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

Antioxidative and Energy Metabolism-Improving Effects of Maca Polysaccharide on Cyclophosphamide-Induced Hepatotoxicity Mice via Metabolomic Analysis and Keap1-Nrf2 Pathway.
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通过代谢组学分析和 Keap1-Nrf2 通路研究玛卡多糖对环磷酰胺诱导的肝毒性小鼠的抗氧化和能量代谢改善作用

DOI:
10.3390/nu14204264
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发表时间:
2022-10-12
期刊:
影响因子:
5.9
通讯作者:
Wang L
Wang L
中科院分区:
医学2区
文献类型:
--
作者:
Fei W;Zhang J;Yu S;Yue N;Ye D;Zhu Y;Tao R;Chen Y;Chen Y;Li A;Wang L

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大叶独行草玛咖(Maca)作为一种天然食品补充剂,具有很强的抗氧化和改善能量代谢的特性,而玛咖多糖(MP)是其有效成分。在先前的研究中,MP已被证明可以减轻肝脏损伤,环磷酰胺(CYP)引起的肝毒性也是临床实践中的一个主要问题。我们研究了MP对CYP诱导的肝损伤的可能的细胞保护作用,并通过分析由此产生的肝脏代谢谱来探索其潜在的机制。MP可显著抑制血清转氨酶升高,改善病理改变,降低氧化应激,提高能量代谢相关酶水平。代谢组学分析表明,MP纠正了脂质代谢问题,调节了戊糖磷酸途径和酸代谢,从而保护了肝细胞的凋亡。皮尔逊相关分析表明,抗氧化物酶和能量代谢相关酶与这些差异代谢产物密切相关。此外,还探索了Keap1-Nrf2的上游抗氧化信号转导途径,以验证MP保护细胞作用的可能机制。综上所述,MP通过这些潜在的代谢途径在CYP诱导的肝损伤中发挥保护作用,通过调节Keap1-Nrf2信号通路,改善氧化应激,改善能量代谢,恢复线粒体呼吸,从而防止肝损伤。
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.
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