Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model.
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.
Yang
F
F
Graduate Program in Nutritional Sciences, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536, USA.
de Villiers
W J
WJ
McClain
C J
CJ
Varilek
G W
GW
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation; D005419:Flavonoids; D005786:Gene Expression Regulation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011108:Polymers / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; D011108:Polymers; D013662:Tea; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate