Flavonoid rich fraction of Punica granatum improves early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals

Pharm Biol. 2015 Jan;53(1):61-71. doi: 10.3109/13880209.2014.910533. Epub 2014 Oct 7.


Context: Different parts of Punica granatum Linn. (Punicaceae) are traditionally used as renal protective agents in the Indian system of medicine. However, there is paucity of information regarding its role in diabetic nephropathy.

Objective: The present study investigates the nephroprotective potential of flavonoid-rich fraction of P. granatum leaves in streptozotocin (STZ)-induced early diabetic nephropathy in experimental animals.

Materials and methods: Experimental diabetic nephropathy was induced in Wistar rats by single intraperitonial injection of STZ (65 mg/kg) dissolved in ice cold citrophosphate buffer (pH 4.3). After induction rats were divided into five groups (6 normal; 24 diabetic) and administered with glibenclamide (5 mg/kg) and three dose levels of flavonoid-rich fraction of P. granatum leaves (PGFF), i.e. 50, 100, and 200 mg/kg body weight/day for 28 d. Fasting blood glucose, lipid profile, serum albumin, serum total protein, serum creatinine, blood urea nitrogen (BUN) glycosylated hemoglobin, and biomarkers of kidney oxidative stress were assessed at the end of the treatment period. Urine was analyzed for the measurement of total protein, albumin, and creatinine clearance. Kidney sections were subjected to histopathological study.

Results: Daily oral administration of variable dose levels of PGFF for 28 d normalized various biochemical, metabolic, and histopathological changes in the diabetic rats. PGFF significantly (p < 0.01 and p < 0.05) improved the glycemic status and renal function in diabetic rats as compared with diabetic control rats.

Discussion and conclusion: The results of our study thus prove the protective effect of PGFF in early diabetic nephropathy by ameliorating proteinuria and disturbed glucose homeostasis in experimental animals.

Keywords: Antihyperglycemic; antihyperlipidemic; antioxidant; quercetin; renal protective; streptozotocin; traditional herbal medicine.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Female
  • Flavonoids / isolation & purification
  • Flavonoids / therapeutic use*
  • Flavonoids / toxicity
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Homeostasis / drug effects
  • Kidney / drug effects
  • Kidney / pathology
  • Lipids / blood
  • Lythraceae / chemistry*
  • Male
  • Oxidative Stress / drug effects
  • Plant Leaves / chemistry
  • Proteinuria / metabolism
  • Proteinuria / pathology
  • Proteinuria / prevention & control*
  • Rats, Wistar


  • Biomarkers
  • Blood Glucose
  • Flavonoids
  • Lipids
  • Glucose