Molecular Mechanisms Underlying the Absorption of Aglycone and Glycosidic Flavonoids in a Caco-2 BBe1 Cell Model

Hua Zhang; Yousef I Hassan; Ronghua Liu; Lili Mats; Cheng Yang; Chunming Liu; Rong Tsao

doi:10.1021/acsomega.0c00379

Molecular Mechanisms Underlying the Absorption of Aglycone and Glycosidic Flavonoids in a Caco-2 BBe1 Cell Model

ACS Omega. 2020 May 6;5(19):10782-10793. doi: 10.1021/acsomega.0c00379. eCollection 2020 May 19.

Authors

Hua Zhang¹, Yousef I Hassan¹, Ronghua Liu¹, Lili Mats¹, Cheng Yang², Chunming Liu³, Rong Tsao¹

Affiliations

¹ Guelph Research & Development Centre, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, Ontario N1G 5C9, Canada.
² Food Science Department, Jiangnan University, 1800 Lihu Avenue, Binhu Qu, Wuxi Shi, Jiangsu Province 214122, China.
³ Central Laboratory, Changchun Normal University, No. 677 North Chang-ji Road, Changchun 130032, China.

Abstract

The mechanisms of cellular absorption and transport underlying the differences between flavonoid aglycones and glycosides and the effect of the structural feature are not well established. In this study, aglycone, mono-, and diglycosides of quercetin and cyanidin were selected to examine the effects of the structural feature on the bioavailability of flavonoids using hexose transporters SGLT1 and GLUT2 in a Caco-2 BBe1 cell model. Cellular uptake and transport of all glycosides were significantly different. The glycosides also significantly inhibited cellular uptake of d-glucose, indicating the involvement of the two hexose transporters SGLT1 and GLUT2 in the absorption, and the potential of the glycosides in lowering the blood glucose level. The in silico prediction model also supported these observations. The absorption of glycosides, especially diglycosides but not the aglycones, was significantly blocked by SGLT1 and GLUT2 inhibitors (phloridzin and phloretin) and further validated in SGLT1 knockdown Caco-2 BBe1 cells.