title: Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE-deficient mice.
abstract: METHODS
  Xanthohumol (XN), a prenylated antioxidative and anti-inflammatory chalcone from hops, exhibits positive effects on lipid and glucose metabolism. Based on its favorable biological properties, we investigated whether XN attenuates atherosclerosis in western-type diet-fed apolipoprotein-E-deficient (ApoE⁻/⁻) mice.
  
  
  RESULTS
  XN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic triglyceride and cholesterol content, activation of AMP-activated protein kinase, phosphorylation and inactivation of acetyl-CoA carboxylase, and reduced expression levels of mature sterol regulatory element-binding protein (SREBP)-2 and SREBP-1c mRNA indicate reduced lipogenesis in the liver of XN-fed ApoE⁻/⁻ mice. Concomitant induction of hepatic mRNA expression of carnitine palmitoyltransferase-1a in ApoE⁻/⁻ mice-administered XN suggests increased fatty acid beta-oxidation. Fecal cholesterol concentrations were also markedly increased in XN-fed ApoE⁻/⁻ mice compared with mice fed western-type diet alone.
  
  
  CONCLUSIONS
  The atheroprotective effects of XN might be attributed to combined beneficial effects on plasma cholesterol and monocyte chemoattractant protein 1 concentrations and hepatic lipid metabolism via activation of AMP-activated protein kinase.
authors: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria.
authors: Prakash
authors: P
authors: Doddapattar
authors: Branislav
authors: B
authors: Radović
authors: Jay V
authors: JV
authors: Patankar
authors: Sascha
authors: S
authors: Obrowsky
authors: Katharina
authors: K
authors: Jandl
authors: Christoph
authors: C
authors: Nusshold
authors: Dagmar
authors: D
authors: Kolb
authors: Nemanja
authors: N
authors: Vujić
authors: Lalit
authors: L
authors: Doshi
authors: Prakash G
authors: PG
authors: Chandak
authors: Madeleine
authors: M
authors: Goeritzer
authors: Helmut
authors: H
authors: Ahammer
authors: Gerald
authors: G
authors: Hoefler
authors: Wolfgang
authors: W
authors: Sattler
authors: Dagmar
authors: D
authors: Kratky
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D005234:Fatty Liver / Q000188:drug therapy*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D058226:Plaque, Atherosclerotic / Q000188:drug therapy*; D011427:Propiophenones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005419:Flavonoids; D011427:Propiophenones; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; D002784:Cholesterol; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C104536:xanthohumol
keywords: AMPK signaling; Atherosclerosis; Inflammation; Lipid metabolism; Xanthohumol
references: Diabetes. 2005 Jan;54(1):63-8
references: 15616011
references: J Lipid Res. 2012 Mar;53(3):446-455
references: 22190590
references: Arterioscler Thromb Vasc Biol. 2008 Dec;28(12):2255-7
references: 18802013
references: Cell. 1992 Oct 16;71(2):343-53
references: 1423598
references: Exp Mol Pathol. 2013 Feb;94(1):10-6
references: 22634733
references: Apoptosis. 2007 Nov;12(11):1953-63
references: 17874298
references: PLoS One. 2012;7(11):e49415
references: 23166663
references: Biochem J. 1970 Jul;118(3):519-30
references: 5472179
references: Cancer. 2007 Nov 1;110(9):2007-11
references: 17823911
references: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8552-7
references: 16717184
references: J Biol Chem. 2003 Jul 11;278(28):25448-53
references: 12704191
references: Annu Rev Biochem. 1983;52:537-79
references: 6137188
references: Mol Nutr Food Res. 2005 Sep;49(9):861-7
references: 16092070
references: EMBO J. 1990 Aug;9(8):2439-46
references: 2369897
references: Biochim Biophys Acta. 2011 Dec;1811(12):1011-20
references: 21924378
references: Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9261-5
references: 8415689
references: Biochem Biophys Res Commun. 2012 Mar 9;419(2):200-5
references: 22330806
references: J Clin Invest. 1969 Jun;48(6):982-91
references: 5771198
references: Obesity (Silver Spring). 2008 Jun;16(6):1232-8
references: 18369342
references: J Chromatogr Sci. 2004 Aug;42(7):378-82
references: 15355578
references: In Vivo. 2005 Jan-Feb;19(1):103-7
references: 15796161
references: Nature. 1998 Aug 27;394(6696):894-7
references: 9732872
references: Cell Metab. 2005 Feb;1(2):121-31
references: 16054053
references: Int Immunopharmacol. 2008 Apr;8(4):567-73
references: 18328448
references: J Agric Food Chem. 2009 Aug 26;57(16):7274-81
references: 19634869
references: FASEB J. 2006 Mar;20(3):527-9
references: 16403733
references: Biochem J. 1990 Jun 15;268(3):685-91
references: 2363705
references: Biochem J. 1999 Mar 15;338 ( Pt 3):783-91
references: 10051453
references: Am J Physiol. 1999 Jul;277(1):E1-10
references: 10409121
references: J Cell Biochem. 2008 Aug 1;104(5):1699-707
references: 18348194
references: J Nutr. 2004 Jun;134(6):1340-6
references: 15173394
references: J Clin Invest. 2004 Jul;114(2):147-52
references: 15254578
references: Biochem Biophys Res Commun. 2005 Oct 28;336(3):754-61
references: 16140264
references: N Engl J Med. 1999 Jan 14;340(2):115-26
references: 9887164
references: Int Immunopharmacol. 2010 May;10(5):556-61
references: 20144742
references: Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E955-64
references: 19208854
references: Phytochemistry. 2013 Jul;91:236-41
references: 22640929
references: J Biol Chem. 2005 Sep 16;280(37):32081-9
references: 16027121
references: Anticancer Res. 2010 Sep;30(9):3333-9
references: 20944105
references: J Am Soc Nephrol. 2011 Oct;22(10):1846-55
references: 21921143
references: Biochem Biophys Res Commun. 1991 Dec 31;181(3):1486-92
references: 1684896
references: Food Chem Toxicol. 2010 Jul;48(7):1890-7
references: 20427021
references: Mol Nutr Food Res. 2010 Oct;54(10):1405-13
references: 20397197
references: Immunopharmacol Immunotoxicol. 2009;31(3):477-84
references: 19555200
references: Cell Metab. 2011 Apr 6;13(4):376-388
references: 21459323
references: Sci Am. 1984 Nov;251(5):58-66
references: 6390676
references: Nat Immunol. 2011 Mar;12(3):204-12
references: 21321594
references: Mol Nutr Food Res. 2012 Mar;56(3):466-74
references: 22147307
references: J Clin Invest. 1999 Mar;103(6):773-8
references: 10079097
references: Eur J Biochem. 1988 Aug 1;175(2):331-8
references: 2900138