Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway.

He S, Jiang X, Yang J, Wu Y, Shi J, Wu X, Du S, Zhang Y, Gong L, Dong S, Yu J

Pharmaceutical biology15 Dec 2023Cited by 46 (Europe PMC)

PMID38100537PMCIDPMC10732210DOI10.1080/13880209.2023.2292256PepBankPUB-38100537

Summary

ContextSepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities.ObjectiveThis study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro.Materials and methodsCultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 μg/mL) and NMN (500 μM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD⁺ and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected.ResultsIn MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization.ConclusionsNMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

11 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In septic mice, NMN improved lung pathology.
In plain wordsIn mice with sepsis, NMN reduced lung damage.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseLung pathology
Study
mousen: not reported in source
LPS-induced sepsis
Outcome group
Inflammation markers · Respiratory
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527.
Show in the study text Report a problemFND-3810053702
02AnimalAnimal study (in vivo)Mechanism
In septic mice, NMN reduced the lung W/D ratio.
In plain wordsIn mice with sepsis, NMN reduced the lung wet-to-dry weight ratio.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseLung W/D ratio
Study
mousen: not reported in source
LPS-induced sepsis
Outcome group
Inflammation markers · Respiratory
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527.
Show in the study text Report a problemFND-3810053703
03AnimalAnimal study (in vivo)Mechanism
In septic mice, NMN reduced MPO activity.
In plain wordsIn mice with sepsis, NMN reduced MPO activity.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseMPO activity
Study
mousen: not reported in source
LPS-induced sepsis
Outcome group
Inflammation markers · Respiratory
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527.
Show in the study text Report a problemFND-3810053704
04AnimalAnimal study (in vivo)Mechanism
In septic mice, NMN increased NAD+ levels.
In plain wordsIn mice with sepsis, NMN increased NAD+ levels.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseNAD+ levels
Study
mousen: not reported in source
LPS-induced sepsis
Outcome group
Inflammation markers · Respiratory
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527.
Show in the study text Report a problemFND-3810053705
05AnimalAnimal study (in vivo)Mechanism
In septic mice, NMN increased ATP levels.
In plain wordsIn mice with sepsis, NMN increased ATP levels.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseATP levels
Study
mousen: not reported in source
LPS-induced sepsis
Outcome group
Inflammation markers · Respiratory
Studied dose
500 mg/kg · intraperitonealAs given in this study (mouse).
Source sentences
Summary
In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD⁺ and ATP levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527.
Show in the study text Report a problemFND-3810053706
06AnimalOther designMechanism
In sepsis-induced ALI models, NMN suppressed M1 macrophage polarization.
In plain wordsIn animal and cell lung injury models, NMN reduced M1 macrophage polarization.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseM1 polarization
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation.
1 context sentence(design, population, supporting numbers)
Summary · context
Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI.
Show in the study text Report a problemFND-3810053707
07AnimalOther designMechanism
In sepsis-induced ALI models, NMN promoted M2 macrophage polarization.
In plain wordsIn animal and cell lung injury models, NMN increased M2 macrophage polarization.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseM2 polarization
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation.
1 context sentence(design, population, supporting numbers)
Summary · context
Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI.
Show in the study text Report a problemFND-3810053708
08AnimalOther designMechanism
In sepsis-induced ALI models, NMN increased SIRT1 expression.
In plain wordsIn animal and cell lung injury models, NMN increased SIRT1 expression.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSIRT1 expression
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation.
1 context sentence(design, population, supporting numbers)
Summary · context
Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI.
Show in the study text Report a problemFND-3810053709
09AnimalOther designMechanism
In sepsis-induced ALI models, NMN inhibited NF-κB-p65 acetylation.
In plain wordsIn animal and cell lung injury models, NMN reduced NF-κB-p65 acetylation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseNF-κB-p65 acetylation
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation.
1 context sentence(design, population, supporting numbers)
Summary · context
Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI.
Show in the study text Report a problemFND-3810053710
10AnimalOther designMechanism
In sepsis-induced ALI models, NMN inhibited NF-κB-p65 phosphorylation.
In plain wordsIn animal and cell lung injury models, NMN reduced NF-κB-p65 phosphorylation.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseNF-κB-p65 phosphorylation
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation.
1 context sentence(design, population, supporting numbers)
Summary · context
Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI.
Show in the study text Report a problemFND-3810053711
11LabIn vitro (cells)Mechanism
In MH-S cells, NMN decreased the apoptotic rate from 12.25% to 5.74%.
In plain wordsIn cells, NMN reduced the rate of cell death from 12.25% to 5.74%.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseApoptotic rate
Study
n: not reported in source
LPS-stimulated MH-S cells
Comparator
LPS without NMN
Outcome group
Inflammation markers · Respiratory
Studied dose
500 μM · 12 hAs given in this study.
Measurements
Apoptotic rate
12.25%
LPS
Apoptotic rate
5.74%
LPS + NMN
Source sentences
Summary
In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%.
1 context sentence(design, population, supporting numbers)
Summary · context
MH-S cells were stimulated with LPS (1 μg/mL) and NMN (500 μM) for 12 h grouping as control, LPS, and LPS + NMN.
Show in the study text Report a problemFND-3810053701

Studies that did not test the peptide alone1

In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking NMN (nicotinamide mononucleotide).

12AnimalNot a test of NMN (nicotinamide mononucleotide) aloneOther designMechanism
In ALI models, SIRT1 inhibition reversed NMN-induced M2 macrophage polarization.
In plain wordsIn animal and cell lung injury models, SIRT1 inhibition reversed NMN-induced M2 macrophage polarization.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
Not applicableSIRT1 dependence of M2 polarization
Study
n: not reported in source
Outcome group
Inflammation markers · Respiratory
Source sentences
Summary
Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization.
In this study, NMN (nicotinamide mononucleotide) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking NMN (nicotinamide mononucleotide).
Show in the study text Report a problemFND-3810053712

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

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