Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model

J Nutr. 1998 Dec;128(12):2334-40. doi: 10.1093/jn/128.12.2334.


Green tea polyphenols are potent antioxidants. They have both anti-cancer and anti-inflammatory effects. However, their mechanisms of actions remain unclear. In inflammation, tumor necrosis factor-alpha(TNFalpha) plays a pivotal role. NF-KB, an oxidative stress -sensitive nuclear transcription factor, controls the expression of many genes including the TNFalpha gene. We postulated that green tea polyphenols regulate TNFalpha gene expression by modulating NF-KB activation through their antioxidant properties. In the macrophage cell line, RAW264.7, (-)epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNFalpha production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFalpha mRNA expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFalpha production in elicited mouse peritoneal macrophages. In male BALB/c mice, green tea polyphenols (given by oral gavage 2 h prior to an i.p. injection of 40 mg LPS/kg body wt) decreased LPS-induced TNFalpha production in serum in a dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt, serum TNFalpha was reduced by 80% of control. Moreover, 0.5 g green tea polyphenols/kg body wt completely inhibited LPS-induced lethality in male BALB/c mice. We conclude that the anti-inflammatory mechanism of green tea polyphenols is mediated at least in part through down-regulation of TNFalpha gene expression by blocking NF-KB activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / pharmacology*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line
  • Disease Models, Animal
  • Down-Regulation
  • Flavonoids*
  • Gene Expression Regulation / drug effects*
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / toxicity
  • Macrophages, Peritoneal / drug effects
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / drug effects*
  • NF-kappa B / metabolism
  • Phenols / isolation & purification
  • Phenols / metabolism
  • Phenols / pharmacology*
  • Polymers / isolation & purification
  • Polymers / metabolism
  • Polymers / pharmacology*
  • Tea / chemistry*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Flavonoids
  • Lipopolysaccharides
  • NF-kappa B
  • Phenols
  • Polymers
  • Tea
  • Tumor Necrosis Factor-alpha
  • Catechin
  • epigallocatechin gallate