Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells

Food Chem Toxicol. 2009 Jun;47(6):1221-30. doi: 10.1016/j.fct.2009.02.015. Epub 2009 Feb 20.


The mitogen-activated protein kinases (MAPK) and nuclear factor kappaB (NF-kappaB) are involved in transduction cascades that play a key role in inflammatory response. We tested the ability of preselected natural polyphenolic extracts (grape seed, cocoa, sugar cane, oak, mangosteen and pomegranate) to modulate intestinal inflammation using human intestinal Caco-2 cells treated for 4h with these extracts and then stimulated by cytokines for 24 or 48h. The effect of polyphenolic extracts, at 50 micromol of gallic acid equivalent/l, was investigated on inflammation-related cellular events: (i) NF-kappaB activity (cells transfected with a NF-kappaB-luciferase construct), (ii) activation of Erk1/2 and JNK (western blotting), (iii) secretion of interleukin 8 (IL-8) (ELISA), (iv) secretion of prostaglandin (PG) E(2) (ELISA), (v) production of NO (Griess method). Results show that: (i) sugar cane, oak and pomegranate extracts inhibited NF-kappaB activity (from 1.6 to 1.9-fold) (P<0.001); (ii) pomegranate slightly inhibited Erk1/2 activation (1.3-fold) (P=0.008); (iii) oak and pomegranate decreased NO synthesis by 1.5-fold (P<0.001) and that of IL-8 by 10.3 and 6.7-fold respectively; (iv) pomegranate and cocoa decreased PGE(2) synthesis by 4.6 (P<0.0001) and 2.2-fold (P=0.001), respectively. We suggest that pomegranate extract could be particularly promising in dietary prevention of intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Copper / chemistry
  • Dinoprostone / biosynthesis
  • Enzyme Activation / drug effects
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Free Radicals / chemistry
  • Hemolysis / drug effects
  • Humans
  • Inflammation Mediators / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Lipoproteins, LDL / chemistry
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Oxidation-Reduction
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology
  • Plants / chemistry*
  • Polyphenols
  • Thiobarbituric Acid Reactive Substances


  • Amidines
  • Antioxidants
  • Flavonoids
  • Free Radicals
  • Inflammation Mediators
  • Interleukin-8
  • Lipoproteins, LDL
  • NF-kappa B
  • Phenols
  • Plant Extracts
  • Polyphenols
  • Thiobarbituric Acid Reactive Substances
  • Nitric Oxide
  • 2,2'-azobis(2-amidinopropane)
  • Copper
  • Mitogen-Activated Protein Kinases
  • Dinoprostone