Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: Molecular mechanisms and structure-activity relationship
Green tea proanthocyanidins inhibit cyclooxygenase-2 expression in LPS-activated mouse macrophages: Molecular mechanisms and structure-activity relationship
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DOI：
10.1016/j.abb.2007.01.009
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发表时间：
2007-04-01
影响因子：
3.9
通讯作者：
Sakata, Yusuke
中科院分区：
文献类型：
--
作者：
Hou, De-Xing;Masuzaki, Satoko;Sakata, Yusuke
在脂多糖 (LPS) 激活的鼠巨噬细胞 RAW264 细胞中研究了绿茶原花青素对环氧合酶 2 (COX-2) 表达和前列腺素 E-2 (PGE(2)) 释放的抑制作用。 Prodelphinidin B2 3,3' di-O-gallate (PDGG) 在 mRNA 和蛋白质水平上引起 COX-2 的剂量依赖性抑制，并伴随 PGE(2) 的释放。分子证据表明，PDGG 抑制 I kappa-B 的降解、p65 和 CCAAT/增强子结合蛋白 (C/EBP)delta 的核转位以及 c-Jun 的磷酸化，但不抑制调节 COX-2 表达的 CRE 结合蛋白 (CREB)。此外，PDGG 抑制丝裂原激活蛋白激酶 (MAPK) 的激活，包括 c-Jun NH2 末端激酶 (JNK)、细胞外信号调节激酶 (ERK) 和 p38 激酶。结果表明，PDGG 通过阻断 MAPK 介导的核因子 kappa B (NF-kappa B)、激活蛋白 1 (AP-1) 和 C/EBP δ 的激活来抑制 COX-2 表达。此外，使用五种原花青素进行结构-活性关系的研究表明，原花青素的没食子酰基部分对其抑制作用似乎很重要。因此，我们的研究结果提供了第一个分子基础，即具有没食子酰基部分的绿茶原花青素可能通过阻断 MAPK 介导的 COX-2 表达而具有抗炎特性。 (c) 2007 Elsevier Inc. 保留所有权利。
The inhibitory effects of green tea proanthocyanidins on cyclooxygenase-2 (COX-2) expression and prostaglandin E-2 (PGE(2)) release were investigated in lipopolysaccharide (LPS)-activated murine macrophage RAW264 cells. Prodelphinidin B2 3,3' di-O-gallate (PDGG) caused a dose-dependent inhibition of COX-2 at both mRNA and protein levels with the attendant release of PGE(2). Molecular evidence revealed that PDGG inhibited the degradation of I kappa-B, nuclear translocation of p65 and CCAAT/enhancer-binding protein (C/EBP)delta, and phosphorylation of c-Jun, but not CRE-binding protein (CREB), which regulate COX-2 expression. Moreover, PDGG suppressed the activations of mitogen-activated protein kinase (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 kinase. The results demonstrated that PDGG suppressed COX-2 expression via blocking MAPK-mediated activation of nuclear factor-kappa B (NF-kappa B), activator protein-1 (AP-1) and C/EBP delta. Furthermore, studies on structure-activity relationship using five kinds of proanthocyanidins revealed that the galloyl moiety of proanthocyanidins appeared important to their inhibitory actions. Thus, our findings provide the first molecular basis that green tea proanthocyanidins with the galloyl moiety might have anti-inflammatory properties through blocking MAPK-mediated COX-2 expression. (c) 2007 Elsevier Inc. All rights reserved.