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Background: Diabetic nephropathy is defined as a progressive decline in glomerular filtration rate, accompanied by proteinuria. Betulinic acid (BA) employs in the treatment and management of diabetes. Objectives: This study was designed to evaluate the preventive effects of BA on streptozotocinnicotinamide (STZ-NA) induced diabetic nephropathy in male mouse. Materials and Methods: In this experimental study, 60 adult male NMRI mice (20-25 g) were obtained. Type 2 diabetes induced by intraperitoneal (IP) injection of a single dose of STZ (65 mg/kg) 15 minutes after an IP administration of NA (120 mg/kg). Then, mice were divided into six groups; control, diabetes, diabetes + BA (10, 20 and 40 mg/kg), and diabetes + metformin (200 mg/kg). Twenty-four hours after the last drug administrations, plasma samples were obtained and maintained at −20°C for albumin, blood urea nitrogen (BUN) and creatinine (Cr) measurements. Renal tissue was removed, fixed in 10% formalin solution and stained with hematoxylin and eosin. Results: Plasma albumin level decreased in diabetic mice (P < 0.05) and increased in diabetic BA 10, 20, 40 mg/kg and metformin treated mice versus to diabetes group. BUN increased in diabetes (P < 0.001), and administration of BA 10, 20, 40 mg/kg and metformin showed a significant decrease in BUN of diabetic treated mice. Plasma Cr levels increased in diabetes (P < 0.01) but, BA 10, 20, 40 mg/kg and metformin decreased this enhancement of plasma Cr levels. Renal histopathology indicated normal appearances reduced in diabetic mice and BA or metformin administration improved them. Conclusion: BA has a preventing effect on diabetic nephropathy by amelioration of plasma albumin, BUN, Cr and renal histology changes during diabetic situation.

Preventive effects of betulinic acid on streptozotocinnicotinamide induced diabetic nephropathy in male mouse