Ameliorative Effects of Pumpkin Seed Protein Peptides on Dexamethasone-Treated Sarcopenia and Their Effects When Combined with Vitamin D

Sarcopenia is a degenerative condition that imposes a substantial global public health burden, yet safe and effective interventions remain limited. Nutritional support is regarded as an important strategy to mitigate age-related muscle loss and improve physical function in older adults. Due to time and cost constraints, dexamethasone (DEX)-treated models are often used as an alternative to age-related sarcopenia models. This study investigated the effects of pumpkin seed protein peptides (PSPP) and vitamin D on DEX-treated mice. In vitro, PSPP attenuated senescence-associated phenotypes, reduced cellular injury, and partially alleviated DEX-treated myofibrillar atrophy, as evidenced by decreased Atrogin-1 and MuRF1 expression and increased MyoD expression. In vivo, PSPP and vitamin D, particularly in combination, ameliorated DEX-treated declines in muscle mass, grip strength, and endurance. Histological analyses further demonstrated improvements in myofibrillar architecture and muscle fiber cross-sectional area. In addition, each intervention was associated with increased ATP content, elevated interleukin-10 and insulin-like growth factor-1 levels, and reduced tumor necrosis factor-α and malondialdehyde levels. Collectively, these findings suggest that PSPP, either alone or combined with vitamin D, may alleviate DEX-treated sarcopenia, potentially through the modulation of mitochondrial homeostasis, attenuation of oxidative stress and inflammatory responses, and promotion of myogenic regeneration.