Curcumin and bisdemethoxycurcumin inhibit glucose and enhance fructose absorption in differentiated Caco-2 cells, while dibenzoylmethane inhibits glucose absorption

Excessive saccharide intake contributes to type 2 diabetes development. Polyphenols may decrease saccharide absorption in the small intestine. We investigated the potential of curcuminoids to modulate glucose and fructose absorption and expression of saccharide transporters SGLT1 and GLUT5 in differentiated Caco-2 cells. We also examined the impact of glucose-to-fructose ratios on curcumin's ability to inhibit saccharide absorption. Caco-2 cells were pre-exposed to 1 mM phloretin, 500 µM phlorizin, 400 µM dibenzoylmethane, 200 µM curcumin, or 200 µM bisdemethoxycurcumin for 4 h followed by a 30-min exposure to different glucose-to-fructose ratios. Basolateral glucose and NBD-fructose levels were measured, along with SGLT1, GLUT5, and MLCK1 expression. FITC-dextran absorption was assessed to evaluate paracellular fructose absorption. All reported changes were statistically significant (p < 0.05). Dibenzoylmethane reduced glucose absorption by 50 % and SGLT1 expression by 45 %. Curcumin decreased glucose absorption by 72 % and SGLT1 expression by 25 %. Bisdemethoxycurcumin led to a 37 % reduction in glucose absorption and an 80 % decrease in SGLT1 expression. Interestingly, curcumin and bisdemethoxycurcumin increased basolateral NBD-fructose concentrations by 170 % and 105 %, respectively, without any changes in GLUT5 expression. Higher glucose-to-fructose ratios reduced curcumin's inhibitory effect on glucose absorption by 15 %, but did not affect fructose absorption stimulation. Lower fructose eliminated curcumin's fructose absorption stimulation. Curcumin increased FITC-dextran permeation by 20 % across ratios, suggesting increased paracellular permeability. In contrast, MLCK1 expression decreased by 30 %. In conclusion, dibenzoylmethane demonstrated potent inhibition of glucose absorption and SGLT1 expression, while curcumin and bisdemethoxycurcumin decreased glucose absorption and enhanced fructose absorption in differentiated Caco-2 cells.