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. 2023 Jan 21;12(3):503.
doi: 10.3390/foods12030503.

Effects of 6-Shogaol on Glucose Uptake and Intestinal Barrier Integrity in Caco-2 Cells

Wenya Jiao  1 , Yaxin Sang  1 , Xianghong Wang  1 , Shuo Wang  2
Affiliations

Effects of 6-Shogaol on Glucose Uptake and Intestinal Barrier Integrity in Caco-2 Cells

Wenya Jiao et al. Foods. .

Abstract

As the main bioactive component in dried ginger, 6-shogaol has potential hypoglycemic activity, but its mechanism is still unclear. The process of carbohydrate digestion and glucose absorption is closely related to the enzymatic activity of epithelial brush cells, expression of glucose transporters, and permeability of intestinal epithelial cells. Therefore, this study explored the hypoglycemic mechanism of 6-shogaol from the perspective of glucose uptake, absorption transport, and protection of intestinal barrier function. Based on molecular docking, the binding energy of 6-shogaol and α-glucosidase is -6.24 kcal/mol, showing a high binding affinity. Moreover, a-glucosidase enzymatic activity was reduced (-78.96%) when the 6-shogaol concentration was 500 µg/mL. After 6-shogaol intervention, the glucose uptake was reduced; the relative expression of glucose transporters GLUT2 and SGLT1 were down regulated; and tight junction proteins ZO-1, Occludin and Claudin were up regulated in differentiated Caco-2 cells. This study confirmed that 6-shogaol effectively inhibits the activity of α-glucosidase and has beneficial effects on glucose uptake, protection of intestinal barrier function, and promotion of intestinal material absorption.

Keywords: 6-shogaol; Caco-2 cells; barrier function; glucose uptake.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular models of 6-shogaol and acarbose binding to α-glucosidase protein: (A) 3D model of 6-shogaol and α-glucosidase (PDBID:3A4A) crystal structure docking. (B) 2D model of 6-shogaol and α-glucosidase docking. (C) 3D model of acarbose and α-glucosidase (PDBID:3A4A) crystal structure docking. (D) 2D model of acarbose and α-glucosidase docking.
Figure 2
Figure 2
Inhibition of α-glucosidase activity by 6-shogaol.
Figure 3
Figure 3
Change in TEER value of Caco-2 cells within 21 days. * represents significance, as compared with the TEER value on the 7th day (** p < 0.01).
Figure 4
Figure 4
Effect of 6-shogaol on the metabolic activity of Caco-2 cells. * represents significance, as compared to control group (* p < 0.05).
Figure 5
Figure 5
Effect of 6-shogaol on glucose consumption in Caco-2 cells. # compared with blank (### p < 0.001), * represents significance, as compared to control group (*** p < 0.001, ** p < 0.01, * p < 0.05).
Figure 6
Figure 6
Effect of 6-shogaol on the expression of related proteins in Caco-2 cells. (A) The expressions of ZO-1, Occludin, Claudin, GLUT2, and SGLT1 were analyzed by Western blot. (B–F) The quantitative analysis of protein expressions in Caco-2 cells. * represents significance, as compared to control cells (** p < 0.01, * p < 0.05).
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