Xanthohumol Prevents Atherosclerosis by Reducing Arterial Cholesterol Content via CETP and Apolipoprotein E in CETP-Transgenic Mice

BackgroundXanthohumol 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 FindingsTwo 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 (%) (Pvia apoE-rich HDL resulting from CETP inhibition. ConclusionsOur results suggest xanthohumol prevents cholesterol accumulation in atherogenic regions by HDL-C metabolism via CETP inhibition leading to apoE enhancement.

背景：黄腐醇（Xanthohumol）可抑制胆固醇酯转移蛋白（cholesteryl ester transfer protein, CETP），因此被认为是一种强效抗动脉粥样硬化制剂。本研究中，我们提出假说：黄腐醇在活体水平可抑制动脉粥样硬化，并采用胆固醇酯转移蛋白转基因小鼠（CETP-Tg小鼠）评估黄腐醇作为功能制剂的效果。

材料与方法/主要研究结果：选取两种小鼠品系：CETP-Tg小鼠与C57BL/6N野生型小鼠，使其自由进食含或不含0.05%（质量分数）黄腐醇的高胆固醇饲料，干预周期为18周。在CETP-Tg小鼠中，与未添加黄腐醇的对照组相比，黄腐醇可显著降低主动脉弓处的胆固醇蓄积水平，并升高高密度脂蛋白胆固醇（HDL cholesterol, HDL-C）含量；而黄腐醇对野生型小鼠无显著影响。与对照组相比，CETP-Tg小鼠在补充黄腐醇后，其CETP活性显著降低，且该活性与HDL-C水平呈显著负相关（P<0.05，斯皮尔曼相关性分析）。此外，HDL-C水平的升高由CETP抑制所产生的富含载脂蛋白E（apoE）的HDL颗粒所介导。

结论：本研究结果表明，黄腐醇可通过抑制CETP增强载脂蛋白E介导的高密度脂蛋白胆固醇代谢，从而减少动脉粥样硬化易发区域的胆固醇蓄积。