Identification of DPP-IV Inhibitory Peptides from Eggshell Membranes: Structure-Activity Relationships, Digestive...

Area of Science:

• Biochemistry
• Food Science
• Pharmacology

Background:

• Eggshell membrane (ESM) is an underutilized protein-rich byproduct.
• ESM contains bioactive sequences with physiological relevance.
• Dipeptidyl peptidase-IV (DPP-IV) inhibitors are crucial for managing type 2 diabetes.

Purpose of the Study:

• To explore ESM as a novel source of DPP-IV inhibitory peptides.
• To identify and characterize bioactive peptides from ESM.
• To elucidate the structure-activity relationship and potential mechanisms of these peptides.

Main Methods:

• Enzymatic hydrolysis of ESM using various proteases.
• Assay of DPP-IV inhibitory activity of hydrolysates.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for peptide identification.
• Molecular docking and network pharmacology for mechanistic insights.

Main Results:

• Alkaline protease hydrolysis yielded the most effective DPP-IV inhibitory activity.
• Novel peptides, including APSPWE, LFPVTPN, and GPPHFLPF, were identified.
• APSPWE exhibited potent DPP-IV inhibition (IC50 = 246 μM) and in situ activity in Caco-2 cells.
• APSPWE may modulate glucose-regulatory pathways via TNF, IL-17, AGE-RAGE, and insulin signaling.

Conclusions:

• ESM is a valuable source for discovering DPP-IV inhibitory peptides.
• Peptide structure, particularly N-terminal hydrophobic residues and specific second amino acids, correlates with inhibitory activity.
• Identified peptides, like APSPWE, show potential for functional food ingredients or therapeutic agents targeting glucose metabolism.