Xanthohumol prevents atherosclerosis by reducing arterial cholesterol content via CETP and apolipoprotein E in CETP-transgenic mice

PLoS One. 2012;7(11):e49415. doi: 10.1371/journal.pone.0049415. Epub 2012 Nov 16.

Abstract

Background: Xanthohumol is expected to be a potent anti-atherosclerotic agent due to its inhibition of cholesteryl ester transfer protein (CETP). In this study, we hypothesized that xanthohumol prevents atherosclerosis in vivo and used CETP-transgenic mice (CETP-Tg mice) to evaluate xanthohumol as a functional agent.

Methodology/principal findings: Two strains of mice, CETP-Tg and C57BL/6N (wild-type), were fed a high cholesterol diet with or without 0.05% (w/w) xanthohumol ad libitum for 18 weeks. In CETP-Tg mice, xanthohumol significantly decreased accumulated cholesterol in the aortic arch and increased HDL cholesterol (HDL-C) when compared to the control group (without xanthohumol). Xanthohumol had no significant effect in wild-type mice. CETP activity was significantly decreased after xanthohumol addition in CETP-Tg mice compared with the control group and it inversely correlated with HDL-C (%) (P<0.05). Furthermore, apolipoprotein E (apoE) was enriched in serum and the HDL-fraction in CETP-Tg mice after xanthohumol addition, suggesting that xanthohumol ameliorates reverse cholesterol transport via apoE-rich HDL resulting from CETP inhibition.

Conclusions: Our results suggest xanthohumol prevents cholesterol accumulation in atherogenic regions by HDL-C metabolism via CETP inhibition leading to apoE enhancement.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / metabolism
  • Apolipoproteins E / metabolism*
  • Atherosclerosis / prevention & control*
  • Blotting, Western
  • Cholesterol / metabolism*
  • Cholesterol Ester Transfer Proteins / genetics
  • Cholesterol Ester Transfer Proteins / metabolism*
  • Diet, Atherogenic
  • Electrophoresis
  • Flavonoids / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Propiophenones / pharmacology*
  • Real-Time Polymerase Chain Reaction
  • Transition Temperature

Substances

  • Apolipoproteins E
  • Cholesterol Ester Transfer Proteins
  • Flavonoids
  • Propiophenones
  • Cholesterol
  • xanthohumol

Grant support

This research was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and also by Sapporo Biocluster "Bio-S", the Regional Innovation Cluster Program, the Ministry of Education, Culture, Sports, Science and Technology, Japan. No additional external funding received for this study.