF-α, interleukin 6); (3) apoptotic markers = Caspases (CASPs) 3 and 8 and growth factors (KGF and FGF-1). Results: 42 publications on barbatimão were included in the review, most published in English. From these studies a description of several biological and clinical actions of barbatimão was identified, such as anti - inflammatory, anti - oxidant, antiulcerogenic and antimicrobial effects, antiparasitics, and its curative properties. We report a series of cases of patients submitted to barbatimão for healing of injuries caused by intense involuntary physical trauma (external accidents) or surgery. Considering all cases, the complete duration of healing occurred for 3.6 ± 0.8 months. In relation to study 2, the results demonstrate that the main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin and epigallocatechin-3-gallate (EGCG). The barbatimão was able to decrease the cellular mortality in comparison with the control group, and still presented genoprotective effect to the DNA. In the third study, the treatment with 0.49 mg / mL and 0.99 mg / mL presented a reducing effect on the oxidative, inflammatory and apoptotic markers, concomitantly the barbatimão was able to raise the levels of antioxidants and growth factors. Conclusion: In view of the literature review, the case series, and our in vitro studies, our initial results, which need to be complemented by further studies, give strong indications of the antioxidant, genoprotective, anti-inflammatory, anti -apoptotic, and pro-growth factors of barbatimão, which could explain the efficacy of this herbal medicine in the healing of lesions.
publishDate 2019
dc.date.issued.fl_str_mv 2019-03-11
dc.date.accessioned.fl_str_mv 2021-01-15T12:09:56Z
dc.date.available.fl_str_mv 2021-01-15T12:09:56Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/20254
url http://repositorio.ufsm.br/handle/1/20254
dc.language.iso.fl_str_mv por
language por
dc.relation.cnpq.fl_str_mv 400300000005
dc.relation.confidence.fl_str_mv 600
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dc.rights.driver.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Farmacologia
dc.publisher.initials.fl_str_mv UFSM
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Farmacologia
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
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reponame_str Manancial - Repositório Digital da UFSM
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