Search Results (95)

Background/Objectives: Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD⁺), is used as a dietary supplement, but its safety and metabolic effects in adults remain unclear. This review assessed the short-term safety and tolerability of oral NMN or NMN-related supplementation and examined metabolic and vascular outcomes. Methods: PubMed, Embase, Scopus, Web of Science, CNKI, and Wanfang were searched from inception to 13 May 2026. Eligible studies were parallel randomized controlled trials comparing oral NMN or NMN-related preparations with placebo, blank control, lifestyle control, or the same background intervention without NMN. Safety outcomes included adverse events, serious adverse events, withdrawals due to adverse events, system-specific adverse events, alanine aminotransferase, and aspartate aminotransferase. Random-effects models were used, with GRADE for evidence certainty. Results: Fifteen trials were included, with 10 contributing to safety analyses. NMN doses ranged from 250–2000 mg/day, and durations ranged from 14 days to 24 weeks. NMN did not increase overall, serious, withdrawal-related, or system-specific adverse events, nor did it significantly elevate ALT or AST. No significant effects were observed on body weight, BMI, fasting glucose, HbA1c, lipid profiles, or systolic blood pressure. Diastolic blood pressure decreased slightly, while HOMA-IR showed a non-significant downward trend. Conclusions: Short-term oral NMN or NMN-related supplementation showed favorable tolerability, with no clear increase in adverse events or hepatic biochemical abnormalities. Broad metabolic benefits were not evident, but changes in diastolic blood pressure and HOMA-IR suggest preliminary vascular-metabolic signals, especially in older adults or people with early metabolic risk. Larger and longer trials should confirm efficacy and long-term safety. This review was registered in PROSPERO (CRD420261382497). Full article

This study aimed to evaluate whether the Synerjet system can maximize the transdermal delivery and skin rejuvenation of nano-NMN. In a 4-week split-face trial (n = 21), this combination demonstrated marked clinical superiority over topical nano-NMN alone (p < 0.001), yielding enhanced improvements in wrinkles (with 170.56% relative improvement in periorbital and 154.45% in nasolabial region compared to the control group), pore volume (176.62%), and deep hydration (188.02%). Regarding dermal integrity, the test group showed a 111.56% superior increment in skin elasticity and a 149.75% more effective optimization of melanin intensity relative to the control. Notably, deep-tissue hydration at a 2.5 mm depth demonstrated a 188.02% higher gain, suggesting that the modality significantly fortifies the skin’s physiological moisture reservoir. The test group exhibited a marked improvement over the control across all cutaneous parameters (p < 0.001). Our findings demonstrate that a new combinatorial approach using EP-assisted microjet of a Synerjet system after cold plasma pretreatment and a nano-NMN 10% ampoule resulted in significantly greater improvements in wrinkles, pores, elasticity, pigmentation, and deep skin hydration compared to topical application alone. Consequently, these results demonstrated that the Synerjet system effectively overcame the inherent limitations of nano-delivery technologies, offering a promising modality for advanced cutaneous rejuvenation and a robust framework for future professional dermatological treatments. Full article

Nicotinamide mononucleotide (NMN) plays vital physiological roles as a vitamin B derivative, with nicotinamide riboside kinase (NRK) serving as a key enzyme for its efficient and environmentally friendly synthesis. In this study, semi-rational design was employed to modify the Hi-NRK enzyme at the molecular level, leading to the identification of a critical mutant, Hi-NRK^G8S. This variant exhibited a twofold increase in enzymatic activity and significantly enhanced thermal stability, extending its half-life at 40 °C from 4 to 8 h. By optimizing reaction conditions, NMN yield reached 94.17% at a nicotinamide riboside (NR) substrate concentration of 50 g/L. Further addition of adenylate kinase (ADK) to facilitate ATP recycling increased the yield to 97.24% at 75 g/L NR. This study establishes a foundation for industrial-scale, efficient, and green NMN production. Full article

