Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway

J Pharm Pharmacol. 2020 Nov;72(11):1615-1628. doi: 10.1111/jphp.13338. Epub 2020 Aug 5.

Abstract

Objectives: This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats.

Methods: Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin.

Key findings: The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression.

Conclusion: The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy.

Keywords: Morus nigra fruit extract; cyanidin glycosides; diabetic nephropathy; oxidative stress; phenolic compounds; proinflammatory cytokines.

MeSH terms

  • Albuminuria / etiology
  • Albuminuria / metabolism
  • Albuminuria / prevention & control
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Down-Regulation
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Fruit
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology*
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Morus* / chemistry
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats, Wistar
  • Signal Transduction
  • Streptozocin
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Blood Glucose
  • Fibronectins
  • Hypoglycemic Agents
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Streptozocin