Suppression of age-related renal changes in NF-kappaB and its target gene expression by dietary ferulate

J Nutr Biochem. 2009 May;20(5):378-88. doi: 10.1016/j.jnutbio.2008.04.008. Epub 2008 Jul 26.

Abstract

Ferulate is a well-described natural antioxidant found in plants. It protects against cellular redox disruption and several oxidative stress-related diseases, including inflammation in animal studies. In this study, we examined ferulate for its ability to suppress redox-sensitive, proinflammatory NF-kappaB activation via NF-kappaB-inducing kinase (NIK)/IkappaB kinase (IKK) and mitogen-activated protein kinases (MAPKs) by reducing oxidative stress in aged rats. The experimental design was set as follows: Sprague-Dawley rats, ages 7 months (young) and 20 months (old) were used in this study, and dietary ferulate (0.01% or 0.02%) was fed to the old rats for 10 days. Data show that in aged kidney tissue, ferulate exhibited its antioxidative action by maintaining redox regulation, suppressing NF-kappaB activation and modulating the expression of NF-kappaB-induced, proinflammatory COX-2, iNOS, VCAM-1 and ICAM-1. Next, we examined cultured YPEN-1 endothelial cells and show that ferulate protected YPEN-1 cells against tert-butylhydroperoxide-induced oxidative stress. The molecular modulation of NF-kappaB by ferulate was further revealed in endothelial YPEN-1 cells through ferulate's ability to suppress the activation of NIK/IKK and MAPKs. Based on these results, we conclude that ferulate's antioxidative capacity suppressed the age-related increase in NF-kappaB activity through inhibition of NIK/IKK and MAPKs in vivo. This study may also suggest the potentiality of ferulate as a developable supplement against chronic inflammatory disease as well as aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / physiology
  • Animals
  • Coumaric Acids / pharmacology*
  • Diet
  • Gene Expression Regulation / drug effects
  • I-kappa B Kinase / biosynthesis
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • NF-kappa B / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Protein Serine-Threonine Kinases / biosynthesis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Coumaric Acids
  • NF-kappa B
  • ferulic acid
  • Protein Serine-Threonine Kinases
  • I-kappa B Kinase
  • NF-kappa B kinase