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Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (pAPCs), numerous in the pancreas of nonobese diabetic (NOD) mice and playing an essential role in the autoimmune response of type 1 diabetes. The expression of the enzyme indoleamine 2,3-dioxygenase (IDO) is a critical factor for the tolerogenic activity of pAPCs, acting in the catabolism of tryptophan, providing metabolites that suppress the T cell effectors and induce T regulatory cells differentiation. Here we investigated the in vitro mechanisms of lyophilized aqueous extract from Passiflora alata leaves (LAEPAL) that modulates bone marrow-derived professional antigen-presenting cells (BM-pAPCs), affecting their ability to polarize T cells. A cell culture model was defined using mixed cultures of BM-pAPCs and T lymphocytes NOD mice with stressed MIN-6 cells as a source of pancreatic β cells antigens. We showed that the treatment with 300 µg/mL of LAEPAL induces a significant decrease in the CD4 and CD8 T effector lymphocytes proliferation from diabetic but not in non-diabetic mice, followed by a reduction of the IL-6 and IFN-γ cytokines release in the cell cultures supernatants. Moreover, we observed an increase of CD4 + CD25 + FoxP3 + Tregs in the cell cultures from diabetic mice. These results could be partially explained by the LAEPAL modulatory effects in BM-pAPCs, downregulating the CD86 co-stimulatory molecule expression, and increasing IDO-1 expression in F4/80+ BM-pAPCs. These results contribute to a better understanding of the polyphenols' immunomodulatory properties, meaning they could induce tolerogenic antigen-presenting cells, which could polarize T cells to a Treg profile and decrease the activity of CD4+ and CD8+ T effector cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Passiflora alata Curtis (P. alata) leaves have anti-inflammatory properties; the present study aimed to investigate the anti-diabetogenic properties of P. alata aqueous leaf extract. HPLC analysis identified the phenolic compounds catechin, epicatechin and rutin. The aqueous extract was administered for 30weeks to non-obese diabetic (NOD) mice presenting a decrease of 28.6% in diabetes incidence and the number of inflammatory cells in pancreatic islets, when compared with the control group (water). The P. alata group presented an antioxidant effect and decreased lipid peroxidation in the serum of NOD mice. Increased numbers of insulin-positive cells were also observed in the pancreatic islets of the treated group. The diabetic group exhibited higher levels in the glucose tolerance test and glycemic index, in comparison to the P. alata-treated group and non-diabetic control BALB/c mice. In addition, the P. alata extract reduced the percentage and the proliferation index of NOD mice lymphocytes submitted to in vitro dose/response mitogenic stimulation assays. These results suggest that the aqueous extract of P. alata has anti-inflammatory properties, contributing to the protection of beta cells in pancreatic islets in NOD mice, and presents potential for use a supporting approach to treat type 1 diabetes., (Copyright © 2016. Published by Elsevier B.V.)