Structure affinity relationship and docking studies of flavonoids as substrates of multidrug-resistant associated protein 2 (MRP2) in MDCK/MRP2 cells. (1st September 2019)

• Record Type: Journal Article
• Authors: Fang, Yajing; Cao, Weiwei; Liang, Fuqiang; Xia, Mengmeng; Pan, Siyi; Xu, Xiaoyun
• Is Part Of: Food chemistry. Volume 291(2019)
• Page Start: 101
• Page End: 109
• Publication Date: 2019-09-01
• Subjects: Flavone (PubChem CID: 10680) -- Tangeretin (PubChem CID: 68077) -- Chrysin (PubChem CID: 5281607) -- Baicalein (PubChem CID: 5281605) -- Wogonin (PubChem CID: 5281703) -- Apigenin (PubChem CID: 5280443) -- Luteolin (PubChem CID: 5280445) -- Vitexin (PubChem CID: 5280441) -- Isovitexin (PubChem CID: 162350) -- Schaftoside (PubChem CID: 442658) -- Galangin (PubChem CID: 5281616); Cellular uptake -- Flavonoids -- MRP2 -- Structure affinity relationship -- Substrates; Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; 664
• DOI: 10.1016/j.foodchem.2019.03.111
• Languages: English
• ISSNs: 0308-8146

Abstract

Highlights: MRP2 was stably expressed in MDCK/MRP2 cells. 8 of 35 flavonoids were identified as substrates of MRP2 in MDCK/MRP2 cells. SAR and docking were done for structure requirements of flavonoid substrates. 3, 5, 6, 3′-OH, 4′-OCH3 favoured but 8, 3′-OCH3, 2′, 4′, 5′-OH disfavoured for MRP2 affinity. Abstract: 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 CUMK with MK-571 in MDCK/MRP2 cells. Also, three substrates showed better CUMD in MDCK cells than did CUMRP 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′-OCH3 substituents were favourable while, 8-OCH3, 2′-OH, 3′-OCH3, 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.