PUBLICATION
Hydrolyzed Milk-Derived Peptides Promote Erythropoietin Pathways and Hematologic Recovery: A Cross-Species Analysis
- Authors
- Zang, L., Yokota, A., Nakai, M., Fukada, K., Nishimura, N., Shimada, Y.
- ID
- ZDB-PUB-251231-13
- Date
- 2025
- Source
- Molecules 30: (Journal)
- Registered Authors
- Shimada, Yasuhito
- Keywords
- EPO-iron axis, bioactive peptides, cross-species model, erythroid differentiation, hematopoietic regulation, nutraceutical
- MeSH Terms
-
- Anemia*/blood
- Anemia*/drug therapy
- Anemia*/metabolism
- Animals
- Cytokines/blood
- Disease Models, Animal
- Erythropoiesis/drug effects
- Erythropoietin*/genetics
- Erythropoietin*/metabolism
- Hemoglobins/metabolism
- Hydrolysis
- Iron/metabolism
- Mice
- Milk*/chemistry
- Peptides*/chemistry
- Peptides*/pharmacology
- Signal Transduction/drug effects
- Zebrafish
- PubMed
- 41471763 Full text @ Molecules
Citation
Zang, L., Yokota, A., Nakai, M., Fukada, K., Nishimura, N., Shimada, Y. (2025) Hydrolyzed Milk-Derived Peptides Promote Erythropoietin Pathways and Hematologic Recovery: A Cross-Species Analysis. Molecules. 30:.
Abstract
Anemia, characterized by reduced hemoglobin (Hb), remains a major health concern. Although iron and erythropoietin (EPO) therapies are effective, limitations in safety and accessibility have prompted interest in nutritional alternatives. Hydrolyzed milk-derived peptides (H-MDPs) contain bioactive sequences with diverse physiological effects, yet their role in erythropoiesis remains poorly defined. This study investigated the hematopoietic actions of H-MDP using zebrafish and mouse models. Adult zebrafish underwent phlebotomy-induced anemia and received oral H-MDP for 3 weeks. Hb levels, erythrocyte morphology, and expression of erythropoiesis- and iron-metabolism genes were assessed. In healthy mice, renal Epo expression, circulating EPO, and serum cytokines were measured after 2 weeks of H-MDP administration. H-MDP significantly accelerated Hb recovery in anemic zebrafish (4.6 ± 0.64 g/dL vs. 3.4 ± 0.66 g/dL in untreated fish at week 1) and markedly improved erythrocyte maturation. These effects coincided with strong induction of epo, hif1aa/b, igf1, csf1a, and csf3b in the heart and liver, as well as normalization of anemia-induced hepatic iron-transport genes (tfa, fpn1, tfr2) and reactivation of hamp. In mice, H-MDP elevated renal Epo mRNA and circulating EPO (approximately 2.3-fold) without altering steady-state Hb, and cytokine profiling with IPA-predicted activation of the erythropoietin signaling pathway. Collectively, these findings indicate that H-MDPs modulate erythropoiesis by coordinating the activation of EPO-related and iron-regulatory networks, supporting their potential as functional food ingredients for hematologic recovery and anemia management.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping