Egg white-derived metabolic regulatory peptide AD-IR10 promotes diabetic wound healing via Keap1/Nrf2/Irg1-mediated
Dan Sun1, Ting Su1, Xingtang Niu1
1Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Abstract:
Chronic diabetic wounds are characterized by oxidative stress and persistent inflammation, largely due to dysregulated macrophage polarization. Here, a decapeptide, ADHPFLFFIR (AD-IR10), derived from egg white hydrolysate, was identified as a modulator of the Keap1-Nrf2 pathway. AD-IR10 reduces oxidative stress and reprograms macrophage metabolism via the IRG1-itaconate axis, shifting macrophages from pro-inflammatory M1 to reparative M2 phenotypes. Integrated transcriptomic and metabolomic analyses revealed that Nrf2 activation by AD-IR10 enhances itaconate accumulation, suppresses glycolysis, and promotes oxidative phosphorylation in the TCA cycle. Functional assays demonstrated that AD-IR10 treated macrophages display improved mitochondrial function and anti-inflammatory activity. In a diabetic mouse wound model, topical administration of AD-IR10 accelerated wound closure, increased angiogenesis and collagen deposition, and enhanced M2 macrophage infiltration. These results identify AD-IR10 as a food-derived peptide capable of modulating macrophage immunometabolism, offering a promising therapeutic strategy for chronic diabetic wound repair.
