Xanthohumol ameliorates atherosclerotic plaque formation, hypercholesterolemia, and hepatic steatosis in ApoE-deficient mice.
SCOPE
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.


METHODS AND 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.


CONCLUSION
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.
['Doddapattar|Prakash|P|', 'Radović|Branislav|B|', 'Patankar|Jay V|JV|', 'Obrowsky|Sascha|S|', 'Jandl|Katharina|K|', 'Nusshold|Christoph|C|', 'Kolb|Dagmar|D|', 'Vujić|Nemanja|N|', 'Doshi|Lalit|L|', 'Chandak|Prakash G|PG|', 'Goeritzer|Madeleine|M|', 'Ahammer|Helmut|H|', 'Hoefler|Gerald|G|', 'Sattler|Wolfgang|W|', 'Kratky|Dagmar|D|']
D055372:AMP-Activated Protein Kinases D000103:Acetyl-CoA Carboxylase D000818:Animals D001057:Apolipoproteins E D002334:Carnitine O-Palmitoyltransferase D018932:Chemokine CCL2 D002784:Cholesterol D005234:Fatty Liver D005260:Female D005419:Flavonoids D006937:Hypercholesterolemia D050356:Lipid Metabolism D050155:Lipogenesis D008099:Liver D051379:Mice D010766:Phosphorylation D058226:Plaque, Atherosclerotic D011427:Propiophenones D012333:RNA, Messenger D051780:Sterol Regulatory Element Binding Protein 1 D051782:Sterol Regulatory Element Binding Protein 2 D014280:Triglycerides
Xanthohumol Atherosclerosis Lipid metabolism AMPK signaling Inflammation