A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1.
A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1.
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DOI：
10.1371/journal.pone.0001153
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发表时间：
2007-11-07
期刊：
影响因子：
3.7
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Li W;Ashok M;Li J;Yang H;Sama AE;Wang H
脓毒症的发病机制部分由细菌内毒素介导，内毒素刺激巨噬细胞/单核细胞依次释放早期（如肿瘤坏死因子、白细胞介素 - 1和干扰素 - γ）和晚期（如高迁移率族蛋白B1）促炎细胞因子。我们最近发现高迁移率族蛋白B1是致死性脓毒症的一种晚期介质，这促使人们研究开发新的实验性治疗方法。我们之前报道过，由茶树叶子泡制的绿茶能有效抑制内毒素诱导的高迁移率族蛋白B1释放。
在此我们证明，其主要成分（ - ） - 表没食子儿茶素 - 3 - 没食子酸酯（EGCG），而非儿茶素或没食子酸乙酯，能在巨噬细胞/单核细胞培养中剂量依赖性地抑制高迁移率族蛋白B1释放，即使在脂多糖刺激后2 - 6小时给予也是如此。腹腔注射EGCG可保护小鼠免受致死性内毒素血症的侵害，并且即使在盲肠结扎和穿孔24小时后给予第一剂，也能使小鼠从致死性脓毒症中获救。其治疗效果部分归因于：1）减轻致死性脓毒症的促炎介质（如高迁移率族蛋白B1）和替代标志物（如白细胞介素 - 6和角质细胞趋化因子）的全身蓄积；2）通过阻止外源性高迁移率族蛋白B1在巨噬细胞表面聚集来抑制高迁移率族蛋白B1介导的炎症反应。
综上所述，这些数据表明了绿茶的主要成分EGCG预防致死性内毒素血症和脓毒症的一种新机制。
The pathogenesis of sepsis is mediated in part by bacterial endotoxin, which stimulates macrophages/monocytes to sequentially release early (e.g., TNF, IL-1, and IFN-γ) and late (e.g., HMGB1) pro-inflammatory cytokines. Our recent discovery of HMGB1 as a late mediator of lethal sepsis has prompted investigation for development of new experimental therapeutics. We previously reported that green tea brewed from the leaves of the plant Camellia sinensis is effective in inhibiting endotoxin-induced HMGB1 release. Here we demonstrate that its major component, (-)-epigallocatechin-3-gallate (EGCG), but not catechin or ethyl gallate, dose-dependently abrogated HMGB1 release in macrophage/monocyte cultures, even when given 2–6 hours post LPS stimulation. Intraperitoneal administration of EGCG protected mice against lethal endotoxemia, and rescued mice from lethal sepsis even when the first dose was given 24 hours after cecal ligation and puncture. The therapeutic effects were partly attributable to: 1) attenuation of systemic accumulation of proinflammatory mediator (e.g., HMGB1) and surrogate marker (e.g., IL-6 and KC) of lethal sepsis; and 2) suppression of HMGB1-mediated inflammatory responses by preventing clustering of exogenous HMGB1 on macrophage cell surface. Taken together, these data suggest a novel mechanism by which the major green tea component, EGCG, protects against lethal endotoxemia and sepsis.
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