NAD+ plays crucial roles in various biological processe and its aberrant regulation has been suggested to be critical in the pathogenesis of diverse diseases. Intracellular NAD+ is synthesized largely from nicotinamide mononucleotide (NMN), which is the product of reaction catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Thus, the development of specific inhibitors targeting NAMPT has been suggested as a promising treatment strategy. In this study, we developed a pharmacophore-based QSAR model to discover novel NAMPT inhibitors based on diverse structural features. By virtual screening using the conformation model, we could identify eight novel active analogs having distinct pharmacophores. The biological activity of these candidates on cell viability were further examined. Our study proves the efficiency of our novel screening model and demonstrates its usefulness in the application of drug discovery process. Full article

Deoxynivalenol (DON) is a globally prevalent mycotoxin that threatens food and feed safety via severe multi-organ toxicity. Previous studies indicate that DON induces cellular energy metabolism dysregulation by triggering oxidative stress and impairing mitochondrial function. During this process, nicotinamide adenine dinucleotide (NAD⁺), a central coenzyme in cellular energy metabolism, frequently exhibits significantly decreased intracellular levels or even complete depletion. However, the molecular mechanisms underlying the disruption of NAD⁺ homeostasis by DON exposure, as well as the development of targeted countermeasures, remain elusive. Using human embryonic kidney 293T (HEK293T) cells as an in vitro renal toxicity model, we dissected DON-induced NAD⁺ dysregulation and evaluated the protective potential of nicotinamide (NAM). DON caused significant NAD⁺ depletion in porcine serum (in vivo) and HEK293T cells (in vitro), which was confirmed as a key driver of cytotoxicity. Mechanistically, although DON binds and inhibits nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD⁺ salvage pathway, neither NAMPT knockdown and overexpression nor nicotinamide mononucleotide (NMN) supplementation rescued DON-induced toxicity. Instead, DON dose-dependently activated poly(ADP-ribose) polymerase 1 (PARP1), the primary intracellular NAD⁺-consuming enzyme, to accelerate NAD⁺ depletion. PARP1 knockdown markedly attenuated DON-induced cytotoxicity, identifying PARP1 hyperactivation as the core toxic mechanism. NAM dose-dependently suppressed PARP1 activity, replenished NAD⁺ pools, and reversed cell injury. These findings establish PARP1-driven NAD⁺ depletion as an important mechanism of DON-induced renal toxicity, providing a promising intervention candidate for mitigating DON toxicity in food safety. Full article

The accumulation of oxidative damage and inflammation, induced by internal and external factors, represents a major mechanism underlying the aging of skin. Excessive reactive oxygen species (ROS) trigger mitogen-activated protein kinase (MAPK) pathways, upregulating matrix metalloproteinase (MMP) expression and facilitating extracellular matrix degradation. Although nicotinamide mononucleotide (NMN) and hyaluronic acid (HA) possess antioxidant and dermoprotective properties, their potential combinational effects remain largely obscure. This study evaluated the impact of NMN and HA co-treatment on ROS production, MAPK signaling, MMP-1 secretion, and type I collagen secretion in TNF-α-stimulated human epidermal keratinocytes. ROS levels were assessed via DCFDA assay, while MMP-1 and COL1A1 secretion were quantified using ELISA. Additionally, the regulatory effects on ERK, JNK, and p38 phosphorylation were determined by Western blot. Synergy prediction was analyzed using the SynergyFinder platform via Highest Single Agent and Loewe models. While NMN and HA individually attenuated TNF-α-induced ROS and MMP-1 levels, co-treatment provided superior suppression and exhibited combinational interactions at specific concentrations. These findings suggest that NMN and HA combination treatment effectively modulates oxidative stress and skin-aging-related responses by regulating ROS levels and MAPK signaling pathways. Full article

Background: To evaluate the neuroprotective effect of nicotinamide mononucleotide (NMN), an NAD⁺ precursor, in a D-galactose-induced aging mouse model. Chronic D-galactose administration is widely used to establish age-related cognitive impairment driven by oxidative stress. Methods: Mice received subcutaneous D-galactose for six weeks, concomitantly with oral NMN (300 or 500 mg/kg). Cognitive function was assessed using the Y-maze test and the Elevated Plus Maze test. Oxidative stress indicators, inflammatory cytokines, and Nrf2/HO-1 pathway components were measured by ELISA, Western blotting, and Immunohistochemistry. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results: NMN supplementation improved spatial memory without affecting anxiety-related behavior. NMN enhanced the activities of antioxidant enzymes (SOD, GSH, CAT), reduced malondialdehyde and pro-inflammatory cytokine levels and decreased microglial activation in the hippocampus. Furthermore, NMN remodeled the gut microbiota by increasing butyrate-producing taxa (such as Butyrivibrio_A and Clostridium_T) and activated the Nrf2/HO-1 signaling pathway. Conclusions: NMN alleviates age-related cognitive decline in mice by reducing oxidative stress, suppressing neuroinflammation, and modulating the gut microbiota. Targeting the gut–brain axis and the Nrf2/HO-1 pathway may therefore represent a promising therapeutic strategy for age-related neurodegeneration. Full article

