Naringin ameliorates diabetic nephropathy by inhibiting NADPH oxidase 4

Eur J Pharmacol. 2017 Jun 5:804:1-6. doi: 10.1016/j.ejphar.2017.04.006. Epub 2017 Apr 7.

Abstract

Naringin, a naturally flavanone glycoside, has been previously demonstrated to alleviate diabetic kidney disease by inhibiting oxidative stress and inflammatory reaction. However, the underlying mechanism of naringin in diabetic nephropathy (DN) has not been fully elucidated. Here, the beneficial effect of naringin on DN in streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes and its underlying mechanism were elaborated. The result revealed that naringin alleviated STZ-induced renal dysfunction and injury in DN rats, relieved STZ-induced oxidative stress in vivo and inhibited HG-induced apoptosis and reactive oxygen species level i20n vitro. More importantly, naringin inhibited NOX4 expression at mRNA and protein levels in STZ-induced DN rats and HG-induced podocytes. Loss of function indicated that NADPH oxidases 4 (NOX4) down-regulation suppressed apoptosis and reactive oxygen species level in HG-treated podocytes. Take together, this study demonstrated that naringin ameliorates diabetic nephropathy by inhibiting NOX4, contributing to a better understanding of the progression of DN.

Keywords: Diabetic nephropathy; NOX4; Naringin; Oxidative stress; Reactive oxygen species.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / enzymology*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Flavanones / pharmacology*
  • Flavanones / therapeutic use
  • Gene Expression Regulation, Enzymologic / drug effects
  • Kidney / drug effects
  • Kidney / injuries
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • NADPH Oxidase 4
  • NADPH Oxidases / antagonists & inhibitors*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Oxidative Stress / drug effects
  • Podocytes / drug effects
  • Podocytes / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • Enzyme Inhibitors
  • Flavanones
  • RNA, Messenger
  • Reactive Oxygen Species
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, rat
  • naringin