Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, Seoul, Korea.
Biotechnol J. 2010 Sep;5(9):950-60. doi: 10.1002/biot.201000068.
Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species. Oleuropein is also reported to have protective effects against non-alcoholic fatty liver disease (NAFLD) in vivo. In this study, gene expression profiling of hepatic tissues was examined, and transcription factors (TFs) with target genes that were modulated by oleuropein were identified to gain insights into the molecular mechanisms for the hepatoprotective action of this compound. C57BL/6N mice were fed either a high-fat diet (HFD) or 0.03% oleuropein-supplemented HFD for 10 weeks, after which their livers were subjected to oligo DNA microarray analysis. The oleuropein with which the HFD was supplemented reduced the hepatic mRNA level of the genes that encoded the key regulators of the hepatic fatty acid uptake and transport. In addition, the oleuropein reduced the expression of a number of hepatic genes involved in the oxidative stress responses and detoxification of lipid peroxidation products and proinflammatory cytokine genes. The (putative) candidate TFs that bound to the promoters of the genes regulated at least threefold (both up and down) by oleuropein were implicated in the lipogenesis, inflammation, insulin resistance, fibrosis, and cell proliferation and differentiation, which implies that the mechanisms that underlie the beneficial effects of oleuropein on NAFLD may be multifactorial.
橄榄叶中的活性成分橄榄苦苷具有多种与清除活性氧物种相关的药理活性。橄榄苦苷还被报道具有预防非酒精性脂肪性肝病（NAFLD）的体内保护作用。在这项研究中，检查了肝组织的基因表达谱，并确定了被橄榄苦苷调节的靶基因的转录因子（TFs），以深入了解该化合物的肝保护作用的分子机制。用高脂肪饮食（HFD）或 0.03%添加橄榄苦苷的 HFD 喂养 C57BL/6N 小鼠 10 周，然后对其肝脏进行寡 DNA 微阵列分析。用 HFD 补充的橄榄苦苷降低了编码肝脏脂肪酸摄取和转运关键调节剂的基因的肝 mRNA 水平。此外，橄榄苦苷还降低了参与氧化应激反应和脂质过氧化产物解毒以及促炎细胞因子基因表达的许多肝基因的表达。与至少三倍（上调和下调）受橄榄苦苷调节的基因启动子结合的（假定）候选 TF 参与了脂肪生成、炎症、胰岛素抵抗、纤维化以及细胞增殖和分化，这意味着橄榄苦苷对 NAFLD 的有益作用的机制可能是多因素的。
