en Cell, Stem Cell and Cancer Cell, Stem Cell and Cancer Experimental research article Experimental research article <div style="text-align: justify;"><strong>Introduction:</strong> Ursolic acid (UA) is a triterpenoid compound which widely found in the apple&rsquo;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&rsquo;s pancreas. <strong>Methods:</strong> 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. <strong>Results:</strong> Our findings obviously showed that UA enhanced SIRT1 (4&plusmn;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&plusmn;12 mg/dl to 149.75&plusmn;11 mg/dl. Moreover, we found that UA increased &beta;-cell numbers and islet Langerhans diameters (~2 folds). <strong>Conclusion:</strong> Our results provide valuable information not only into the mechanisms underlying &beta;-cells protection but also into the regulation of SIRT1 as a main target to attenuate &beta;-cells damage. Therefore, UA is a promising pharmacological therapeutic target for &beta;-cell regeneration through enhancing of SIRT1 over-expression.</div> SIRT1, Ursolic acid, Diabetes. 21 27 http://ppj.phypha.ir/browse.php?a_code=A-10-792-5&slc_lang=en&sid=1 Rozita Naseri Rozita.Naseri@kums.c.ir 3200319475328460029530 3200319475328460029530 No Department of Endocrinology and Metabolism, Kermanshah University of Medical Sciences, Kermanshah, Iran Fatemeh Bakhtiari fateme.bakhtiari@kums.c.ir 3200319475328460029531 3200319475328460029531 No Department of Internal- Medicine, Faculty of Medical-sciences, Medical University of Kermanshah, Kermanshah, Iran Cyrus Jalili cjalili@kums.ac.ir 3200319475328460029532 3200319475328460029532 No Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Nuredin Bakhtiari nuredin.bakhtiary@modares.ac.ir 3200319475328460029533 3200319475328460029533 Yes Department of Biochemistry, Faculty of Biological Sciences, North-Tehran Branches, Islamic Azad university, Tehran, Iran Introduction Diabetes is classified into two main categories based on the clinical presentation and pathophysiology. Type 1 diabetes is characterized by autoimmune β cell destruction. Conversely, type 2 diabetes is caused by a relative insulin deficiency in the face of insulin resistance. Interestingly, recent evidence suggests that silent mating type information regulation 2 homolog1 (SIRT1) modulates immune homeostasis and protection against autoimmunity through inducing of forkhead box P3 (FOXP3) and thereby influences Treg cell development (van Loosdregt et al., 2011). SIRT1 functions as class III histone deacetylases, binding to NAD+ and Physiology Physiology Physiology Physiology Physiology Physiology and PharmacologyPharmacology Pharmacology Pharmacology Pharmacology Physiol Pharmacol 23 (2019) 21-27 www.phypha.ir/ppj Abstract 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. iD