Background: Type 2 Diabetes Mellitus (T2DM) accounts for about 90% of diabetic cases. Diabetic Nephropathy (DN) is one of the most serious complications of diabetes. Sitagliptin has an important role in enhancement the Glucagon-Like Peptide (GLP-1) and its receptor (GLP-1R) which present in the kidneys, so it may have a role in the modulation of kidney function in T2DM. Also Punica Granatum Peels Extract (PGPE) is an herbal drug which has anti-hyperglycemic and antioxidant activities.

Objective: This study was designed to investigate if PGPE and/or sitagliptin could improve renal functions in DN.

Materials and Methods: The current study was performed on 60 adult male albino rats. Their body weight ranged from 200 to 250 grams. Rats were divided into two main groups: Group I” normal control animals” consists of 20 rats (divided into group1: normal control and group2: vehicle received control) 10 rats / each. Group II “Diabetic animals” consist of 40 rats were divided into 4 treated groups: (Diabetic, PGPE, Sitagliptin, sitagliptin and PGPE) 10 rats / each. At the end of experimental period (6 weeks), urinary protein, Fasting Blood Glucose (FBG), serum urea, Blood Urea Nitrogen (BUN), creatinine, renal lipid peroxidation (MDA), Tumor Necrosis Factor Alpha (TNFα), antioxidant enzymes and histopathology were assessed.

Results: Increase in FBG, serum urea, BUN & creatinine, 24 hours urinary protein, renal MDA & TNFα with decrease in antioxidant enzymes activity and degenerated tubules & mononuclear cell infiltration as revealed by histopathological examination confirmed the manifestation of DN. Simultaneous administration of PGPE and sitagliptin protected kidney against DN as evidenced from improvement of renal functions parameters and amelioration of histopathological finding.

Conclusion: The results of our study thus prove the protective effect of PGPE with sitagliptin in early diabetic nephropathy.