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-α(TNFα) plays a pivotal role. NF-κB, an oxidative stress -sensitive nuclear transcription factor, controls the expression of many genes including the TNFα gene. We postulated that green tea polyphenols regulate TNFα gene expression by modulating NF-κB activation through their antioxidant properties. In the macrophage cell line, RAW264.7, (-)-epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNFα production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFα mRNA expression and nuclear NF-κB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFα 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 TNFα production in serum in a dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt, serum TNFα 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 TNFα gene expression by blocking NF-κB activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.