Issue 13, 2025

Comprehensive analysis of yak milk residue peptides for anti-hypoxic functional foods: targeting neuroinflammation and apoptosis in hypoxic mice

Abstract

The hypoxia-induced stress response constitutes a physiological disorder that poses a significant, life-threatening risk. This study aims to investigate the anti-hypoxic brain injury effects of peptides derived from yak milk residue and elucidate their underlying mechanisms. Peptidomic analysis identified three bioactive peptides (YPFPGPIPN, PVVPPFLQPEVMGVSK, and T3-LVYPFPGPIPN (T3)) associated with anti-hypoxic activity. In vitro blood–brain barrier (BBB) modeling demonstrated that T3 exhibited significant time- and concentration-dependent permeability. Under hypoxic stress, T3 effectively inhibited neuronal inflammation and apoptosis. Integrated metabolomics and transcriptomics analyses revealed that T3 mitigates hypoxia-induced neuroinflammation by regulating L-glutamine metabolism through the RAS/TNF-α/MAPK signaling pathway. These findings underscore the potential of yak milk residue-derived peptide (T3) as a neuroprotective agent against hypoxic injury. The insights gained from this research are instrumental in utilizing yak milk byproducts and developing functional foods with anti-hypoxia properties, thereby addressing the market needs of specific demographic groups.

Graphical abstract: Comprehensive analysis of yak milk residue peptides for anti-hypoxic functional foods: targeting neuroinflammation and apoptosis in hypoxic mice

Supplementary files

Article information

Article type
Paper
Submitted
10 Mar 2025
Accepted
14 Jun 2025
First published
19 Jun 2025

Food Funct., 2025,16, 5632-5651

Comprehensive analysis of yak milk residue peptides for anti-hypoxic functional foods: targeting neuroinflammation and apoptosis in hypoxic mice

F. Yang, Z. Luo, Z. Chu, Z. He, Z. Hu, G. Qu, Y. Zhou, Y. Tang, S. Sun and F. Luo, Food Funct., 2025, 16, 5632 DOI: 10.1039/D5FO01223F

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