Maca (Lepidium meyenii Walp.) has emerged as a popular functional plant food due to its various pharmacological properties, including anti-oxidation, anti-inflammation and anti-fatigue activity. In this study, we investigated the role of Maca aqueous extract (ME) on muscle during exercise-induced fatigue both in vivo and in vitro. As a result, ME significantly enhanced mouse leg grip-strength and increased exercise endurance in the rota-rod test. ME could clear the accumulation of metabolites – blood lactic acid (BLA), blood urea nitrogen (BUN) and reactive oxygen species (ROS) levels after weight-loaded forced swimming. Focusing on muscle, we found that the administration of ME strengthened mouse muscle structures so that exercise-induced metabolic stress was alleviated by upregulating NAD⁺/NADH. Furthermore, ME inhibited the reduction of the viability and accumulation of ROS by treatment with H₂O₂ in C2C12 skeletal muscle cells. ME-induced activation of energy metabolism in skeletal muscle might up-regulate mitochondrial biogenesis and function, thereby protecting against oxidative stress-induced damage. We concluded that the effects of Maca played a crucial role in the regulation of exercise-induced fatigue in mouse muscle, which could be expected to serve as a functional food supplement for improving exercise performance and alleviating physical fatigue.

Maca compounds prescription (MCP) is a common botanical used in dietary supplements, primarily to treat exercise-induced fatigue. The aim of this study is to elucidate the multi-target mechanism of MCP on fatigue management via network pharmacology and gut microbiota analysis. Databases and literature were used to screen the chemical compounds and targets of MCP. Subsequently, 120 active ingredients and 116 fatigue-related targets played a cooperative role in managing fatigue, where several intestine-specific targets indicated the anti-fatigue mechanism of MCP might be closely related to its prebiotics of intestinal bacteria. Thus, forced swimming tests (FSTs) were carried and mice fecal samples were collected and analyzed by 16S rRNA sequencing. Gut microbiota were beneficially regulated in the MCP-treated group in phylum, genus and OTU levels, respectively, and that with a critical correlation included Lactobacillus and Candidatus Planktophila. The results systematically reveal that MCP acts against fatigue on multi-targets with different ingredients and reshapes the gut microbial ecosystem.

A growing number of nutraceuticals and cosmeceuticals have been utilized for millennia as anti-fatigue supplements in folk medicine. However, the anti-fatigue mechanism underlying is still far from being clearly explained. The aim of the study is to explore the underlying mechanism of the Maca compound preparation (MCP), a prescription for management of exercise-induced fatigue. In this study, mice weight-loaded swimming test was used to evaluate the anti-fatigue effect of MCP. MCP significantly improved the forelimb grip strength and Rota-rod test in behavioral tests via regulating energy metabolism. 16S rDNA sequencing results showed MCP can regulate the intestinal flora at the genus level by increasing several beneficial bacteria (i.e., Lactobacillus, Akkermansia and etc.), and decreasing the harmful bacteria (i.e., Candidatus_Planktophila and Candidatus_Arthromitus), where notable high relevance was observed between the fatigue-related biomarkers and fecal microbiota. The results of microbial function analysis suggested that MCP might improve exercise-induced fatigue by enhancing energy metabolism, carbohydrate and lipid metabolism and metabolism of terpenoids and polyketides and breakdown of amino acid metabolism. In addition, and H₂O₂-induced oxidative stress model on C2C12 cells was employed to further validate the regulation of MCP on energy metabolisms. MCP pre-treatment significantly reduced intracellular ROS accumulation, and increased glycogen content, ATP generation capacity and mitochondrial membrane potential of skeletal muscle cells, as well as conferred anti-cell necrosis ability. In conclusion, MCP plays a key role in regulating fatigue occurrence in exercising and gut microbiota balance, which may be of particular importance in the case of manual workers or sub-healthy populations.

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