Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both?
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.jep.2011.06.021 http://hdl.handle.net/11449/18288 |
Resumo: | Ethnopharmacological relevance: Uncaria tomentosa (Willd.) DC (Rubiaceae) is a species native to the Amazon rainforest and surrounding tropical areas that is endowed with immunomodulatory properties and widely used around the world. In this study we investigated the immunomodulatory potential of Uncaria tomentosa (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes.Materials and methods: C57BL/6 male mice were injected with MLDS (40 mg/kg) and orally treated with UT at 10-400 mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and beta-cell insulin content were analyzed by HE and immunohistochemical staining, respectively, and measured by digital morphometry. Lymphocyte immunophenotyping and cytokine production were determined by flow cytometry analysis.Results: Treating the animals with 50-400 mg/kg of UT caused a significant reduction in the glycemic levels, as well as in the incidence of diabetes. The morphometric analysis of insulitis revealed a clear protective effect. Animals treated with UT at 400 mg/kg presented a higher number of intact islets and a significant inhibition of destructive insulitis. Furthermore, a significant protection against the loss of insulin-secreting presented beta-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400 mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in healthy animals. These same higher doses also increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the production of Th1 and Th2, with increased levels of IL-4 and IL-5.Conclusions: The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways. (C) 2011 Elsevier B.V. All rights reserved. |
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Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both?Uncaria tomentosaDiabetesRegulatory T cellsCytokineStreptozotocinEthnopharmacological relevance: Uncaria tomentosa (Willd.) DC (Rubiaceae) is a species native to the Amazon rainforest and surrounding tropical areas that is endowed with immunomodulatory properties and widely used around the world. In this study we investigated the immunomodulatory potential of Uncaria tomentosa (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes.Materials and methods: C57BL/6 male mice were injected with MLDS (40 mg/kg) and orally treated with UT at 10-400 mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and beta-cell insulin content were analyzed by HE and immunohistochemical staining, respectively, and measured by digital morphometry. Lymphocyte immunophenotyping and cytokine production were determined by flow cytometry analysis.Results: Treating the animals with 50-400 mg/kg of UT caused a significant reduction in the glycemic levels, as well as in the incidence of diabetes. The morphometric analysis of insulitis revealed a clear protective effect. Animals treated with UT at 400 mg/kg presented a higher number of intact islets and a significant inhibition of destructive insulitis. Furthermore, a significant protection against the loss of insulin-secreting presented beta-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400 mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in healthy animals. These same higher doses also increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the production of Th1 and Th2, with increased levels of IL-4 and IL-5.Conclusions: The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways. (C) 2011 Elsevier B.V. All rights reserved.São Paulo State Univ UNESP, Sch Med, Dept Pathol, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Dept Microbiol & Immunol, Biosci Inst, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Sch Med, Ctr Hematol, BR-18618000 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Chem, Dept Organ Chem, BR-21941909 Rio de Janeiro, BrazilOswaldo Cruz Fdn FIOCRUZ, Dept Nat Prod, Inst Pharmaceut Technol, BR-21041250 Rio de Janeiro, BrazilSão Paulo State Univ UNESP, Sch Med, Dept Pathol, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Dept Microbiol & Immunol, Biosci Inst, BR-18618000 São Paulo, BrazilSão Paulo State Univ UNESP, Sch Med, Ctr Hematol, BR-18618000 São Paulo, BrazilElsevier B.V.Universidade Estadual Paulista (Unesp)Universidade Federal do Rio de Janeiro (UFRJ)Oswaldo Cruz Fdn FIOCRUZDomingues, Alexandre [UNESP]Sartori, Alexandrina [UNESP]Golim, Márjorie de Assis [UNESP]Marino Valente, Ligia Mariada Rosa, Larissa Camargo [UNESP]Watanabe Ishikawa, Larissa Lumi [UNESP]Siani, Antonio CarlosViero, Rosa Marlene [UNESP]2014-05-20T13:51:14Z2014-05-20T13:51:14Z2011-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article635-642application/pdfhttp://dx.doi.org/10.1016/j.jep.2011.06.021Journal of Ethnopharmacology. Clare: Elsevier B.V., v. 137, n. 1, p. 635-642, 2011.0378-8741http://hdl.handle.net/11449/1828810.1016/j.jep.2011.06.021WOS:000295236700075WOS000295236700075.pdf49775724161295271453564171333848Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Ethnopharmacology3.1151,150info:eu-repo/semantics/openAccess2024-09-03T13:14:52Zoai:repositorio.unesp.br:11449/18288Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:14:52Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
