Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/7133 |
Resumo: | Psoriasis is an autoimmune, chronic inflammatory disease, affecting 2-3% of the world population. In the early stages of the disease onset, studies have shown chemerin as a triggering protein playing a key role. Brazilian national essential medicines list (RENAME) proposed the topic usage of Aloe vera barbadensis extract as a therapeutic approach for psoriasis for its immunomodulatory and anti-inflammatory effects. In order to investigate them, we adopted an In Vivo murine model with phenotype similar to psoriasis via topical application of imiquimod (IMQ) and treating animals with 70% Aloe vera cream for further comparison with controls. In addition, animal skin biopsies were tested for the enzymatic activity of the myeloperoxidase (MPO) as an indicator of neutrophil activity. As In Vitro model it was used an immortalized keratinocyte cell line to assess the wound healing potential of the Aloe vera freeze dried extract 200:1 (AVFDE) via Scratch Assay. Later, primary human dermal fibroblasts were used to evaluate the potential modulation on constitutive expression of chemerin and three proinflammatory cytokines. Culture supernatants of dermal fibroblasts were assessed against AVFDE and five of its phytoconstituents including the polyssacharide Acemannan (ACM). For this, we used ELISA and flow cytometry. We partially reproduced In Vivo human psoriatic phenotype in mice via IMQ induction and the MPO activity was shown to be lower in animals treated topically with 70% Aloe vera cream. It was observed in the In Vitro experiments that AVFDE 50ug/ml reduced the expression of MCP-1 chemokine and the concentration of 250ug/ml increased IL-8 expression. ACM 250ug/ml increased the expression levels of IL-8 and IL-6. Acemannan (ACM) at the two tested concentrations significantly reduced chemerin expression. Aloeresin A 20uM increased IL-6 expression. Either tested phytosterol, at any concentration range elicited effects on the expression levels of cytokines or chemerin. The results suggested that the therapeutic usage of Aloe vera extract as an immunomodulatory and / or anti inflammatory agent must be further evaluated. Although the extract demonstrated a potential benefit in the treatment of early stages of psoriasis it is essential that commercial plant extracts are standardized with a minimum content of bioactive phytocompounds as Acemannan within the marketed pharmaceutical formulations as stated by related regulatory organisms. |
id |
UFES_8532a26c99e786e2f2999559298595e0 |
---|---|
oai_identifier_str |
oai:repositorio.ufes.br:10/7133 |
network_acronym_str |
UFES |
network_name_str |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
repository_id_str |
2108 |
spelling |
Sze, Daniel Man-YuenRangel, Leticia Batista AzevedoPiva, Terrence J.Amorim, Gustavo Modesto deErrera, Flavia Imbroisi ValleGuimarães, Marco Cesar CunegundesKuster, Ricardo MachadoGouvea, Sonia Alves2018-08-01T21:35:18Z2018-08-012018-08-01T21:35:18Z2016-07-21Psoriasis is an autoimmune, chronic inflammatory disease, affecting 2-3% of the world population. In the early stages of the disease onset, studies have shown chemerin as a triggering protein playing a key role. Brazilian national essential medicines list (RENAME) proposed the topic usage of Aloe vera barbadensis extract as a therapeutic approach for psoriasis for its immunomodulatory and anti-inflammatory effects. In order to investigate them, we adopted an In Vivo murine model with phenotype similar to psoriasis via topical application of imiquimod (IMQ) and treating animals with 70% Aloe vera cream for further comparison with controls. In addition, animal skin biopsies were tested for the enzymatic activity of the myeloperoxidase (MPO) as an indicator of neutrophil activity. As In Vitro model it was used an immortalized keratinocyte cell line to assess the wound healing potential of the Aloe vera freeze dried extract 200:1 (AVFDE) via Scratch Assay. Later, primary human dermal fibroblasts were used to evaluate the potential modulation on constitutive expression of chemerin and three proinflammatory cytokines. Culture supernatants of dermal fibroblasts were assessed against AVFDE and five of its phytoconstituents including the polyssacharide Acemannan (ACM). For this, we used ELISA and flow cytometry. We partially reproduced In Vivo human psoriatic phenotype in mice via IMQ induction and the MPO activity was shown to be lower in animals treated topically with 70% Aloe vera cream. It was observed in the In Vitro experiments that AVFDE 50ug/ml reduced the expression of MCP-1 chemokine and the concentration of 250ug/ml increased IL-8 expression. ACM 250ug/ml increased the expression levels