Significance of propolis administration for homeostasis of CD4+CD25+ immunoregulatory T cells controlling hyperglycemia

In the present study, we examined the effect of ethanolic soluble derivative of propolis (EEP) extract on immunological function in diabetic mouse models with the aim of highlighting the role of regulatory T cell, the change of cell surface molecule, and in vivo productions of IFN-γ. Murine models of diabetes mellitus (DM) were created by injecting normal mice with S961 peptide. Normal BALB/c mice were injected intraperitoneally with peptide S961 300 mg/kg body weight (BW) twice a day for eight days. On day 15, the spleen was isolated; then, cell surface molecules and regulatory T cells were analyzed using flow cytometry. The histopathological changes were monitored in the liver of treated and control mice. Afterward, we tested the ability of propolis as an immunomodulator that initiate normality metabolism and homeostasis. The propolis decreased blood sugar levels and increased the number of naïve T cells expressing CD62L molecule by suppressing the development of effector cells in diabetic mice. However, the propolis stimulated development of effector cells, which was indicated by increasing the number of CD4(+)CD25(+) T cells in normal mice. Moreover, the propolis increased the production of IFN-γ in normal mice, whereas in mouse models of diabetes mellitus propolis tends to suppress the production of IFN-γ. The histological analysis of the liver shows that at a dose of 50-200 mg/kg BW propolis does not show a toxic effect so that the dose is categorized safe. Therefore, the ethanolic soluble derivative of propolis (EEP) extract warrant for further exploited as an antidiabetic agent that safe for human.