title |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
spellingShingle |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? Domingues, Alexandre [UNESP] Uncaria tomentosa Diabetes Regulatory T cells Cytokine Streptozotocin |
title_short |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
title_full |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
title_fullStr |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
title_full_unstemmed |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
title_sort |
Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both? |
author |
Domingues, Alexandre [UNESP] |
author_facet |
Domingues, Alexandre [UNESP] Sartori, Alexandrina [UNESP] Golim, Márjorie de Assis [UNESP] Marino Valente, Ligia Maria da Rosa, Larissa Camargo [UNESP] Watanabe Ishikawa, Larissa Lumi [UNESP] Siani, Antonio Carlos Viero, Rosa Marlene [UNESP] |
author_role |
author |
author2 |
Sartori, Alexandrina [UNESP] Golim, Márjorie de Assis [UNESP] Marino Valente, Ligia Maria da Rosa, Larissa Camargo [UNESP] Watanabe Ishikawa, Larissa Lumi [UNESP] Siani, Antonio Carlos Viero, Rosa Marlene [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Federal do Rio de Janeiro (UFRJ) Oswaldo Cruz Fdn FIOCRUZ |
dc.contributor.author.fl_str_mv |
Domingues, Alexandre [UNESP] Sartori, Alexandrina [UNESP] Golim, Márjorie de Assis [UNESP] Marino Valente, Ligia Maria da Rosa, Larissa Camargo [UNESP] Watanabe Ishikawa, Larissa Lumi [UNESP] Siani, Antonio Carlos Viero, Rosa Marlene [UNESP] |
dc.subject.por.fl_str_mv |
Uncaria tomentosa Diabetes Regulatory T cells Cytokine Streptozotocin |
topic |
Uncaria tomentosa Diabetes Regulatory T cells Cytokine Streptozotocin |
description |
Ethnopharmacological relevance: Uncaria tomentosa (Willd.) DC (Rubiaceae) is a species native to the Amazon rainforest and surrounding tropical areas that is endowed with immunomodulatory properties and widely used around the world. In this study we investigated the immunomodulatory potential of Uncaria tomentosa (UT) aqueous-ethanol extract on the progression of immune-mediated diabetes.Materials and methods: C57BL/6 male mice were injected with MLDS (40 mg/kg) and orally treated with UT at 10-400 mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and beta-cell insulin content were analyzed by HE and immunohistochemical staining, respectively, and measured by digital morphometry. Lymphocyte immunophenotyping and cytokine production were determined by flow cytometry analysis.Results: Treating the animals with 50-400 mg/kg of UT caused a significant reduction in the glycemic levels, as well as in the incidence of diabetes. The morphometric analysis of insulitis revealed a clear protective effect. Animals treated with UT at 400 mg/kg presented a higher number of intact islets and a significant inhibition of destructive insulitis. Furthermore, a significant protection against the loss of insulin-secreting presented beta-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400 mg/kg) presented CD4(+) and CD8(+) T-cell values similar to those observed in healthy animals. These same higher doses also increased the number of CD4(+)CD25(+)Foxp3(+) regulatory T-cells. Moreover, the extract modulated the production of Th1 and Th2, with increased levels of IL-4 and IL-5.Conclusions: The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways. (C) 2011 Elsevier B.V. All rights reserved. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-09-01 2014-05-20T13:51:14Z 2014-05-20T13:51:14Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.jep.2011.06.021 Journal of Ethnopharmacology. Clare: Elsevier B.V., v. 137, n. 1, p. 635-642, 2011. 0378-8741 http://hdl.handle.net/11449/18288 10.1016/j.jep.2011.06.021 WOS:000295236700075 WOS000295236700075.pdf 4977572416129527 1453564171333848 |
url |
http://dx.doi.org/10.1016/j.jep.2011.06.021 http://hdl.handle.net/11449/18288 |
identifier_str_mv |
Journal of Ethnopharmacology. Clare: Elsevier B.V., v. 137, n. 1, p. 635-642, 2011. 0378-8741 10.1016/j.jep.2011.06.021 WOS:000295236700075 WOS000295236700075.pdf 4977572416129527 1453564171333848 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Ethnopharmacology 3.115 1,150 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
635-642 application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1810021373695754240 |