Ursolic acid enhances the cellular immune system and pancreatic beta-cell function in streptozotocin-induced diabetic mice fed a high-fat diet

This study investigated the effects of ursolic acid on immunoregulation and pancreatic beta-cell function in type 1 diabetes fed a high-fat diet for 4 weeks. Male mice were divided into non-diabetic, diabetic control, and diabetic-ursolic acid (0.05%, w/w) groups, which were fed a high-fat (37% calories from fat). Diabetes was induced by injection of streptozotocin (200 mg/kg B.W., i.p.). Ursolic acid significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. The plasma insulin and C-peptide concentrations were significantly higher in the diabetic-ursolic acid group than in the diabetic group. Ursolic acid significantly elevated the insulin levels with preservation of insulin staining of beta-cells in the pancreas. In splenocytes, concanavalin (Con) A-induced T-cell proliferation was significantly higher in the diabetic-ursolic acid group compared to the diabetic group, but liposaccharide (LPS)-induced B-cell proliferation did not differ between groups. Ursolic acid enhanced IL-2 and IFN-gamma production in response to Con A stimulation, whereas it inhibited TNF-alpha production in response to LPS stimulation. In this study, neither streptozotocin nor ursolic acid had effects on lymphocyte subsets. These results indicate that ursolic acid exhibits potential anti-diabetic and immunomodulatory properties by increasing insulin levels with preservation of pancreatic beta-cells and modulating blood glucose levels, T-cell proliferation and cytokines production by lymphocytes in type 1 diabetic mice fed a high-fat diet. (C) 2008 Elsevier B.V. All rights reserved.