Nicotinamide mononucleotide (NMN), a direct precursor of the essential coenzyme nicotinamide adenine dinucleotide (NAD⁺), confers anti-aging effects and multiple health benefits. Engineered microorganisms represent a promising platform for sustainable industrial production of NMN. Here, the previously reported NMN-producing strain NMN008 was engineered to co-utilize glucose and glycerol for the biosynthesis of NMN from nicotinamide (NAM). First, the glycolytic genes pgi and pykA/pykF were sequentially deleted to disrupt glucose catabolism through the glycolytic pathway, thereby potentially improving precursor availability for NMN biosynthesis. Second, a feedback-resistant glycerol kinase mutant (glpK*) was introduced to enhance glycerol utilization, aiming to compensate for the growth defects associated with impaired glycolysis. These modifications enabled glycerol to primarily support cell growth and energy metabolism, while improving glucose allocation toward NMN biosynthesis by reducing its competitive consumption through glycolysis. As a result, the final strain achieved an NMN titer of 32.92 g/L in a 2 L bioreactor, representing a 26.28% increase in NMN production and a substantial 34.48% improvement in carbon conversion efficiency. Our research provides an effective strategy to achieve industrial-scale production of NMN, laying a foundation for the widespread application of NMN. Full article

Background/Objectives: High blood pressure remains a primary modifiable risk factor for cardiovascular disease. Nicotinamide mononucleotide (NMN) has emerged as a promising supplement; however, its efficacy with respect to blood pressure in humans is unclear. This meta-analysis systematically evaluated the effects of various NMN supplements on resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults with elevated blood pressure. Methods: A systematic literature search was conducted to identify eligible randomized controlled trials (RCTs) using the databases PubMed/MEDLINE, Scopus, Web of Science, and EBSCO from their inception to 13 December 2025. R software was used to combine the data from the included original trials using a common-effects model. Subgroup analyses were performed based on age, baseline body mass index, geographical location, intervention duration, NMN dosage, and baseline blood pressure. Results: A total of 349 participants from 10 RCTs with 11 intervention arms were included. Compared with the placebo, NMN supplementation was associated with a statistically significant but modest reduction in resting DBP (WMD, −2.15 mmHg; 95% CI: −3.68 to −0.61). In contrast, the reduction in resting SBP was not statistically significant. Notably, subgroup analyses revealed that NMN supplementation resulted in a significant reduction in SBP specifically among participants aged 60 years and older (WMD: −3.94 mmHg; 95% CI: −7.06 to −0.82). Conclusions: Our findings provide preliminary and suggestive evidence that NMN supplementation may be associated with a small reduction in resting DBP and a modest beneficial effect on resting SBP in adults aged 60 years and older. However, the potential of NMN as a viable candidate for early-stage blood pressure management requires confirmation through long-term, large-scale, high-quality RCTs in future clinical studies. Full article

Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This study aimed to optimize the HA sheet formulation by evaluating the effects of HA molecular weight and nicotinamide mononucleotide (NMN) loading on therapeutic efficacy. HA sheets were prepared using HA with four different molecular weights (50, 350, 800, and 2000 kDa), and their therapeutic effects were evaluated in an animal oral ulcer model using 6-week-old male Syrian hamsters. Among the formulations tested, the 800 kDa HA sheet exhibited the greatest healing efficacy, and it showed an excellent balance between buccal retention and the sustained release of NMN for the treatment of oral mucositis. In vitro cytotoxicity assays confirmed that HA, with or without NMN, was non-toxic and suitable for local applications. These findings indicate that HA sheets, particularly those composed of 800 kDa HA, may represent a promising and biocompatible mucoadhesive material for the delivery of NMN and the local treatment of oral mucositis associated with head and neck cancer. Full article

