Mechanisms of fatigue and molecular diagnostics: The application of bioactive compounds in fatigue relief research

Fatigue represents a complex biopsychological phenomenon encompassing two distinct yet interrelated dimensions: mental fatigue (subjective perception) and physical fatigue (objective performance) that emerge during sustained cognitive exertion and intensive physical training regimens. Rapid fatigue can negatively impact work efficiency and quality of life, which is especially problematic for particular groups, such as those doing heavy mental work, athletes, astronauts, and soldiers. Furthermore, persistent fatigue increases the likelihood of developing a disease or reduces lifespan. Bioactive compounds (polysaccharides, peptides, polyphenols, saponins, etc.) from natural products offer easily accessible resources for effectively relieving fatigue. This review summarizes the potential molecular mechanisms of fatigue, including the regulation of Ca²⁺, energy substance depletion, the inflammatory factor storm, and the oxidative stress reaction. In addition, bioactive compounds in natural products that can relieve fatigue, as well as the underlying pathophysiological mechanisms, are discussed. Understanding the mechanism of fatigue development and its consequences can help prolong the time for fatigue occurrence, alleviate the severity of fatigue, reduce the duration of persistent fatigue, and allow the prediction of fatigue based on biomarker detection. Ultimately, effective ways to relieve fatigue can be identified through the mechanism of fatigue and offer insights for the development of functional foods and beverages.