在一種鼠類模型中綠茶多酚可以阻斷內毒素誘發之腫瘤壞死因子之生成及致死性

Green Tea Polyphenols Block Endotoxin-Induced Tumor Necrosis Factor-Production and Lethality in a Murine Model

劉紹毅 ； Fa-Jun Yang ； Willem J. S. DE Villiers ； Craig J. McClain ； Gary W. Varilek

《中華民國血液淨化醫學會雜誌》 14卷3-4期 (2009/12) Pp. 77-78

https://doi.org/10.30024/JFBPS.200912.0016

摘要

綠茶多酚(green tea polyphenols, GTP)爲強力抗氧化物。它們其有抗癌與抗發炎作用。然而，其作用機轉未明。在炎症反應中，腫瘤壞死因子－α(tumor necrosis factor-α, TNF-α)扮演著一種關鍵性角色。NFkB是一個氧化壓力－敏感性細胞核轉錄因子，它控制著許多個基因表現，包括TNF-α基因。我們假設綠茶多酚可透過其抗氧化作用特性，來調節NFkB之活化作用以控制TNF-α之基因表現。在巨噬細胞象之RAW264.7中，EGCG這個主要之綠茶多酚，在劑量－依賴性作用方式下（在劑量為100mmol/L時，抑制50%），可以減少由脂多醣(Lipopolysaccharide, LPS)所誘發之TNF-α。EGCG也可抑制LPS所誘發的TNF-α mRAN表現及在RAW264.7細胞核內NFkB之鍵結活性（在100mmol/L劑量下，抑制30~40%）。同樣地，在被誘發之小鼠腹腔巨噬細胞中，EGCG可將LPS-誘發之TNF-α生成作用抑制。在雄性BALB/c小鼠中，在利用腹腔腔內注射40mg/kg LPS之前2個小時，先以口灌食綠茶多酚，結果在劑量－反應作用方式中，綠茶多酚可使血清中LPS-誘發之TNF-α生成作用減少。在劑量為0.5gm/kg之綠茶多酚給予下，血清中之TNF-α比控制組減少80%。再者，給0.5gm/kg體重之綠茶多酚予雄性之BALB/c小鼠時，可以完全抑制LPS-誘發之死亡。我們的結論是綠茶多酚的抗發炎作用機轉，至少有一部分是藉由綠茶多酚居間媒介對NFkB活化作用之阻斷因而使TNF-α基因表現向下調節而來，這些發現顯示出綠茶多酚對於各種不同之炎症作用過程，可提供有效之治療。

並列摘要

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 (TNF α) plays a pivotal role. NF-κB, an oxidative stress-sensitive nuclear transcription factor, controls the expression of many genes including the TNF α gene. We postulated that green tea polyphenols regulate TNF α gene expression by modulating NF-κ B activation through their antioxidant properties. In the macrophage cell line, RA W264.7, (-)-epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNF α production in a-dose dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNF α mRNA expression and nuclear NF-κB-inding activity in RA W264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNF α 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 α production in serum in a dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt, serum TNF α 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 α gene expression by blocking NF-κ B activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.

並列關鍵字

mice ； polyphenols ； tea ； endotoxin ； tumor necrosis factor