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Nicotinamide riboside Sale

(Synonyms: 烟酰胺核糖) 目录号 : GC44401

烟酰胺核苷是维生素 B3 和 NAD+ 前体的一种形式,通过烟酰胺核苷激酶 (NRK) 和 NMNAT,或通过核苷磷酸化酶和 NAM 补救作用,转化为生物可利用的 NAD+.在体外实验中,烟酰胺核苷通过激活 SirT1/PGC-1α/线粒体生物合成途径减轻酒精引起的肝损伤。

Nicotinamide riboside Chemical Structure

Cas No.:1341-23-7

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实验参考方法

Cell experiment [1]:

Cell lines

Murine RAW 264.7 macrophages

Preparation Method

The prepared mouse bone marrow-derived macrophages were cultured and stored at 37°C in 5% CO2. Murine RAW 264.7 macrophages were treated with EtOH (80 mM), MeCHO (200 μM), and nicotinamide riboside (1 mM), respectively, and ROS accumulation was determined.

Reaction Conditions

1 mM ,72 h

Applications

Ethanol and its metabolite, acetaldehyde, significantly increased cellular ROS levels, but Nicotinamide riboside completely abolished the increase to a basal level in RAW 264.7 macrophages.

Animal experiment [2]:

Animal models

Eight-week-old male C57BL/6 J mice

Preparation Method

The reared mice were randomly divided into 3 groups: control group (CTRL), ethanol group (EtOH) and nicotinamide riboside supplementation group (EtOH+ Nicotinamide riboside ). Mice in the ethanol and nicotinamide riboside supplemented groups were fed a Lieber-DeCarli ethanol liquid diet, while control mice were paired as previously described.

Dosage form

400 mg/kg, oral gavage once daily for 10 consecutive days

Applications

Mice were fed in pairs and there was no difference in body weight between the three groups. Fat accumulation was observed in the ethanol group, while only a few tiny lipid droplets were observed in the nicotinamide riboside group. Nicotinamide riboside significantly decreased serum ALT and AST and liver triglyceride levels, and slightly decreased liver weight ratio.

References:

[1]. Wang S, Wan T,et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol. 2018 Jul;17:89-98.

[2]. Kang H, Park YK, Lee JY. Nicotinamide riboside, an NAD+ precursor, attenuates inflammation and oxidative stress by activating sirtuin 1 in alcohol-stimulated macrophages. Lab Invest. 2021 Sep;101(9):1225-1237.

产品描述

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, is converted to bioavailable NAD+, via nicotinamide riboside kinase (NRK) and NMNAT, or by the action of nucleoside phosphorylase and NAM salvage[1-2].

In in vitro experiments ,nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway [3]. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans[4].

Nicotinamide Riboside was able to enhance the skeletal muscle NAD+ metabolome, inducing gene expression signatures implicated in downregulation of energy metabolism pathways, but did not affect muscle mitochondrial bioenergetics or metabolism[5]. Nicotinamide Riboside enhances deacetylase activity in vivo, deacetylates PGC-1α in muscle, liver, and BAT, and it induces deacetylase activity in tissues where NAD+ accumulates[6].

References:
[1] Bieganowski P., Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell.2004;117:495–502.
[2] Nikiforov A., Dolle C., Niere M. Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation. J. Biol. Chem. 2011;286:21767–21778.
[3] Wang S, Wan T, et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol. 2018 Jul;17:89-98.
[4] Nascimento EBM, Moonen MPB, et al. Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans. J Clin Endocrinol Metab. 2021 Apr 23;106(5):1437-1447.
[5] Elhassan YS, Kluckova K, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019 Aug 13;28(7):1717-1728.e6.
[6] Cantó C, Houtkooper RH,et al. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012 Jun 6;15(6):838-47.

烟酰胺核苷是维生素 B3 和 NAD+ 前体的一种形式,通过烟酰胺核苷激酶 (NRK) 和 NMNAT,或通过核苷磷酸化酶和 NAM 补救作用,转化为生物可利用的 NAD+[1-2].

