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Manuscript received 4 June 1998. Initial reviews completed 9 July 1998. Revision accepted 18 August 1998.
,
, and
* Graduate Program in Nutritional Sciences, Department of Internal Medicine, Department of Internal Medicine and Graduate Programs in Toxicology and Nutritional Sciences, and ** Department of Internal Medicine, University of Kentucky and Veterans Administration Medical Center, Lexington, KY 40536
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-
(TNF) plays a pivotal role. NF-KB, an oxidative stress -sensitive nuclear transcription factor, controls the expression of many genes including the TNF gene. We postulated that green tea polyphenols regulate TNF 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 TNF production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNF mRNA expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNF 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 production in serum in a dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt, serum TNF 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 gene expression by blocking NF-KB activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.
The Journal of Nutrition Vol. 128 No. 12 December 1998,
pp. 2334-2340
Copyright ©1998 by the American Society for Nutritional Sciences
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