Antioxidative and Energy Metabolism-Improving Effects of Maca Polysaccharide on Cyclophosphamide-Induced Hepatotoxicity Mice via Metabolomic Analysis and Keap1-Nrf2 Pathway

Abstract

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.

Effects of Black Maca supplement on isokinetics muscular performance of elite women’s handball players: placebo-controlled, crossover study

“…Furthermore, as mentioned earlier, BM intake has a positive effect on anti-oxidants, which can improve the 20 m-shuttle run for elite handball athletes. Maca supplements also play a protective role in cyclophosphamide-induced hepatotoxicity, where the Keap1-Nrf2 signaling pathway is regulated to improve oxidative stress, energy metabolism, and restore mitochondrial respiration to prevent liver damage (29). Therefore, for athletes with high-intensity training and competition, including handball, BM intake can have a positive effect on improving their performance by enhancing their cardiopulmonary endurance.…”

Windows Scanning Multiomics: Integrated Metabolomics and Proteomics

“…The affected lipids included LPC 18:3 and 12-HEPE, consistent with reports that CTX led to a decrease in polyunsaturated lysophosphatidylcholines and an increase in oxidized fatty acids. 37,38 Compared with separate extraction, the biomolecules recognized in simultaneous extraction could directly or indirectly establish relationships, reinforcing the idea of correlativity among these biomolecules. Additionally, more amino acids and transfer proteins (Cars, Gars, Qars, Rars, Fars2, Lars, and Acsf3) were identified in the simultaneous extraction, emphasizing the alteration in amino-acid-related metabolism in CTX-induced hepatic damage.…”

An overview of biological functions of natural polysaccharides: influence factors, mitochondria and signaling pathways

“…The intervention of electron transport chain on energy metabolism is inevitable on account of their close relations. Therefore, the de ciency in electron transport chain are capable of worsening ATP synthesis to a great extent [122]. Tong et al measured the activity of complex I and ATP production in two types of colorectal cancer cells after treated with certain concentration of aloe polysaccharide, and the result showed that the activity and intracellular ATP consistently declined, which indicated the treatment account for the inhibition of energy production [15].…”

“…Similar to the previous dimensions for the illustration on the protective effects, polysaccharides also possess certain functions on maintain or increase the activity of electron transport chains, thus disrupt mitochondrial dysfunction. Notably, Fei et al reported the expression of F 0 F 1 -ATPase, which is also known as complex enzyme V located on the mitochondrial membrane, was signi cantly enhanced by the addition of a natural Maca polysaccharide, and thereby reducing hepatotoxicity induced by cyclophosphamide due to better energy metabolism [122]. In another research, the signi cant nding was that a polysaccharide from G. lucidum could recover the reduction in the activity of complex I in ETC resulting from ageing, and therefore enhancing the electron ow from NADH 2 to O 2 [121].…”

“…After the uncoupling of Nrf2 from Keap1, Nrf2 and antioxidant response element (ARE) combine to form a dimer, which triggers a series of antioxidative response encompassing the transcription of detoxifying enzyme, transporter and various antioxidant enzymes such as SOD, CAT, NQO1, and HO-1. An investigation on Maca polysaccharide previously noticed that the mRNA and protein expression levels of Nrf2-Keap1 signaling pathway (Nrf2, HO-1, NQO1) was identically upregulated whereas the expression of Keap1 was correspondingly reduced after addition of polysaccharide, and the treatment distinctly reduced the increase level of malondialdehyde (a symbol of the severity of oxidative stress) induced by cyclophosphamide [122]. Likewise, Yuan et al reported that a polysaccharide isolated from Lycium Barbarum effectively scavenged the accumulated ROS under oxidative stress condition and avoid H2O2treated PC12 cells from apoptosis by increasing the expression of Nrf2 and HO-1 [126].…”