Longan seed-derived peptides inhibit glucose transport via modulation of SGLT1 and GLUT2 in Caco-2 cells

Abstract

This study presents the first evidence of the ability of two synthetic peptides, SA-10 (SSYYPFKGFA) and VI-10 (VKGPGLYSDI), derived from longan seed hydrolysates to inhibit intestinal glucose absorption via SGLT1 and GLUT2 transporters. Molecular docking revealed strong binding affinities: SA-10 to SGLT1 (−9.1 kcal/mol) and VI-10 to GLUT2 (−8.7 kcal/mol), involving hydrogen bonds and hydrophobic interactions at key glucose-binding sites, suggesting competitive inhibition. Molecular dynamics simulations over 100 ns supported these findings, demonstrating structural stability and compactness of the peptide-transporter complexes, as indicated by sustained RMSD and Rg values throughout the simulation trajectory. In vitro assays using Caco-2 cells showed that both peptides significantly reduced glucose uptake in a dose- and time-dependent manner, achieving approximately 50% reduction at 1.00 mM after 3 h. Western blot analysis confirmed SA-10 downregulated SGLT1 expression, while VI-10 reduced both SGLT1 and GLUT2 levels. These findings suggest that longan seed-derived peptides can modulate both glucose uptake and transporter expression in intestinal cells. Importantly, SA-10 and VI-10 represent novel glucose transporter inhibitors and hold promise for development as functional food ingredients or nutraceuticals to manage postprandial hyperglycemia and support glycemic control in diabetes management.