Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats.
Luteolin and quercetin affect the cholesterol absorption mediated by epithelial cholesterol transporter niemann-pick c1-like 1 in caco-2 cells and rats.
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DOI：
10.1371/journal.pone.0097901
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kobayashi S
中科院分区：
文献类型：
--
作者：
Nekohashi M;Ogawa M;Ogihara T;Nakazawa K;Kato H;Misaka T;Abe K;Kobayashi S
NPC 1 L1介导胆固醇的吸收，依折麦布是一种有效的NPC 1 L1抑制剂，适用于高胆固醇血症的药物治疗。流行病学研究表明，多酚的消费与动脉粥样硬化的风险降低有关，因为它们具有抗氧化作用。这种活性很难归因于抗氧化活性，我们假设多酚抑制胆固醇的肠道转运。我们阐明了肠道胆固醇吸收的动力学参数，筛选了几种多酚，他们的能力，特异性地抑制肠道胆固醇吸收，并确定所选黄酮类化合物在体外和体内的抑制作用。Caco-2细胞对胆固醇的摄取呈浓度依赖性，且呈双相饱和过程。这表明涉及主动-被动运输，即，NPC1L1。Caco-2细胞摄取胆固醇的参数如下：Jmax、Kt和Kd分别为6.89±2.96、19.03±11.58 µM和0.11±0.02 pmol/min/mg蛋白。木犀草素和槲皮素抑制表达NPC 1 L1的Caco-2细胞和人胚肾293 T细胞的胆固醇吸收。当预孵育Caco-2细胞与木犀草素和槲皮素的测定前，胆固醇摄取显着降低。这些黄酮类化合物的抑制作用可维持长达120 min。抑制水平和不可逆作用与依折麦布相似。血清胆固醇水平显着降低更多的大鼠喂养胆固醇和木犀草素（或槲皮素），比那些观察到的胆固醇喂养组。由于槲皮素诱导Caco-2细胞中NPC 1 L1 mRNA水平显著降低，因此体内抑制作用可能是由于NPC 1 L1的表达。这些结果表明，木犀草素和槲皮素通过特异性抑制由NPC 1 L1介导的肠胆固醇吸收来降低高血胆固醇水平。
Niemann–Pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis due to their antioxidant effect. This activity can hardly be attributable to the antioxidant activity only, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption, screened several polyphenols for their ability to specifically inhibit intestinal cholesterol absorption, and determined the inhibitory effects of selected flavonoids in vitro and in vivo. The concentration-dependent uptake of cholesterol by Caco-2 cells obeyed a monophasic saturation process. This indicates the involvement of an active-passive transport, i.e., NPC1L1. Parameters of cholesterol uptake by Caco-2 cells were as follows: J max, K t, and K d were 6.89±2.96 19.03±11.58 µM, and 0.11±0.02 pmol/min/mg protein, respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake significantly decreased. The inhibitory effects of these flavonoids were maintained for up to 120 min. The level of inhibition and irreversible effects were similar to that of ezetimibe. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. As quercetin induced a significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo inhibitory effect may be due to the expression of NPC1L1. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.
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DOI：
10.1016/j.jand.2013.09.021
发表时间：
2014-02-01
影响因子：
4.8
作者：
Gadgil, Meghana D.;Anderson, Cheryl A. M.;Kanaya, Alka M.
通讯作者：
Kanaya, Alka M.
胆固醇吸收抑制剂依折麦布通过阻断甾醇诱导的 NPC1L1 内化发挥作用
影响因子：
29
作者：
Ge, Liang;Wang, Jing;Song, Bao-Liang
通讯作者：
Song, Bao-Liang
DOI：
10.1073/pnas.1014434108
发表时间：
2011-01-11
影响因子：
11.1
作者：
Ge, Liang;Qi, Wei;Song, Bao-Liang
通讯作者：
Song, Bao-Liang
影响因子：
4.5
作者：
Feng D;Ohlsson L;Duan RD
通讯作者：
Duan RD
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP