Frontier Laboratories for Value Creation, SAPPORO HOLDINGS LTD., 10 Okatome, Yaizu, Shizuoka 425-0013, Japan.
Division of Neurology, Anti-Aging, and Vascular Medicine, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
J Nutr Biochem. 2017 Sep;47:29-34. doi: 10.1016/j.jnutbio.2017.04.011. Epub 2017 Apr 22.
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 [H]-cholesterol-labeled macrophages. Ex vivo experiments were then employed to investigate the detailed mechanism by which xanthohumol enhanced RCT. Cholesterol efflux capacity from macrophages was 1.5-fold higher in xanthohumol-fed hamsters compared with the control group. In addition, protein expression and lecithin-cholesterol acyltransferase activity in the HDL fraction were significantly higher in xanthohumol-fed hamsters compared with the control, suggesting that xanthohumol promoted HDL maturation. Hepatic transcript analysis revealed that xanthohumol increased mRNA expression of abcg8 and cyp7a1. In addition, protein expressions of liver X receptor α and bile pump export protein were increased in the liver by xanthohumol administration when compared with the control, implying that it stimulated bile acid synthesis and cholesterol excretion to feces. In conclusion, our data demonstrate that xanthohumol improves RCT in vivo through cholesterol efflux from macrophages and excretion to feces, leading to antiatherosclerosis effects. It remains to be elucidated whether enhancement of RCT by xanthohumol could prove valuable in humans.
黄腐酚是一种来自啤酒花（Humulus lupulus L.）的重要类异戊二烯类黄酮，据报道其可升高高密度脂蛋白（HDL）胆固醇水平，具有抗动脉粥样硬化作用。然而，黄腐酚是否能促进胆固醇逆转运（RCT），即 HDL 的最重要抗动脉粥样硬化特性，目前尚不清楚。因此，我们采用 CETP 表达的仓鼠模型，研究了黄腐酚对巨噬细胞向粪便的 RCT 的影响。体内 RCT 实验表明，黄腐酚可显著增加腹腔内注射 [H]-胆固醇标记的巨噬细胞来源示踪剂在粪便中的出现。随后进行了离体实验，以研究黄腐酚增强 RCT 的详细机制。与对照组相比，黄腐酚喂养的仓鼠的巨噬细胞胆固醇流出能力高 1.5 倍。此外，黄腐酚喂养的仓鼠的 HDL 部分的蛋白表达和卵磷脂-胆固醇酰基转移酶活性明显高于对照组，提示黄腐酚促进了 HDL 的成熟。肝转录分析显示，黄腐酚增加了 abcg8 和 cyp7a1 的 mRNA 表达。此外，与对照组相比，黄腐酚给药后肝脏中肝 X 受体α和胆汁泵输出蛋白的蛋白表达增加，表明其刺激了胆汁酸合成和胆固醇向粪便的排泄。总之，我们的数据表明，黄腐酚通过巨噬细胞胆固醇外流和向粪便排泄来改善体内的 RCT，从而产生抗动脉粥样硬化作用。黄腐酚是否能增强 RCT 对人类是否有价值，还有待进一步阐明。
