Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy

Chem Biol Interact. 2014 Aug 5;219:64-75. doi: 10.1016/j.cbi.2014.05.011. Epub 2014 May 28.

Abstract

Diabetic nephropathy (DN) is a serious complication confronted by diabetic patients. Available data indicate that the development of DN is linked to inflammation. In this context, nuclear factor-kappa B (NF-κB) has received much attention. Ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione), found abundantly in plant extracts and fruits, possesses numerous medicinal properties. We investigated the nephroprotective effects of oral treatment of ellagic acid in high fat diet/low dose streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rats. Ellagic acid treatment for 16weeks post induction of diabetes significantly attenuated renal dysfunction and oxidative stress. Ellagic acid significantly inhibited the renal NF-кB activation. Moreover, ellagic acid significantly lowered renal pathology and suppressed transforming growth factor-beta (TGF-β) and fibronectin expressions in renal tissues. Ellagic acid also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α). In cultured rat NRK 52E proximal tubular epithelial cells, ellagic acid treatment inhibited high glucose-induced activation of NF-κB and pro-inflammatory cytokine synthesis. These results suggest that ellagic acid exhibited renal protective effect in diabetic rats partly through antihyperglycemia which was accompanied by attenuation of inflammatory processes via inhibition of NF-κB pathway.

Keywords: Ellagic acid; High fat diet; Inflammation; Renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / prevention & control
  • Ellagic Acid / pharmacology*
  • Ellagic Acid / therapeutic use
  • Fibronectins / analysis
  • Fibronectins / metabolism
  • Glomerular Filtration Rate / physiology
  • Interleukin-1beta / analysis
  • Interleukin-1beta / metabolism
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Oxidative Stress / physiology*
  • Rats, Wistar
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Fibronectins
  • Interleukin-1beta
  • Interleukin-6
  • NF-kappa B
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Ellagic Acid