This work conducted a transcriptome analysis of canine intestinal epithelial cells (cIECs) treated with nicotinamide mononucleotide (NMN), a physiologically active nucleotide with a pyridine base known for its anti-aging and anti-inflammatory effects. In our experiment, cIECs were cultured and segregated into a control group (Ctrl) and an NMN-treated group. The finding demonstrated that NMN significantly affects cell proliferation in cIECs in comparison to the Ctrl. The transcriptome analysis indicated a high enrichment of genes associated with the cell cycle, proliferation, cellular senescence, and inflammatory pathways in NMN-treated cIECs, showing that NMN has the capacity to modify these biological processes. Compared to the Ctrl group, NMN treatment significantly increased ATP, SOD, CAT and GSH levels and decreased the activities of ROS and MDA. NMN treatment also significantly increased the activity of the relative complex I, III and V enzymes compared to the Ctrl group. Furthermore, the expression of MAPK13, EDN1, TNFAIP6, TNFSF15 and SLC7A11 were decreased significantly, while ACOX2, CPT1C, CCNA1 and CCNE1 were increased significantly in NMN-5μM treatment compared to Ctrl. NMN-treated significantly decreased the expression of Hdac2, Hdac6 and Hdac8, while increasing the expression of Kdm5a, Kdm5b and Kdm5c compared to the Ctrl group. Additionally, ChIP-qPCR use discovered that NMN-treatment significantly downregulated the enrichment of EDN-1 at target loci of NR4A1, SRC1, P300, Pol II and Ser5- Pol II compared to the Ctrl group. Expression of the NR4A1 gene suggests that its exert in biological activities by inhibiting inflammatory responses and anti-aging pathways. Then, we detected the transcriptional activation linked histone markers and found that H3K23ac and H3K27ac were significantly downregulated, while H3K27me3 was significantly upregulated in the NMN-treatment compared to the Ctrl group. We conclude that NMN regulates EDN-1 expression in cIECs through mechanisms involving NR4A1 and histone modifications, highlighting its potential role in canine intestinal health. Full article

Background: The senescence of testicular Leydig cells (LCs) is a key cause of age-related testosterone deficiency, in which oxidative stress (OS) and mitochondrial dysfunction are critical driving mechanisms. We explore whether the bioactive peptide C248 of PRDX4, an intracellular antioxidant, exerts mitochondrial protection to ameliorate LCs’ function. Methods: Based on the antioxidant domains of the PRDX4 protein, small molecular peptides were designed, and bioactive peptide C248 stood out from the crowd. An OS-induced senescence model of LCs was constructed by treating the MLTC-1 cell line with hydrogen peroxide (H₂O₂). C248 peptide or nicotinamide mononucleotide (NMN), as the positive control, was administered in the culture medium. The cellular function-related indicators, including DPPH free radical scavenging rate, cell viability, testosterone level, hydrogen peroxide (H₂O₂) content, senescence-associated β-galactosidase (SA-β-gal) activity, 8-hydroxy-2′-deoxyguanosine (8-OHDG) level, and 4-hydroxynonenal (4-HNE) level, were evaluated. The mitochondrial function and structural indicators, such as mitochondrial membrane potential, ATP production, mitochondrial morphology, and mitochondrial DNA (mtDNA) copy number, were subsequently tested. Results: In vitro experiments confirmed that C248 could scavenge DPPH free radicals in a dose-dependent manner, reduce the levels of reactive oxygen species, and increase antioxidant enzyme activity in LCs (p < 0.01). Both C248 and NMN increased testosterone secretion and improved cell viability (p < 0.01). Both C248 and NMN increased mitochondrial morphology and quantity, mitochondrial membrane potential (p < 0.01), ATP production (p < 0.01), and mitochondrial DNA (mtDNA) copy number (p < 0.01). Conclusion: This study reveals that the small molecular C248, a bioactive peptide of PRDX4, is a new candidate molecule for intervening in LC senescence and confirms that mitochondrial protection is a key strategy for improving age-related testicular dysfunction. Full article

