Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3'-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages

Biochem Pharmacol. 2000 Feb 15;59(4):357-67. doi: 10.1016/s0006-2952(99)00335-4.

Abstract

We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Biflavonoids*
  • Catechin
  • Cells, Cultured
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids*
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Gene Expression / drug effects
  • Glucosides / pharmacology
  • Hydrolyzable Tannins*
  • I-kappa B Kinase
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Phenols / pharmacology*
  • Phosphorylation
  • Polymers / pharmacology*
  • Polyphenols
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Tannins / pharmacology
  • Tea / chemistry

Substances

  • Antioxidants
  • Biflavonoids
  • Enzyme Inhibitors
  • Flavonoids
  • Glucosides
  • Hydrolyzable Tannins
  • Lipopolysaccharides
  • NF-kappa B
  • Phenols
  • Polymers
  • Polyphenols
  • Tannins
  • Tea
  • Nitric Oxide
  • theaflavin digallate
  • pentagalloylglucose
  • Geraniin
  • Gallic Acid
  • Catechin
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Protein Serine-Threonine Kinases
  • Chuk protein, mouse
  • I-kappa B Kinase
  • Ikbkb protein, mouse
  • Ikbke protein, mouse