xanthohumol and Atherosclerosis

Xanthohumol, a prominent prenyl flavonoid from the hop plant (Humulus lupulus L.), is suggested to be antiatherogenic since it reportedly increases high-density lipoprotein (HDL) cholesterol levels. It is not clear whether xanthohumol promotes reverse cholesterol transport (RCT), the most important antiatherogenic property of HDL; therefore, we investigated the effects of xanthohumol on macrophage-to-feces RCT using a hamster model as a CETP-expressing species. In vivo RCT experiments showed that xanthohumol significantly increased fecal appearance of the tracer derived from intraperitoneally injected [

Topics: Animals; Anticholesteremic Agents; Atherosclerosis; ATP Binding Cassette Transporter, Subfamily G, Member 8; Biological Transport; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol Ester Transfer Proteins; Diet, High-Fat; Dietary Supplements; Feces; Flavonoids; Gastrointestinal Agents; Gene Expression Regulation, Developmental; Hypercholesterolemia; Intestinal Elimination; Lipoproteins, HDL; Liver; Macrophages; Male; Mesocricetus; Phosphatidylcholine-Sterol O-Acyltransferase; Propiophenones

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

Topics: Animals; Aorta, Thoracic; Apolipoproteins E; Atherosclerosis; Blotting, Western; Cholesterol; Cholesterol Ester Transfer Proteins; Diet, Atherogenic; Electrophoresis; Flavonoids; Mice; Mice, Inbred C57BL; Mice, Transgenic; Propiophenones; Real-Time Polymerase Chain Reaction; Transition Temperature