Digestion Characteristics of Yeast Protein and Identification of Bioactive Peptides with Cytoprotective Effects against LPS-Induced Injury in C2C12 Myoblasts

Abstract

Yeast protein (YP) is a sustainable alternative protein, offering a favorable amino acid profile. However, its digestion kinetics and potential as a source of bioactive peptides (BAPs) remain neglected. This study applied the INFOGEST digestion model to compare in vitro digestion kinetics of YP, whey and soy protein. YP exhibited delayed amino acid release and distinct proteomic features. Analysis of the final intestinal chyme of YP identified 312 unique peptides. In silico screening identified several low-molecular-weight peptides (<1000 Da) with high bioactivity potential and favorable pharmacokinetics. Crucially, cell-based assays revealed that two high-abundance peptides, GDWPLPT and PLPPAPAPK, significantly alleviated lipopolysaccharide (LPS)-induced injury in C2C12 myotubes. These peptides reduced reactive oxygen species (ROS) levels and interleukin-6 (IL-6) secretion, while restoring mitochondrial membrane potential and adenosine triphosphate (ATP) synthesis. Overall, this study provides a comprehensive characterization of the digestion kinetics and peptide profiles of YP. Beyond these findings, the cytoprotective potential of the identified peptides was validated in a muscle injury model, thereby proving YP as a promising source of functional food ingredients for future applications.