Ultraviolet B (UV-B) radiation significantly contributes to skin photoaging, which is characterized by epidermal thickening, collagen degradation, wrinkle formation, barrier dysfunction, and oxidative stress. Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide, regulates cellular energy metabolism and antioxidant defense and demonstrates anti-aging effects in animal models. Here, we investigated the protective effects of oral NMN supplementation against UV-B-induced photoaging in SKH-1 hairless mice. Over a 10-week experimental period, oral NMN administration significantly alleviated epidermal hypertrophy, reduced wrinkle formation and skin surface roughness, improved hydration and elasticity, and restored transepidermal water loss to near-normal levels. Histological analyses revealed marked preservation of collagen fiber density and attenuation of dermal matrix degradation. Furthermore, NMN supplementation inhibited the phosphorylation of MAPK signaling components (ERK, JNK, and p38), suppressed pro-inflammatory cytokine (TNF-α and IL-6) and matrix-degrading enzyme (MMP-1) expression, and restored hyaluronan synthase (HAS-1 and HAS-2) expression. Additionally, NMN enhanced the systemic antioxidant defense, as indicated by the restored superoxide dismutase activity. Thus, NMN has multi-layered protective effects against UV-B–induced skin aging by modulating oxidative stress, inflammatory signaling, extracellular matrix remodeling, and hyaluronic acid metabolism. Full article

Ferroptosis, a regulated cell death pathway driven by iron-dependent lipid peroxidation, is modulated by cellular antioxidant systems, particularly the glutathione (GSH)–glutathione peroxidase 4 (GPX4) axis. NAD kinase (NADK), the only enzyme converting NAD⁺ to NADP⁺ located in cytoplasm, fuels NADPH-dependent antioxidant defenses. However, its role in ferroptosis regulation remains not fully explored. Using ferroptosis-sensitive HT1080 cells, we employed pharmacological inhibition (thioNAM), siRNA-mediated knockdown, and plasmid-driven overexpression of NADK to dissect its impact on ferroptosis. Complementary interventions with nicotinamide mononucleotide (NMN), glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme 1 (ME1) were used to map metabolic interactions. Cell viability, redox metabolites (NADPH and GSH), oxidative stress markers (ROS, MDA), and protein expression were quantified. ThioNAM depleted NADP(H) and sensitized cells to RSL-3-induced ferroptosis, which was reversible with Ferrostatin-1. NADK knockdown produced similar results, reducing NADP(H) levels and amplifying lipid peroxidation. Conversely, NADK overexpression restored NADPH/GSH levels and rescued ferroptosis. NADK was essential for G6PD- and ME1-mediated NADPH production and ferroptosis resistance. Administration of ThioNAM or knockdown of NADK abolished the ferroptosis-rescuing effects of NMN, whereas NADK overexpression enhanced NMN’s ability to rescue ferroptosis by maintaining redox homeostasis. NADK is a metabolic hub in ferroptosis regulation, bridging NMN-driven NAD⁺ salvage to NADPH synthesis via G6PD/ME1. Targeting NADK offers novel strategies for diseases associated with ferroptosis. Full article

Nicotinamide mononucleotide (NMN), a key precursor of nicotinamide adenine dinucleotide (NAD⁺), plays a central role in cellular energy metabolism. This study investigated the effect of NMN supplementation on boar sperm quality during liquid storage. Semen samples diluted with Modena extender containing 0 to 80 μM NMN were stored at 17 °C for 7 days. Results demonstrate that supplementation with 20 μM NMN significantly improved sperm motility, acrosome integrity, and mitochondrial activity compared with the control group, accompanied by markedly elevated intracellular NAD⁺ and ATP level (p < 0.05). Also, Western blot analysis confirmed the presence of nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3) in boar sperm. Furthermore, sperm treated with 20 μM NMN exhibited a higher level of protein tyrosine phosphorylation and an increased capacitation rate following storage. Tissue explant assays further revealed a significant increase in the number of sperm attached to oviductal epithelial fragments, indicating enhanced sperm–oviduct interactions. The present findings demonstrate that 20 μM NMN supplementation effectively preserves the metabolic activity and functional competence of boar sperm during liquid storage. It provides a promising strategy for improving boar semen preservation. Full article