Hepatoprotective effect of oleuropein in mice: Mechanisms uncovered by gene expression profiling

Biotechnology Journal - Tập 5 Số 9 - Trang 950-960 - 2010
Yunjung Kim1, Youngshim Choi2, Taesun Park1
1Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, Seoul, Korea
2, Yonsei University

Tóm tắt

AbstractOleuropein, 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.

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Tài liệu tham khảo

10.1093/jn/136.10.2512

10.1038/sj.ijo.0802926

10.1158/0008-5472.CAN-07-2464

10.1158/0008-5472.CAN-05-3918

10.1093/jn/136.8.2213

10.1093/jn/135.6.1475

10.1016/j.bbrc.2005.06.161

10.1016/j.lfs.2005.07.029

10.3177/jnsv.54.363

10.3109/00313020903434389

10.3945/jn.109.117812

10.1016/j.nutres.2008.03.015

10.1016/S0021-9258(18)64849-5

10.1038/75556

10.1146/annurev.nu.14.070194.002015

10.1016/j.plipres.2008.08.001

10.1152/ajpgi.2001.281.5.G1135

10.1172/JCI200422422

10.2337/db07-0907

10.1074/jbc.M100052200

10.1053/j.gastro.2007.11.037

10.1097/01.mol.0000180166.08196.07

10.1073/pnas.051619898

10.1074/jbc.M205079200

10.1016/j.gene.2004.06.015

10.1002/biot.200900228

10.1006/bbrc.1998.8735

10.1016/0021-9150(95)05546-9

Bohmann D., 1990, Transcription factor phosphorylation: A link between signal transduction and the regulation of gene expression., Cancer Cells, 2, 337

10.1007/978-1-59745-566-4_9

10.1074/jbc.M300043200

10.1210/me.2004-0213

10.1093/jn/135.11.2503

10.1194/jlr.M300235-JLR200

10.1002/hep.21713

10.1002/hep.23469

10.1016/j.cmet.2009.04.001

10.1128/MCB.21.4.1393-1403.2001

10.1016/j.bbrc.2007.01.008

10.1016/j.cmet.2006.11.008

10.1038/nrm2335

10.1093/emboj/cdg438

10.1016/j.jamcollsurg.2006.01.007

10.1074/jbc.M606923200

10.1038/nrm2066

10.1038/35093131

10.1677/JME-08-0004

10.1074/jbc.M707390200

10.4161/cc.5.2.2311

10.1016/j.stem.2008.06.002

10.1146/annurev.cellbio.23.090506.123438

10.1210/en.2008-0361

10.1073/pnas.90.4.1440

10.2337/db09-1541

10.2337/diab.46.9.1526

10.1021/jf901280r

10.1091/mbc.E04-05-0439

10.1126/science.1151363

10.1002/mnfr.200900111

10.1021/jf8026217

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Biotechnology Journal

Tập 5 Số 9

950-960

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