The Effect of Ferulic Acid-Grafted Chitosan (FA-g-CS) on the Transmembrane Transport of Anthocyanins by sGLT1 and GLUT2

Abstract

This work aims to evaluate the effect of ferulic acid-grafted chitosan (FA-g-CS) on the interaction between anthocyanin (ANC) and sGLT1/GLUT2 and their functions in ANC transmembrane transport using Caco-2 cells. The transmembrane transport experiments of ANC showed its low transport efficiency (Papp < 10−6 cm/s), whereas the phenomenon of a significantly rise in anthocyanins transport efficiency was observed with the incubation of FA-g-CS (p < 0.05). In order to investigate the mechanism of FA-g-CS improving ANC transmembrane transport, Caco-2 cells were transfected with small interfering RNA (siRNA) specific for transporters sGLT1 and GLUT2, and incubated with ANC, FA-g-CS, or their combination. Subsequently, Western blot analyses and immunofluorescence staining were carried out to monitor the intracellular sGLT1 and GLUT2 levels. These siRNA-transfected cells, incubated with compounds, indicate that sGLT1 and GLUT2 participated in the ANC transmembrane transport and that FA-g-CS, ANC, or their combination enhance sGLT1/GLUT2 expression. In particular, Caco-2 cells incubated with both FA-g-CS and ANC show significantly increased sGLT1 or GLUT2 expression (>80%) compared with exclusively using FA-g-CS or ANC (<60%). Molecular docking results demonstrate that there is a good binding between FA-g-CS/ANC and sGLT1 or GLUT2. These results highlight that FA-g-CS promotes the transmembrane transport of ANC by influencing the interaction between ANC and sGLT1/GLUT2; the interaction between FA-g-CS and ANC could be another key factor that improves the bioavailability of ANC.

Physiological functions of glucose transporter-2: From cell physiology to links with diabetes mellitus

“…However, the specific biological functions of GLUT-2 in diabetes remain unclear, and whether the transporter performs other physiological functions in the gut is still unexplored. Thus, the designed targeted drugs may cause metabolic disorders and damage the natural barrier function of the small intestine, causing an imbalance of normal intestinal flora [ 89 , 90 ]. Nonetheless, altering GLUT-2 activity is still a constructive drug design idea for treating diabetes.…”