Key Laboratory of Environment Correlative Dietology (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, PR China.
Food Chem. 2019 Sep 1;291:101-109. doi: 10.1016/j.foodchem.2019.03.111. Epub 2019 Mar 21.
This study was aimed to determine the relationship of flavonoid structures to their affinity for an important efflux transporter, multidrug-resistant associated protein 2 (MRP2). The cellular uptake (CU) of 35 flavonoids was investigated in MRP2 overexpression MDCK/MRP2 cells. Resulting data identified 8 flavonoids as MRP2 substrates based on their high CU with MK-571 in MDCK/MRP2 cells. Also, three substrates showed better CU in MDCK cells than did CU in MDCK/MRP2 cells. Docking analyses showed a good correlation (R = 0.926, p = 0.003) between efflux-fold of flavonoid substrates and their docking S_scoring with the MRP2 model, indicating consistency between in silico and in vitro approaches. A structure affinity relationship (SAR) study indicated that 3-OH, 5-OH, 6-OH, 3'-OH, and 4'-OCH substituents were favourable while, 8-OCH, 2'-OH, 3'-OCH, 4'-OH and 5'-OH were unfavourable for flavonoid affinity to MRP2. Our study provides valuable information for dietary application of flavonoids with specific structures for high absorption.
本研究旨在确定黄酮类化合物结构与其对重要外排转运蛋白多药耐药相关蛋白 2 (MRP2) 的亲和力之间的关系。在过表达 MRP2 的 MDCK/MRP2 细胞中研究了 35 种黄酮类化合物的细胞摄取 (CU)。结果数据根据黄酮类化合物在 MDCK/MRP2 细胞中与 MK-571 的高 CU，确定了 8 种黄酮类化合物为 MRP2 底物。此外，三种底物在 MDCK 细胞中的 CU 优于在 MDCK/MRP2 细胞中的 CU。对接分析显示，黄酮类化合物底物的外排倍数与其与 MRP2 模型的对接 S 评分之间存在良好的相关性 (R = 0.926，p = 0.003)，表明了计算机模拟和体外方法之间的一致性。结构亲和力关系 (SAR) 研究表明，3-OH、5-OH、6-OH、3'-OH 和 4'-OCH 取代基是有利的，而 8-OCH、2'-OH、3'-OCH、4'-OH 和 5'-OH 则不利于黄酮类化合物与 MRP2 的亲和力。我们的研究为具有特定结构的黄酮类化合物在高吸收方面的饮食应用提供了有价值的信息。
