Multidimensional study of DPP-IV inhibitory peptides from phycocyanin: Screening, identification, inhibitory...

Dipeptidyl peptidase IV (DPP-IV) inhibitors are well known medication for type 2 diabetes mellitus. The present study aimed to prepare and screen DPP-IV inhibitory peptides from phycocyanin (PC) and investigate their inhibition types and cellular transportation mechanism.

PC was hydrolyzed using four different enzymes, Neutrase hydrolysates (10.0 mg mL^-1) showed the best DPP-IV inhibitory activity, with an percentage inhibitory rate of 73.65%. The optimal hydrolysis conditions obtained by single-factor experiments were: neutrase, enzyme concentration of 3.0%, solid-liquid ratio of 1:30 g mL^-1, hydrolysis time of 3.0 h, hydrolysis temperature of 50.0 °C and pH 7.0, under which the hydrolysates showed an IC₅₀ value of 2.72 ± 0.15 mg mL^-1. Gastrointestinal digestion can improve the DPP-IV inhibition of hydrolyates. Animal experiments demonstrated that oral administration of PC hydrolysates significantly reduced the FBG and glycated serum protein levels, improved glucose tolerance ability, attenuated insulin resistance, and alleviated lipid disturbance of type II diabetic mice. Two novel DPP-IV inhibitory peptides, IASY and IAGIDE, with IC₅₀ values of 0.22 ± 0.01 mg mL^-1 and 0.38 ± 0.02 mg mL^-1, respectively, were separated and characterized from the < 3.0 kDa fraction of PC hydrolysates using affinity ultrafiltration and molecular docking techniques. Both peptides exhibited a mixed inhibition pattern against DPP-IV, and bound to the active site of DPP-IV mainly through hydrogen bonds and hydrophobic interactions. IASY showed better biocompatibility and absorption transport rate than IAGIDE in Caco-2 cells.

This study showed that peptides from PC, especially IASY and IAGIDE, have therapeutic potential in blood glucose management. © 2026 Society of Chemical Industry.