在体外实验中,烟酰胺核苷通过激活 SirT1/PGC-1α/线粒体生物合成途径减轻酒精引起的肝损伤[3]。烟酰胺核苷增强人体体外 β-肾上腺素能棕色脂肪组织活性[4]

烟酰胺核苷能够增强骨骼肌 NAD+ 代谢组,诱导与能量代谢途径下调有关的基因表达特征,但不影响肌肉线粒体生物能量学或代谢[5]。烟酰胺核苷在体内增强脱乙酰酶活性,使肌肉、肝脏和BAT中的PGC-1α脱乙酰化,并在NAD+积累的组织中诱导脱乙酰酶活性[6]

Chemical Properties

Cas No. 1341-23-7 SDF
别名 烟酰胺核糖
Canonical SMILES NC(C1=C[N+]([C@H]2[C@H](O)[C@H](O)[C@@H](CO)O2)=CC=C1)=O
分子式 C11H15N2O5 分子量 255.3
溶解度 Soluble in Water 储存条件 Store at -20°C
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1 mM 3.917 mL 19.5848 mL 39.1696 mL
5 mM 0.7834 mL 3.917 mL 7.8339 mL
10 mM 0.3917 mL 1.9585 mL 3.917 mL
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Research Update

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses

Nutrients 2020 May 31;12(6):1616.PMID:32486488DOI:10.3390/nu12061616.

Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.

Can Nicotinamide riboside protect against cognitive impairment?

Curr Opin Clin Nutr Metab Care 2020 Nov;23(6):413-420.PMID:32925178DOI:10.1097/MCO.0000000000000691.

Purpose of review: The present review aims to address the clinical benefits of using Nicotinamide riboside, a precursor to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+) as a therapeutic agent to attenuate age-related cognitive decline. Recent findings: Oral supplementation with Nicotinamide riboside can inhibit the accumulation of pathological hallmarks of Alzheimer's disease and improve learning and memory in various murine models for dementia. Nicotinamide riboside can also reduce DNA damage, neuroinflammation, apoptosis, and improved hippocampal synaptic plasticity in diabetic mice, and another Alzheimer's disease mouse model. The cognitive benefits of Nicotinamide riboside in Alzheimer's disease models may be modulated in part by upregulation of proliferator-activated-γ coactivator 1α-mediated β-secretase 1(BACE-1) ubiquitination and degradation, preventing Aβ production in the brain. Nicotinamide riboside also maintained blood-brain barrier integrity and maintained the gut microbiota in a mouse model for cerebral small vessel disease and alcohol-induced depression, respectively. Oral Nicotinamide riboside has been shown to be bioavailable and well tolerated in humans with limited adverse effects compared to other NAD+ precursors. Summary: Oral Nicotinamide riboside may represent a promising stratagem to improve cognitive decline during 'normal' ageing, Alzheimer's disease and other diseases. Results from recent clinical trials are needed to enumerate the preclinical benefits in humans.

The NADPARK study: A randomized phase I trial of Nicotinamide riboside supplementation in Parkinson's disease

Cell Metab 2022 Mar 1;34(3):396-407.e6.PMID:35235774DOI:10.1016/j.cmet.2022.02.001.

We conducted a double-blinded phase I clinical trial to establish whether nicotinamide adenine dinucleotide (NAD) replenishment therapy, via oral intake of Nicotinamide riboside (NR), is safe, augments cerebral NAD levels, and impacts cerebral metabolism in Parkinson's disease (PD). Thirty newly diagnosed, treatment-naive patients received 1,000 mg NR or placebo for 30 days. NR treatment was well tolerated and led to a significant, but variable, increase in cerebral NAD levels-measured by 31phosphorous magnetic resonance spectroscopy-and related metabolites in the cerebrospinal fluid. NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography, and this was associated with mild clinical improvement. NR augmented the NAD metabolome and induced transcriptional upregulation of processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle. Furthermore, NR decreased the levels of inflammatory cytokines in serum and cerebrospinal fluid. Our findings nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.

The NAD(+) precursor Nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

Cell Metab 2012 Jun 6;15(6):838-47.PMID:22682224DOI:10.1016/j.cmet.2012.04.022.

As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of Nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function.

Chronic Nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults

Nat Commun 2018 Mar 29;9(1):1286.PMID:29599478DOI:10.1038/s41467-018-03421-7.

Nicotinamide adenine dinucleotide (NAD+) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD+ precursors to augment NAD+ bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD+ precursor vitamin, Nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group.