Ursolic acid increases SIRT1 protein level and β-cells number in diabetic rats

Introduction: Ursolic acid (UA) is a triterpenoid compound which widely found in the apple’s peel. It has wide health-promoting properties; as previous studies properly indicated to its abilities. In this scenario our attention has been paid to the application of UA as an anti-diabetic compound. Based on our recent studies in relating to SIRT1 protein/gene and UA, the aim of this research was to evaluate UA effects on the SIRT1 expression in diabetic rat’s pancreas. Methods: In this study we used 20 male diabetic wistar rats. To develop diabetic rats, they received 30mg/kg of streptozotocin for 2 days sequentially. Then, they classified to 2 groups, the ones received UA + corn oil twice daily for two weeks and others (the control group) just received corn oil. Results: Our findings obviously showed that UA enhanced SIRT1 (4±0.2 folds) proteins levels in pancreas (P<0.001), in comparison with control rats. In addition, the findings showed that UA significantly decreased fasting blood glucose from 416.17±12 mg/dl to 149.75±11 mg/dl. Moreover, we found that UA increased β- cell numbers and islet Langerhans diameters (~2 folds). Conclusion: Our results provide valuable information not only into the mechanisms underlying β-cells protection but also into the regulation of SIRT1 as a main target to attenuate β-cells damage. Therefore, UA is a promising pharmacological therapeutic target for β-cell regeneration through enhancing of SIRT1 over-expression.