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