College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Food Chem Toxicol. 2010 Feb;48(2):579-86. doi: 10.1016/j.fct.2009.11.035. Epub 2009 Nov 14.
Dihydro-N-caffeoyltyramine (DHCT), a novel phenolic amide isolated from the root bark of Lycium chinense Miller, has potent antioxidative activity and anti-fungal effects. In the present study, we investigated the effects of DHCT on phorbol 12-myristate 13-acetate (PMA)-induced pro-inflammatory protein cyclooxygenase (COX-2) expression in macrophages. Treatment with DHCT suppressed PMA-mediated induction of COX-2 mRNA and protein. PMA-inducible production of PGE2 was inhibited by DHCT in a dose-dependent manner. Transient transfections and electrophoretic mobility shift assays indicated that the inhibitory effects of DHCT were mediated via CCAAT/enhancer-binding protein (C/EBP) and activator protein 1 (AP-1). DHCT reduced PMA-induced C/EBPbeta protein expression and c-jun/c-fos gene and protein expression. Furthermore, DHCT significantly inhibited PMA-induced activation of the mitogen activated protein (MAP) kinases (ERK and JNK). Thus, DHCT is an effective agent to attenuate COX-2 production mediated by the transcription factors C/EBP and AP-1, and these results enhance our understanding of the anti-inflammatory and anti-cancer properties by DHCT.
二氢-N-咖啡酰酪胺（DHCT）是从中华枸杞根皮中分离得到的一种新型酚酰胺，具有很强的抗氧化活性和抗真菌作用。在本研究中，我们研究了 DHCT 对佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的巨噬细胞炎症蛋白环氧化酶（COX-2）表达的影响。DHCT 处理抑制了 PMA 介导的 COX-2 mRNA 和蛋白的诱导。DHCT 以剂量依赖的方式抑制 PMA 诱导的 PGE2 产生。瞬时转染和电泳迁移率变动分析表明，DHCT 的抑制作用是通过 CCAAT/增强子结合蛋白（C/EBP）和激活蛋白 1（AP-1）介导的。DHCT 降低了 PMA 诱导的 C/EBPβ蛋白表达以及 c-jun/c-fos 基因和蛋白表达。此外，DHCT 显著抑制了 PMA 诱导的丝裂原激活蛋白（MAP）激酶（ERK 和 JNK）的激活。因此，DHCT 是一种有效的减轻转录因子 C/EBP 和 AP-1 介导的 COX-2 产生的药物，这些结果增强了我们对 DHCT 的抗炎和抗癌特性的理解。
