Ameliorative effect of sea cucumber on physical fatigue induced by forced ambulation and its underlying mechanism

Fatigue represents a significant health concern. Chronic fatigue may contribute to mental health disorders and accelerated aging. Oxidative stress, characterized by excessive production of reactive oxygen species, is generally considered to increase during physical exertion and to indicate fatigue. Although antioxidants are known to enhance endurance, effects of sea cucumber (SC) on physical fatigue remain undetermined and were explored in this study. We investigated the effects of SC on alterations in locomotor activity and expression levels of silent mating type information regulation 2 homolog peroxisome 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (NRF2), and antioxidative-related proteins, including superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1), and catalase, in the soleus muscle following SC administration before and/or after forced walking. Administration of SC before and after forced walking, rather than at a single time point, mitigated the subsequent decrease in locomotor activity and enhanced expression of Sirt1, NRF2, SOD1, GPx1 and catalase in the soleus muscle of mice. In contrast, EX-527, the selective Sirt1 inhibitor, abolished the SC-induced anti-fatigue effect and the enhanced Sirt1/NRF2/SOD1-GPx1-catalase pathway in the soleus muscle. Consequently, we propose that SC attenuates fatigue by modulating the Sirt1/NRF2/SOD1-GPx1-catalase pathway in the soleus muscle.