of IL-8 and IL-6. Acemannan (ACM) at the two tested concentrations significantly reduced chemerin expression. Aloeresin A 20uM increased IL-6 expression. Either tested phytosterol, at any concentration range elicited effects on the expression levels of cytokines or chemerin. The results suggested that the therapeutic usage of Aloe vera extract as an immunomodulatory and / or anti inflammatory agent must be further evaluated. Although the extract demonstrated a potential benefit in the treatment of early stages of psoriasis it is essential that commercial plant extracts are standardized with a minimum content of bioactive phytocompounds as Acemannan within the marketed pharmaceutical formulations as stated by related regulatory organisms.Psoríase é uma doença inflamatória crônica, autoimune que atinge 2-3% da população mundial. Nas fases iniciais de desencadeamento da doença, estudos mostram que a proteína chemerina exerce um papel fundamental. A Relação Nacional de Medicamentos Essenciais (RENAME) propõe o uso tópico com fins terapêuticos do extrato vegetal da Aloe vera barbadensis contra a psoríase por suas propriedades imunomoduladoras e anti inflamatórias. Para investigação de tais efeitos, o presente trabalho reproduziu um modelo murino In Vivo com fenótipo semelhante à psoríase via aplicação tópica do fármaco imiquimode (IMQ), tratando os animais com creme de Aloe vera à 70% e comparando-os aos controles. Adicionalmente, biopsias da pele dos animais foram testadas quanto à atividade enzimática da mieloperoxidase (MPO) como indicativo de atividade neutrofílica. O modelo In Vitro, utilizou linhagens celulares de queratinócitos imortalizados para avaliação do potencial cicatricional do extrato concentrado 200:1 em pó liofilizado (AVFDE) via Ensaio do Arranhão. Fibroblastos primários dermais humanos foram usados para avaliar o potencial modulador sobre a expressão constitutiva da chemerina e de três citocinas pró-inflamatórias em seus sobrenadantes frente ao uso de AVFDE e cinco fitoconstituintes incluindo o polissacarídeo Acemannan (ACM). Para tal, empregou-se o método ELISA e a citometria de fluxo. O fenótipo psoríasico humano em camundongos via indução por IMQ foi parcialmente reproduzido. A atividade (MPO) mostrou-se menor em animais tratados topicamente com o creme de Aloe vera à 70%. In Vitro observou-se que o AVFDE 50ug/ml reduziu a expressão da quimiocina MCP-1 e à 250ug/ml elevou a expressão de IL-8. ACM 250ug/ml aumentou os níveis de expressão de IL-8 e IL-6. Acemannan (ACM) nas duas concentrações testadas reduziu significativamente a expressão de chemerina. Aloeresina A na concentração 20uM elevou a expressão de IL6. Nenhum fitoesterol nas concentrações testadas elicitou efeitos sobre os níveis de expressão das citocinas ou da chemerina. Os resultados sugerem que o uso terapêutico com objetivos imunoestimulador e anti inflamatório do extrato do Aloe vera precisa ser melhor avaliado, mas demonstra potencial no tratamento nas fases iniciais da psoríase desde que sejam padronizados os teores mínimos de fitocompostos bioativos como o Acemannan nas apresentações farmacêuticas comercializadas.Texthttp://repositorio.ufes.br/handle/10/7133porUniversidade Federal do Espírito SantoDoutorado em BiotecnologiaPrograma de Pós-Graduação em BiotecnologiaUFESBRCentro de Ciências da SaúdePsoriasisChemerinAloeresin and acemannanPsoríaseAloe veraChemerinaAloeresina e acemannanBiotecnologia61Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALtese_10327_Tese Doutorado_Gustavo Amorim.pdfapplication/pdf3119115http://repositorio.ufes.br/bitstreams/750a96a2-9b55-4d91-8980-e70ecc238072/download22a0653efe37fa5044f9c17c7a071cfeMD5110/71332024-08-27 13:05:15.777oai:repositorio.ufes.br:10/7133http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-10-15T17:57:03.948304Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
title |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
spellingShingle |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo Amorim, Gustavo Modesto de Psoriasis Chemerin Aloeresin and acemannan Psoríase Aloe vera Chemerina Aloeresina e acemannan Biotecnologia 61 |
title_short |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
title_full |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
title_fullStr |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
title_full_unstemmed |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
title_sort |
Bioatividade de fitocompostos da Aloe vera barbadensis em modelos de psoríase In Vitro e In Vivo |
author |
Amorim, Gustavo Modesto de |
author_facet |
Amorim, Gustavo Modesto de |
author_role |
author |
dc.contributor.advisor-co1.fl_str_mv |
Sze, Daniel Man-Yuen |
dc.contributor.advisor1.fl_str_mv |
