Lin Chun-Yu, Lee Chien-Hsing, Chang Yu-Wei, Wang Hui-Min, Chen Chung-Yi, Chen Yen-Hsu
Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 736, Taiwan.
Int J Mol Sci. 2014 Dec 9;15(12):22819-34. doi: 10.3390/ijms151222819.
Inflammation is a serious health issue worldwide that induces many diseases such as sepsis. There has been a vast search for potentially effective drugs to decrease mortality from sepsis. Pheophytin a is a chlorophyll-related compound derived from green tea. We found that pre-treatment with pheophytin a suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-1β in RAW 264.7 macrophages. NO synthase-2 (NOS2) and cyclooxygenase-2 (COX-2) expression levels were repressed by pre-treatment with pheophytin a at both the transcriptional and translational levels. Pheophytin a inhibited NOS2 promoter activity, but not its mRNA stability, through extracellular signal-regulated kinase (ERK1/2). This suppression was reversed by ERK1/2 inhibitor (U0126). Pheophytin a reduced signal transducers and activators of transcription 1 (STAT-1) activation, without an obvious influence on activator protein-1 (AP-1) and nuclear factor κB (NF-κB). These results suggest that pheophytin a functions by down-regulating the transcriptional levels of inflammatory mediators and blocking the ERK and STAT-1 pathways.
炎症是一个全球性的严重健康问题，可引发许多疾病，如败血症。人们一直在广泛寻找可能有效的药物以降低败血症的死亡率。脱镁叶绿素a是一种源自绿茶的叶绿素相关化合物。我们发现，用脱镁叶绿素a预处理可抑制RAW 264.7巨噬细胞中脂多糖（LPS）诱导的一氧化氮（NO）、前列腺素E2（PGE2）和白细胞介素-1β的产生。脱镁叶绿素a预处理在转录和翻译水平上均抑制了一氧化氮合酶-2（NOS2）和环氧化酶-2（COX-2）的表达水平。脱镁叶绿素a通过细胞外信号调节激酶（ERK1/2）抑制NOS2启动子活性，但不影响其mRNA稳定性。ERK1/2抑制剂（U0126）可逆转这种抑制作用。脱镁叶绿素a降低了信号转导和转录激活因子1（STAT-1）的激活，而对激活蛋白-1（AP-1）和核因子κB（NF-κB）没有明显影响。这些结果表明，脱镁叶绿素a通过下调炎症介质的转录水平并阻断ERK和STAT-1途径发挥作用。
