A composite arctigenin/caffeine/glucose formulation enhances anti-fatigue effect

Fatigue is a comprehensive response to a variety of physiological and biochemical changes in the body. Combining strategies addressing relevant key factors simultaneously may enhance anti-fatigue efficiency. In this study, we aimed to develop new anti-fatigue agents with combining strategy based on bioinformatics analysis. Result indicated PI3k-Akt, cAMP, and p53 signaling pathway-related energy metabolism and antioxidant capacity were involved in exercise-induced physiological changes. A new representative complex agent (Z-005, containing arctigenin, caffeine, and glucose) addressing these key factors as well as central excitation was developed and tested. Z-005 showed a synergistic effect, greatly enhancing anti-fatigue efficiency than single components, in a mouse running wheel test. Mouse exhaustion distances were 2.40-fold greater than the control in the Z-005 group. Z-005 excited the central nervous system, increased the plasma superoxide dismutase and catalase concentrations, reduced lactic acid accumulation, maintained the glycogen content. Besides, the expression of key genes in PI3K, cAMP, and p53 pathways, as well as the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) were proved with enhancement by Z-005 administration. This composite formulation thus represents a new and practicable combined strategy for fatigue prevention, and the study findings can contribute to the development of treatments for fatigue-related sub-health.