# 1-methylnicotinamide attenuated inflammation and regulated flora in Necrotizing enterocolitis

**Authors:** Lian Hou, Junbao Du, Jinxin Li, Qing Luo, Quan Kang, Roberto campagna, Roberto campagna, Roberto campagna

PMC · DOI: 10.1371/journal.pone.0324068 · 2025-06-26

## TL;DR

1-MNA reduced inflammation and improved gut health in a rat model of NEC, suggesting it could be a promising treatment for this severe neonatal disease.

## Contribution

This study is the first to demonstrate that 1-MNA can alleviate NEC by modulating inflammation, the TLR4-NF-κB pathway, and gut microbiota.

## Key findings

- 1-MNA reduced mortality and inflammation in NEC rats.
- 1-MNA inhibited the TLR4-NF-κB pathway activation.
- 1-MNA improved intestinal barrier function and modulated gut flora.

## Abstract

Necrotizing enterocolitis(NEC) is a prevalent and destructive illness in neonates. Nicotinamide N-methyltransferase (NNMT) and its derivative, 1-methylnicotinamide (1-MNA), are known to be significant in conditions such as cardiovascular inflammation and renal tubular damage, and 1-MNA has been recognized for its anti-inflammatory effects in various diseases. However, the involvement of NNMT and 1-MNA in the development of NEC remains unclear.

We collected intestinal tissues and blood samples from children with NEC and control subjects for biochemical analysis. The NEC rats were induced by hypoxic cold stimulation and lipopolysaccharide, and control, NEC and NEC + 1-MNA groups were established. Neonatal rats were executed on the fourth day and blood, intestinal and fecal specimens were taken for subsequent testing.

Elevated NNMT and 1-MNA were found in NEC children and NEC rats. Exogenous supplementation of 1-MNA to NEC rats reduced mortality, pathological and inflammatory damage, and inhibited activation of the TLR4-NF-κB pathway in neonatal rats. In addition, 1-MNA improved intestinal barrier function and modulated intestinal flora in NEC rats.

1-MNA attenuated NEC injury by seemingly inhibiting the TLR4-NF-κB pathway, improving intestinal barrier function and modulating intestinal flora. These findings suggest a potential therapeutic role for 1-MNA in NEC management.

## Linked entities

- **Proteins:** TLR4 (toll like receptor 4), NFKB1 (nuclear factor kappa B subunit 1)
- **Chemicals:** 1-methylnicotinamide (PubChem CID 457)
- **Diseases:** Necrotizing enterocolitis (MONDO:0004639)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tlr4 (toll-like receptor 4) [NCBI Gene 29260], Nnmt (nicotinamide N-methyltransferase) [NCBI Gene 300691]
- **Diseases:** Necrotizing enterocolitis (MESH:D020345), cardiovascular inflammation (MESH:D007249), hypoxic (MESH:D002534), diseases (MESH:D004194), renal tubular damage (MESH:D007674)
- **Chemicals:** 1-MNA (MESH:C024058), lipopolysaccharide (MESH:D008070)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12200687/full.md

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Source: https://tomesphere.com/paper/PMC12200687