Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model
Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model
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DOI：
10.1093/jn/128.12.2334
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发表时间：
1998-12-01
影响因子：
4.2
通讯作者：
Varilek, GW
中科院分区：
文献类型：
--
作者：
Yang, FJ;de Villers, WJS;Varilek, GW
绿色茶多酚是有效的抗氧化剂。它们具有抗癌和抗炎作用，但其作用机制尚不清楚。在炎症中，肿瘤坏死因子-α（TNF α）起着关键作用。NF-κ B是一种氧化应激敏感的核转录因子，控制包括TNF α基因在内的许多基因的表达。我们推测，绿色茶多酚通过其抗氧化特性调节NF-κ B B活化来调节TNF α基因表达。在巨噬细胞系中，RAW 264.7，（-）-表没食子儿茶素没食子酸酯（EGCG），主要的绿色茶多酚，以剂量依赖性方式减少脂多糖（LPS）诱导的TNF α产生（100 mmol/L时50%抑制），EGCG还抑制LPS诱导的RAW264.7细胞TNF α mRNA表达和核NF-κ B结合活性（100 mmol/L时抑制30-40%）。类似地，EGCG抑制LPS诱导的小鼠腹腔巨噬细胞中TNF α的产生。在雄性BALB/c小鼠中，绿色茶多酚（在腹腔注射40 mg LPS/kg体重前2 h经口灌胃给药）以剂量响应方式降低LPS诱导的血清TNF α产生。在0.5 g绿色茶多酚/kg体重的剂量下，血清TNF α降低了对照组的80%。此外，0.5 g绿色茶多酚/kg体重完全抑制LPS诱导的雄性BALB/c小鼠的致死率。我们的结论是，绿色茶多酚的抗炎机制介导的至少部分通过下调TNF α基因的表达，通过阻断NF-κ B激活。这些发现表明，绿色茶多酚可能是有效的治疗各种炎症过程。
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.