Esterification of Quercetin Increases Its Transport Across Human Caco-2 Cells
Esterification of Quercetin Increases Its Transport Across Human Caco-2 Cells
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槲皮素的酯化增加了其在人 Caco-2 细胞中的转运
DOI：
10.1111/1750-3841.13366
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发表时间：
2016-07-01
影响因子：
3.9
通讯作者：
Deng, Ze-yuan
中科院分区：
文献类型：
--
作者：
Hu, Jiang-ning;Zou, Xian-guo;Deng, Ze-yuan
植物多酚在体外表现出有用的生化特性，但由于吸收过程中对首过效应的强烈抵抗，其生物利用度有限，限制了其在体内的临床应用。为了提高槲皮素(QU)的生物利用度，合成了QU(3，3，4，5，7-五羟基黄酮，TAQU)的酯类化合物，并用人Caco-2细胞研究了QU及其酯类化合物(TAQU)的油水分配系数及其转运机理。系统地研究了不同条件(不同浓度、不同时间、不同pH、不同温度、不同紧密连接、不同潜在转运体)下Qu和TaQu的转运特性。结果表明，对于5~50M范围内的AP-BL转运，Qu具有较低的渗透系数(2.82×10(-6)cm/S)，而Ap到BL的转运速率(5.23×10(-6)cm/S)显著大于Qu。Qu和TaQu的转运过程中未涉及细胞旁通路。Qu被主动转运吸收较少，而TaQu主要被被动扩散吸收。外排转运蛋白、P-糖蛋白、多药耐药蛋白参与了Qu的转运过程，但不参与TaQu的转运过程。这些结果表明，通过酯化提高Qu的亲脂性可以增加Qu在Caco-2细胞中的转运。实际应用合成了Qu的酯类衍生物(TAQu)以提高Qu的生物利用度，并用Caco-2细胞证明了其转运效率。结果表明，通过酯化来改善Qu的脂类可以增加其在Caco-2细胞中的转运。因此，本研究可能为改善亲水性化合物的肠道吸收提供一种有用的分子结构修饰策略。
Plant polyphenols showed useful biochemical characteristics in vitro; however, the assessments of their clinical applications in vivo are restricted by their limited bioavailability due to their strong resistance to 1st-pass effectsduring absorption. In order to improve the bioavailability of quercetin (QU), the ester derivative of QU (3,3,4,5,7-pentahydroxy flavones, TAQU) was synthesized, followed by examining the oil-water partition coefficient as well as the transport mechanisms of QU and its ester derivative (TAQU) using human Caco-2 cells. The transport characteristics of QU and TAQU transport under different conditions (different concentrations, time, pH, temperature, tight junctions, and potential transporters) were systematically investigated. Results showed that QU had a lower permeability coefficient (2.82 x 10(-6) cm/s) for apical-to-basolateral (AP-BL) transport over 5 to 50 M, whereas the transport rate for AP to BL flux of TAQU (5.23 x 10(-6) cm/s) was significantly greater than that of QU. Paracellular pathways were not involved during the transport of both QU and TAQU. QU was poorly absorbed by active transport, whereas TAQU was mostly absorbed by passive diffusion. Efflux transporters, P-glycoproteins, multidrug resistance proteins were proven to participate in the transport process of QU, but not in that of TAQU. These results suggested that improving the lipophicity of QU by esterification could increase the transport of QU across Caco-2 cells.Practical Application The ester derivative of quercetin (TAQU) was synthesized to improve the bioavailability of QU, and its transport efficiency was proved by using Caco-2 cells. Results suggested that improving the lipophicity of QU by esterification could increase the transport across Caco-2 cells. Thus, this study may provide a useful strategy for molecular structure modification to improve intestinal absorption of hydrophilic compounds.