Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?

Wei, Zisong; Chai, H; Chen, Yan; Cheng, Yue; Liu, Xiaojing

doi:10.1016/j.coph.2021.08.006

Cited by 11 publications

(5 citation statements)

References 49 publications

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“…In this model of acute cardiomyopathy, the expression of NAD nicotinamide riboside kinase 2 and NMN was increased, resulting in increased NAD + levels and the amelioration of acute cardiomyopathy ( Diguet et al, 2018 ). Previous reports have also shown that NMN administration activates Sirt1 and restores cardiac function in ischemia–reperfusion models and in aging heart function ( Yamamoto et al, 2014 ; Wei et al, 2021 ).…”

Section: Discussionmentioning

confidence: 84%

Improving lysosomal ferroptosis with NMN administration protects against heart failure

Yagi,

Do,

Hirai

et al. 2023

Life Sci. Alliance

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Myocardial mitochondria are primary sites of myocardial energy metabolism. Mitochondrial disorders are associated with various cardiac diseases. We previously showed that mice with cardiomyocyte-specific knockout of the mitochondrial translation factor p32 developed heart failure from dilated cardiomyopathy. Mitochondrial translation defects cause not only mitochondrial dysfunction but also decreased nicotinamide adenine dinucleotide (NAD+) levels, leading to impaired lysosomal acidification and autophagy. In this study, we investigated whether nicotinamide mononucleotide (NMN) administration, which compensates for decreased NAD+levels, improves heart failure because of mitochondrial dysfunction. NMN administration reduced damaged lysosomes and improved autophagy, thereby reducing heart failure and extending the lifespan in p32cKO mice. We found that lysosomal damage due to mitochondrial dysfunction induced ferroptosis, involving the accumulation of iron in lysosomes and lipid peroxide. The ameliorative effects of NMN supplementation were found to strongly affect lysosomal function rather than mitochondrial function, particularly lysosome-mediated ferroptosis. NMN supplementation can improve lysosomal, rather than mitochondrial, function and prevent chronic heart failure.

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Section: Discussionmentioning

confidence: 84%

Improving lysosomal ferroptosis with NMN administration protects against heart failure

Yagi,

Do,

Hirai

et al. 2023

Life Sci. Alliance

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“…Sepsis results in considerably fluctuating pyridine and adenine nucleotide pools, even depleted ATP reserves, which negatively affect the function of vital organs (Wei et al. 2021 ). Thus, we evaluated whether exogenous NMN could maintain NAD + and ATP levels in lung tissues during endotoxin-induced ALI.…”

Section: Resultsmentioning

confidence: 99%

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

He,

Jiang,

Yang

et al. 2023

Pharmaceutical Biology

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Context Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities. Objective This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro . Materials and methods Cultured 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. Results In 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. Conclusions NMN 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.

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“…Wei et al further refined the TMSOTf-catalyzed condensation reaction by employing niacin ethyl ester and tetraacetylribose as initial materials. NMN was synthesized through four steps of TMSOTf condensation, deacetylation, phosphorylation, and ammonolysis (Figure B), with a total yield of 64% and a purity of β-NMN up to 97% . Recently, a new route utilizing a ketone-reducing reagent to phosphorylate NR was developed .…”

Section: Synthesis Methods Of Nmnmentioning

confidence: 99%

Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System

Cheng,

Li,

et al. 2024

J. Agric. Food Chem.

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Nicotinamide mononucleotide (NMN) has garnered substantial interest as a functional food product. Industrial NMN production relies on chemical methods, facing challenges in separation, purification, and regulatory complexities, leading to elevated prices. In contrast, NMN biosynthesis through fermentation or enzyme catalysis offers notable benefits like eco-friendliness, recyclability, and efficiency, positioning it as a primary avenue for future NMN synthesis. Enzymatic NMN synthesis encompasses the nicotinamide-initial route and nicotinamide ribose-initial routes. Key among these is nicotinamide riboside kinase (NRK), pivotal in the latter route. The NRK-mediated biosynthesis is emerging as a prominent trend due to its streamlined route, simplicity, and precise specificity. The essential aspect is to obtain an engineered NRK that exhibits elevated activity and robust stability. This review comprehensively assesses diverse NMN synthesis methods, offering valuable insights into efficient, sustainable, and economical production routes. It spotlights the emerging NRK-mediated biosynthesis pathway and its significance. The establishment of an adenosine triphosphate (ATP) regeneration system plays a pivotal role in enhancing NMN synthesis efficiency through NRK-catalyzed routes. The review aims to be a reference for researchers developing green and sustainable NMN synthesis, as well as those optimizing NMN production.

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Nicotinamide mononucleotide: An emerging nutraceutical against cardiac aging?

Cited by 11 publications

References 49 publications

Improving lysosomal ferroptosis with NMN administration protects against heart failure

Improving lysosomal ferroptosis with NMN administration protects against heart failure

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

Biosynthesis of Nicotinamide Mononucleotide: Synthesis Method, Enzyme, and Biocatalytic System

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