Lepidium meyenii Walp. (Maca), as a natural food supplement, has strong antioxidant and energy metabolism-improving characteristics, and Maca polysaccharide (MP) is its effective component. MP has been shown to mitigate liver damage in previous research, and Cyclophosphamide (CYP)-induced hepatotoxicity is also a major concern in clinical practice. We investigated the possible cytoprotective effect of MP on CYP-induced liver injury, and explored its underlying mechanism by analyzing the resulting liver metabolic profiles. MP significantly inhibited increases in serum transaminase, improved pathological changes, reduced oxidative stress, and increased the levels of energy metabolism-related enzymes. Metabolomic analysis showed that MP corrected lipid metabolic problems and regulated the pentose phosphate pathway and acid metabolism, thereby protecting against apoptosis of hepatocytes. The Pearson correlation analysis indicated that antioxidant enzymes and energy metabolism-related enzymes are closely correlated with these differential metabolites. In addition, the upstream Keap1-Nrf2 antioxidant signal transduction pathway was explored to validate the possible mechanism of the cytoprotective effect of MP. In conclusion, MP plays a protective role in CYP-induced hepatotoxicity through these potential metabolic means, where it ameliorates oxidative stress, improves energy metabolism, and restores mitochondrial respiration by regulating the Keap1-Nrf2 signaling pathway, thereby preventing liver damage.
Keywords: Keap1-Nrf2; antioxidative; cyclophosphamide; energy metabolism; hepatotoxicity; maca polysaccharide; metabolomics.