Enzyme-modified and fermented pea protein (EFPP) containing IQRPVKEL and IENPVKEL attenuate dexamethasone-induced muscle atrophy via FoxO3 signaling in C2C12 myotubes

Abstract This study examined the potential of enzyme-modified and fermented pea protein (EFPP) to mitigate muscle atrophy by assessing the changes of muscle atrophy-related factors and mitochondrial biogenesis markers in C2C12 cells treated with dexamethasone (DEX). C2C12 cells treated with 40–80 µg/mL EFPP showed significant increases in myotube length and upregulated expression of muscle differentiation markers MyoD1 and Myogenin. Moreover, EFPP improved mitochondrial biogenesis, as indicated by elevated gene and protein levels of Sirt1, AMPK, and PGC1α in the DEX-induced muscle atrophy cells. EFPP also significantly downregulated gene expression of FoxO3a, Atrogin-1, and MuRF-1. Two bioactive peptides, IQRPVKEL and IENPVKEL, derived from EFPP, further demonstrated protective effects by upregulating mitochondrial biogenesis markers while reducing muscle atrophy factors. These findings suggest that EFPP can prevent muscle degradation and promote muscle differentiation, offering potential therapeutic benefits for muscle health.