Prevention of experimental diabetes by Uncaria tomentosa extract: Th2 polarization, regulatory T cell preservation or both?

Abstract

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. 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. 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. The extract was effective to prevent the progression of immune-mediated diabetes by distinct pathways.