Signaling pathways regulated by natural active ingredients in the fight against exercise fatigue-a review

Abstract

Exercise fatigue is a normal protective mechanism of the body. However, long-term fatigue hinders normal metabolism and exercise capacity. The generation and recovery from exercise fatigue involves alterations in multiple signaling pathways, mainly AMPK, PI3K/Akt, Nrf2/ARE, NF-κB, PINK1/Parkin, and BDNF/TrkB, as well as MAPK signaling pathways that mediate energy supply, reduction of metabolites, oxidative stress homeostasis, muscle fiber type switching, and central protective effects. In recent studies, a rich variety of natural active ingredients have been identified in traditional Chinese medicines and plant extracts with anti-fatigue effects, opening up the field of research in new anti-fatigue drugs. In this review we give an overview of the signaling pathways associated with the activity of natural food active ingredients against exercise fatigue. Such a comprehensive review is necessary to understand the potential of these materials as preventive measures and treatments of exercise fatigue. We expect the findings highlighted and discussed here will help guide the development of new health products and provide a theoretical and scientific basis for future research on exercise fatigue.

Advances in relieving exercise fatigue for curcumin: Molecular targets, bioavailability, and potential mechanism

“…Furthermore, in male rats, the diversity of intestinal microbiota was found to be reduced, the abundance of Helicobacter pylori and Bacteroides showed obvious changes, and the abundance of H. pylori and Bacteroides was significantly enhanced following 4 weeks of excessive swimming training (Yuan et al, 2018). An anti-fatigue mechanism related to gut microbiota can improve the host itself and its metabolites' energy metabolism processes, enhance the intestinal mucosal barrier function, and strengthen the function of the host immune system and other factors (Zhao et al, 2023). Studies have shown that Lactobacillus in the gut of endurance athletes can promote protein utilization and improve branched-chain amino acid content to maintain muscle energy homeostasis, delaying the onset of exercise fatigue (Chen et al, 2016;Jager et al, 2020).…”

“…(De Marchi et al, 2022;Wojcik et al, 2021). The excessive release of pro-inflammatory cytokines can also enhance body fatigue (Zhao et al, 2023). Additionally, intense exercise produces large numbers of metabolites, including blood urea nitrogen (BUN) and lactic acid (LA), which can disrupt the homeostasis of the internal environment and cause fatigue (Ament & Verkerke, 2009;Fathi et al, 2021).…”

“…Simultaneously, acidic metabolites, such as LA, can cause a decrease in muscle pH and inhibit phosphorylase and phosphofructokinase activities, which can have detrimental effects on muscle contraction through glycolysis, enzyme activity, and calcium ion release, resulting in an inadequate supply of energy to the body (Bosca et al, 1985). Finally, excessive exercise also leads to a decrease in adenosine triphosphate (ATP) levels and glycogen content, which reduces muscle contraction capacity (Zhao et al, 2023). The energy deficiency can generate increased permeability or even disintegration of the muscle cell membrane, resulting in the release of creatine kinase (CK) from muscle cells into the bloodstream and thereby increasing the concentration of CK in serum (Fathi et al, 2021;Jing et al, 2017), which enhances physical fatigue.…”