title: Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both?
abstract: BACKGROUND
  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.
  
  
  METHODS
  C57BL/6 male mice were injected with MLDS (40 mg/kg) and orally treated with UT at 10-400mg/kg during 21 days. Control groups received MLDS alone or the respective dilution vehicle. Pancreatic mononuclear infiltrate and β-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 50-400mg/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 400mg/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 β-cells was achieved, as observed by a careful immunohistochemical evaluation. The phenotypic analysis indicated that the groups treated with higher doses (100-400mg/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.
authors: Department of Pathology, Medical School, São Paulo State University (UNESP), Botucatu, São Paulo 18618-000, Brazil. domingues1@gmail.com
authors: Alexandre
authors: A
authors: Domingues
authors: Alexandrina
authors: A
authors: Sartori
authors: Marjorie Assis
authors: MA
authors: Golim
authors: Ligia Maria Marino
authors: LM
authors: Valente
authors: Larissa Camargo
authors: LC
authors: da Rosa
authors: Larissa Lumi Watanabe
authors: LL
authors: Ishikawa
authors: Antonio Carlos
authors: AC
authors: Siani
authors: Rosa Marlene
authors: RM
authors: Viero
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D020948:Cat's Claw / Q000737:chemistry; D016764:Cell Polarity / Q000187:drug effects*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000737:chemistry; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007150:Immunohistochemistry; D016130:Immunophenotyping / Q000379:methods; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012997:Solvents / Q000737:chemistry; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007004:Hypoglycemic Agents; C508018:Il2ra protein, mouse; D007328:Insulin; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D010936:Plant Extracts; D012997:Solvents; D014867:Water; D015847:Interleukin-4; D000431:Ethanol