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Background <p>Alcoholism is a significant contributor to the development of alcoholic liver disease, for which no universally accepted and effective treatment currently exists. A precursor of <b>NAD</b><sup><b>+</b></sup>, β-Nicotinamide mononucleotide (NMN), has revealed potential therapeutic benefits. However, its effectiveness in preventing ethanol-induced liver damage remains uncertain.</p> Methods <p>The objective of this study was to assess the protective effects of NMN and elucidate its potential mechanisms using a mouse model subjected to chronic and binge ethanol feeding. Eight-week-old C57BL/6J mice were randomly assigned to one of four groups (<i>n</i> = 10 per group): control (CTRL), ethanol (EtOH), ethanol with low-dose NMN (EtOH + NMN(L)), and ethanol with high-dose NMN (EtOH + NMN(H)). Following the completion of the experimental protocol, the mice were euthanized at designated time points, and blood, liver, and ileum tissues were collected for analysis of relevant biomarkers.</p> Results <p>Compared to the CTRL group, the EtOH group demonstrated increased liver specific gravity and elevated blood ALT levels. Administration of NMN improved histopathological changes in the liver and ileum of the mice. NMN significantly counteracted the ethanol-induced elevation in liver MDA levels and restored the diminished glutathione (GSH) and superoxide dismutase (SOD) activity levels caused by ethanol exposure. Additionally, NMN inhibited the ethanol-induced expression of cytochrome P450 2E1 (CYP2E1). It also reduced the release of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, which were triggered by ethanol exposure, improved energy homeostasis in the ileum, and reversed the downregulation of mRNA and protein expression of key tight junction proteins in the ileum, specifically ZO-1, Claudin-1, and Occludin, thereby restoring their functional integrity. Furthermore, NMN activated the <b>NAD</b><sup><b>+</b></sup>/ <b>SIRT1</b> signaling pathway, leading to the upregulation of all target genes.</p> Conclusion <p>NMN supplementation provides protection against alcoholic liver injury in a mouse model, potentially through the upregulation of the cellular <b>NAD</b><sup><b>+</b></sup>/ <b>SIRT1</b> pathway. This upregulation enhances antioxidant and anti-inflammatory activities and improves intestinal permeability.</p>

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β-Nicotinamide mononucleotide alleviates Alcohol-Induced liver injury in a mouse model through activation of NAD+/SIRT1 signaling pathways

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月16日

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  • Xinxin Yang,
  • Endian Zheng,
  • Yuxian Lin,
  • Haoyue Sun,
  • Ji Zhang,
  • Yingcong Yu

摘要

Background

Alcoholism is a significant contributor to the development of alcoholic liver disease, for which no universally accepted and effective treatment currently exists. A precursor of NAD+, β-Nicotinamide mononucleotide (NMN), has revealed potential therapeutic benefits. However, its effectiveness in preventing ethanol-induced liver damage remains uncertain.

Methods

The objective of this study was to assess the protective effects of NMN and elucidate its potential mechanisms using a mouse model subjected to chronic and binge ethanol feeding. Eight-week-old C57BL/6J mice were randomly assigned to one of four groups (n = 10 per group): control (CTRL), ethanol (EtOH), ethanol with low-dose NMN (EtOH + NMN(L)), and ethanol with high-dose NMN (EtOH + NMN(H)). Following the completion of the experimental protocol, the mice were euthanized at designated time points, and blood, liver, and ileum tissues were collected for analysis of relevant biomarkers.

Results

Compared to the CTRL group, the EtOH group demonstrated increased liver specific gravity and elevated blood ALT levels. Administration of NMN improved histopathological changes in the liver and ileum of the mice. NMN significantly counteracted the ethanol-induced elevation in liver MDA levels and restored the diminished glutathione (GSH) and superoxide dismutase (SOD) activity levels caused by ethanol exposure. Additionally, NMN inhibited the ethanol-induced expression of cytochrome P450 2E1 (CYP2E1). It also reduced the release of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, which were triggered by ethanol exposure, improved energy homeostasis in the ileum, and reversed the downregulation of mRNA and protein expression of key tight junction proteins in the ileum, specifically ZO-1, Claudin-1, and Occludin, thereby restoring their functional integrity. Furthermore, NMN activated the NAD+/ SIRT1 signaling pathway, leading to the upregulation of all target genes.

Conclusion

NMN supplementation provides protection against alcoholic liver injury in a mouse model, potentially through the upregulation of the cellular NAD+/ SIRT1 pathway. This upregulation enhances antioxidant and anti-inflammatory activities and improves intestinal permeability.