A Prunus avium L. Infusion Inhibits Sugar Uptake and Counteracts Oxidative Stress-Induced Stimulation of Glucose Uptake by Intestinal Epithelial (Caco-2) Cells

Abstract

Sweet cherry (Prunus avium L.) is among the most valued fruits due to its organoleptic properties and nutritional worth. Cherry stems are rich in bioactive compounds, known for their anti-inflammatory and antioxidant properties. Innumerable studies have indicated that some bioactive compounds can modulate sugar absorption in the small intestine. In this study, the phenolic profile of a cherry stem infusion was investigated, as well as its capacity to modulate intestinal glucose and fructose transport in Caco-2 cells. Long-term (24 h) exposure to cherry stem infusion (25%, v/v) significantly reduced glucose (³H-DG) and fructose (¹⁴C-FRU) apical uptake, reduced the apical-to-basolateral P_app to ³H-DG, and decreased mRNA expression levels of the sugar transporters SGLT1, GLUT2 and GLUT5. Oxidative stress (induced by tert-butyl hydroperoxide) caused an increase in ³H-DG uptake, which was abolished by the cherry stem infusion. These findings suggest that cherry stem infusion can reduce the intestinal absorption of both glucose and fructose by decreasing the gene expression of their membrane transporters. Moreover, this infusion also appears to be able to counteract the stimulatory effect of oxidative stress upon glucose intestinal uptake. Therefore, it can be a potentially useful compound for controlling hyperglycemia, especially in the presence of increased intestinal oxidative stress levels.

Keywords: antioxidant activity; cherry stem; infusion; intestinal sugar uptake; phenolic compounds.

Figure 1

Effect of cherry stem infusion on the uptake of (a) ³H-DG and (b) ¹⁴C-FRU by Caco-2 cells. Caco-2 cells were exposed for 24 h to the cherry stem infusion (250 µL/mL) or the respective vehicle (control) (n = 10). Data are shown as mean ± S.E.M., by Student’s t-test. ** p < 0.01; **** p < 0.0001 significantly different from control.

Figure 2

Effect of cherry stem infusion on the apical-to-basolateral (AP−BL) apparent permeability (P_app) to (a) ³H-DG and (b) ¹⁴C-FRU and on the cellular content of (c) ³H-DG and (d) ¹⁴C-FRU (n = 6–7) Data are shown as mean ± S.E.M., by Student’s t-test. * p < 0.05; ** p < 0.01 significantly different from control.

Figure 3

Effect of cherry stem infusion on sodium-dependent glucose cotransporter (SGLT1), facilitative glucose transporter 2 (GLUT2) and facilitative glucose transporter 5 (GLUT5) mRNA levels in Caco-2 cells (n = 6–7). Data were normalized to the expression of β-actin. Data are shown as mean ± S.E.M., by Student’s t-test. * p < 0.05; ** p < 0.01 significantly different from control.

Figure 4

Effect of cherry stem infusion, N−acetylcysteine (NAC) and ascorbic acid, on the uptake of ³H-DG by Caco-2 cells, in the presence and absence of tert−butylhydroperoxide (TBH) (n = 8). Uptake was measured by incubating Caco-2 cells at 37 °C with ³H-DG (10 nM) for 6 min. Data are shown as mean ± S.E.M., by two-way ANOVA with Newman-Keuls post hoc test. ** p < 0.01; *** p < 0.001; **** p < 0.0001 significantly different from control; # p < 0.01 significantly different from TBH.