Nicotinamide Mononucleotide Restores NAD⁺ Levels to Alleviate LPS-Induced Inflammation via the TLR4/NF-κB/MAPK Signaling Pathway in Mice Granulosa Cells.

Ahmed M, Riaz U, Lv H, Amjad M, Ahmed S, Ali S, Ghani MU, Hua G, Yang L

Antioxidants (Basel, Switzerland)31 Dec 2024Cited by 29 (Europe PMC)

PMID39857373PMCIDPMC11762685DOI10.3390/antiox14010039PepBankPUB-39857373

Summary

Inflammation disrupts the normal function of granulosa cells (GCs), which leads to ovarian dysfunction and fertility decline. Inflammatory conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), endometriosis, and age-related ovarian decline are often associated with chronic low-grade inflammation. Nicotinamide mononucleotide (NMN) is an important precursor of NAD⁺ and has gained attention for its potential to modulate cellular metabolism, redox homeostasis, and mitigate inflammation. This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs. The results of this experiment demonstrated that LPS had negative effects on GCs in term of reduced viability and proliferation rates and upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α). Notably, the levels of NAD⁺ and NAD⁺/NADH ratio in GCs were reduced in response to inflammation. On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels. It also enhanced cell viability and proliferation rates of GCs. Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2. NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs. Mechanistically, this study found that NMN suppressed the activation of the TLR4/NF-κB/MAPK signaling pathways in GCs, which regulates inflammatory processes. In conclusion, the findings of this study revealed that NMN has the potential to reduce LPS-mediated inflammatory changes in GCs by modulating NAD⁺ metabolism and inflammatory signaling pathways. NMN supplementation can be used as a potential therapeutic agent for ovarian inflammation and related fertility disorders.

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

Results from this study17

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

01LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN restored NAD levels.
In plain wordsIn cells treated with LPS, NMN restored NAD levels compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseNAD levels
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737301
02LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN restored the NAD/NADH ratio.
In plain wordsIn cells treated with LPS, NMN restored the NAD/NADH ratio compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseNAD/NADH ratio
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737302
03LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced inflammatory IL-1β expression at mRNA and protein levels.
In plain wordsIn cells treated with LPS, NMN reduced IL-1β gene and protein expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseIL-1β expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Inflammation markers · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
2 context sentences(design, population, supporting numbers)
Summary · context
upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α).
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737303
04LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced inflammatory IL-6 expression at mRNA and protein levels.
In plain wordsIn cells treated with LPS, NMN reduced IL-6 gene and protein expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseIL-6 expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Inflammation markers · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
2 context sentences(design, population, supporting numbers)
Summary · context
upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α).
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737304
05LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced inflammatory Cox-2 expression at mRNA and protein levels.
In plain wordsIn cells treated with LPS, NMN reduced Cox-2 gene and protein expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseCox-2 expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Inflammation markers · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
2 context sentences(design, population, supporting numbers)
Summary · context
upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α).
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737305
06LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced inflammatory TNF-α expression at mRNA and protein levels.
In plain wordsIn cells treated with LPS, NMN reduced TNF-α gene and protein expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseTNF-α expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Inflammation markers · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
On the other hand, NMN supplementation restored the NAD⁺ levels and the NAD⁺/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels.
2 context sentences(design, population, supporting numbers)
Summary · context
upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α).
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737306
07LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN enhanced cell viability.
In plain wordsIn cells treated with LPS, NMN improved cell survival compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCell viability
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Cell viability and death · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
It also enhanced cell viability and proliferation rates of GCs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737307
08LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN enhanced proliferation rates.
In plain wordsIn cells treated with LPS, NMN increased cell multiplication compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseCell proliferation
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Cell proliferation and differentiation · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
It also enhanced cell viability and proliferation rates of GCs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737308
09LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced apoptosis rates.
In plain wordsIn cells treated with LPS, NMN reduced programmed cell death compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseApoptosis rate
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Cell viability and death · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737309
10LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced Caspase-3 expression.
In plain wordsIn cells treated with LPS, NMN reduced Caspase-3 expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseCaspase-3 expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737310
11LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced Caspase-9 expression.
In plain wordsIn cells treated with LPS, NMN reduced Caspase-9 expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseCaspase-9 expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737311
12LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced Bax expression.
In plain wordsIn cells treated with LPS, NMN reduced Bax expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseBax expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737312
13LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN increased Bcl-2 expression.
In plain wordsIn cells treated with LPS, NMN increased Bcl-2 expression compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseBcl-2 expression
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737313
14LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN reduced reactive oxygen species.
In plain wordsIn cells treated with LPS, NMN reduced reactive oxygen species compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseReactive oxygen species
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Oxidative stress · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737314
15LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN restored estradiol levels.
In plain wordsIn cells treated with LPS, NMN restored estradiol levels compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseEstradiol levels
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737315
16LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN restored progesterone levels.
In plain wordsIn cells treated with LPS, NMN restored progesterone levels compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseProgesterone levels
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737316
17LabIn vitro (cells)Mechanism
In LPS-treated granulosa cells, NMN suppressed TLR4/NF-κB/MAPK signaling pathway activation.
In plain wordsIn cells treated with LPS, NMN suppressed TLR4/NF-κB/MAPK pathway activation compared with LPS alone.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseTLR4/NF-κB/MAPK pathway activation
Study
mousen: not reported in source
LPS-treated granulosa cells
Comparator
LPS treatment without NMN
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, this study found that NMN suppressed the activation of the TLR4/NF-κB/MAPK signaling pathways in GCs, which regulates inflammatory processes.
1 context sentence(design, population, supporting numbers)
Summary · context
This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs.
Show in the study text Report a problemFND-3985737317

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

Subjects

Terms as the source lists them.

Publication types

Keywords

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