A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration
A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration
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DOI：
10.3762/bjoc.10.300
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发表时间：
2014-12-02
影响因子：
2.7
通讯作者：
Sakamoto, Norihiro
中科院分区：
文献类型：
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作者：
Furune, Takahiro;Ikuta, Naoko;Sakamoto, Norihiro
背景：胆固醇与卵磷脂和胆汁盐形成胶束是肠道吸收脂质的关键过程。一些常用于降低体内脂质含量的膳食纤维被认为是通过与胆汁盐结合并降低脂质溶解度来抑制脂质吸收。其中，据报道α - 环糊精（α - CD）是降低血液胆固醇最有效的膳食纤维之一。然而，很难相信α - CD会直接去除胆固醇，因为它对胆固醇的亲和力非常低，而且其作用机制不如其他膳食纤维那么清楚。为了确定这一机制，我们研究了α - CD与卵磷脂和胆汁盐的相互作用（卵磷脂和胆汁盐是胆固醇在小肠中溶解的必需成分），以及α - CD对胆固醇胶束溶解度的影响。
结果：将α - CD加入到进食状态模拟肠液（FeSSIF）中，观察到有白色固体沉淀。分析数据表明，沉淀物是卵磷脂与α - CD的复合物，摩尔比为1 : 4或1 : 5。研究了胆固醇在FeSSIF和α - CD混合物中的胶束溶解度，发现由于添加α - CD导致卵磷脂沉淀，胆固醇胶束溶解度以剂量依赖的方式降低。此外，将其他几种水溶性膳食纤维分别加入到FeSSIF中，没有产生沉淀。
结论：本研究表明，α - CD通过与α - CD形成复合物使胆汁盐胶束中的卵磷脂沉淀，从而降低小肠腔内胆固醇的胶束溶解度。它还表明，添加α - CD对胆汁盐胶束的卵磷脂沉淀作用明显不同于添加其他水溶性膳食纤维。在FeSSIF中，添加α - CD时胆固醇胶束溶解度的降低最为显著。
Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, alpha-cyclodextrin (alpha-CD) is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that alpha-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of alpha-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of alpha-CD on micellar solubility of cholesterol.Results: alpha-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF), and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and alpha-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and alpha-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of alpha-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated.Conclusion: This study suggests that alpha-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with alpha-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by alpha-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with alpha-CD addition.