Rangel, Leticia Batista Azevedo |
dc.contributor.advisor2.fl_str_mv |
Piva, Terrence J. |
dc.contributor.author.fl_str_mv |
Amorim, Gustavo Modesto de |
dc.contributor.referee1.fl_str_mv |
Errera, Flavia Imbroisi Valle |
dc.contributor.referee2.fl_str_mv |
Guimarães, Marco Cesar Cunegundes |
dc.contributor.referee3.fl_str_mv |
Kuster, Ricardo Machado |
dc.contributor.referee4.fl_str_mv |
Gouvea, Sonia Alves |
contributor_str_mv |
Sze, Daniel Man-Yuen Rangel, Leticia Batista Azevedo Piva, Terrence J. Errera, Flavia Imbroisi Valle Guimarães, Marco Cesar Cunegundes Kuster, Ricardo Machado Gouvea, Sonia Alves |
dc.subject.eng.fl_str_mv |
Psoriasis Chemerin Aloeresin and acemannan |
topic |
Psoriasis Chemerin Aloeresin and acemannan Psoríase Aloe vera Chemerina Aloeresina e acemannan Biotecnologia 61 |
dc.subject.por.fl_str_mv |
Psoríase Aloe vera Chemerina Aloeresina e acemannan |
dc.subject.cnpq.fl_str_mv |
Biotecnologia |
dc.subject.udc.none.fl_str_mv |
61 |
description |
Psoriasis is an autoimmune, chronic inflammatory disease, affecting 2-3% of the world population. In the early stages of the disease onset, studies have shown chemerin as a triggering protein playing a key role. Brazilian national essential medicines list (RENAME) proposed the topic usage of Aloe vera barbadensis extract as a therapeutic approach for psoriasis for its immunomodulatory and anti-inflammatory effects. In order to investigate them, we adopted an In Vivo murine model with phenotype similar to psoriasis via topical application of imiquimod (IMQ) and treating animals with 70% Aloe vera cream for further comparison with controls. In addition, animal skin biopsies were tested for the enzymatic activity of the myeloperoxidase (MPO) as an indicator of neutrophil activity. As In Vitro model it was used an immortalized keratinocyte cell line to assess the wound healing potential of the Aloe vera freeze dried extract 200:1 (AVFDE) via Scratch Assay. Later, primary human dermal fibroblasts were used to evaluate the potential modulation on constitutive expression of chemerin and three proinflammatory cytokines. Culture supernatants of dermal fibroblasts were assessed against AVFDE and five of its phytoconstituents including the polyssacharide Acemannan (ACM). For this, we used ELISA and flow cytometry. We partially reproduced In Vivo human psoriatic phenotype in mice via IMQ induction and the MPO activity was shown to be lower in animals treated topically with 70% Aloe vera cream. It was observed in the In Vitro experiments that AVFDE 50ug/ml reduced the expression of MCP-1 chemokine and the concentration of 250ug/ml increased IL-8 expression. ACM 250ug/ml increased the expression levels of IL-8 and IL-6. Acemannan (ACM) at the two tested concentrations significantly reduced chemerin expression. Aloeresin A 20uM increased IL-6 expression. Either tested phytosterol, at any concentration range elicited effects on the expression levels of cytokines or chemerin. The results suggested that the therapeutic usage of Aloe vera extract as an immunomodulatory and / or anti inflammatory agent must be further evaluated. Although the extract demonstrated a potential benefit in the treatment of early stages of psoriasis it is essential that commercial plant extracts are standardized with a minimum content of bioactive phytocompounds as Acemannan within the marketed pharmaceutical formulations as stated by related regulatory organisms. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-07-21 |
dc.date.accessioned.fl_str_mv |
2018-08-01T21:35:18Z |
dc.date.available.fl_str_mv |
2018-08-01 2018-08-01T21:35:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufes.br/handle/10/7133 |
url |
http://repositorio.ufes.br/handle/10/7133 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Doutorado em Biotecnologia |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biotecnologia |
dc.publisher.initials.fl_str_mv |
UFES |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Doutorado em Biotecnologia |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) instname:Universidade Federal do Espírito Santo (UFES) instacron:UFES |
instname_str |
Universidade Federal do Espírito Santo (UFES) |
instacron_str |
UFES |
institution |
UFES |
reponame_str |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
collection |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
bitstream.url.fl_str_mv |
http://repositorio.ufes.br/bitstreams/750a96a2-9b55-4d91-8980-e70ecc238072/download |
bitstream.checksum.fl_str_mv |
22a0653efe37fa5044f9c17c7a071cfe |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 |
repository.name.fl_str_mv |
Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES) |
repository.mail.fl_str_mv |
|
_version_ |
1813022539765514240 |