Excavation of Lentinula edodes-stem-derived peptides doubly inhibiting DPP-IV and ACE activity.

Type Ⅱ diabetes and hypertension often coexist, affecting each other. Suppressing dipeptidyl peptidase-4 (DPP-Ⅳ) and angiotensin-I-converting enzyme (ACE) activity is crucial for managing these conditions. Lentinula edodes-stem protein, rich in hydrophobic amino acids, has potential for creating DPP-Ⅳ and ACE inhibitory peptides. This study used this protein, combined with databases, to derive peptides that exhibit dual inhibition of DPP-Ⅳ and ACE activity via enzymatic hydrolysis by Bacillus subtilis protease. The most active fraction (F1-2) had IC50 values of 0.0910 mg/mL (DPP-Ⅳ) and 0.0189 mg/mL (ACE). Following the sequencing of fraction F1-2, screening, and solid-phase synthesis, three novel peptides (EW-1, WR-2, and LP-3) exhibiting >60% inhibition of both DPP-Ⅳ and ACE at 1 mg/mL. These peptides showed no significant toxicity to Caco-2 cells, indicating safety. These findings suggest that peptides derived from the stem of Lentinula edodes are promising candidates for health products targeting type Ⅱ diabetes and hypertension.