β-Nicotinamide mononucleotide
(Synonyms: 烟酰胺单核苷酸; β-NM; NMN) 目录号 : GC16971
β-烟酰胺单核苷酸是烟酰胺磷酸核糖转移酶（NAMPT）反应的产物，也是关键的NAD+中间体。
Cas No.:1094-61-7
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Hepa1-6 cells |
|
Preparation Method |
β-Nicotinamide mononucleotide was added to the cell medium |
|
Reaction Conditions |
0.5-1 mMβ-Nicotinamide mononucleotide |
|
Applications |
Intracellular NAD + levels were significantly reduced by knocking down or knocking down Nampt or treated with the Nampt inhibitor FK866, whereas NAD + levels were significantly increased by supplementation with NAD + precursors NAM or β-Nicotinamide mononucleotide. |
| Animal experiment [2]: | |
|
Animal models |
Nampt+/- female mice |
|
Preparation Method |
For GTTs, mice were injected with PBS or β-Nicotinamide mononucleotide (500 mg/kg body weight) and fasted for 14 hrs; dextrose (3 g/kg body weight) was then injected intraperitoneally. |
|
Dosage form |
500 mg/kg β-Nicotinamide mononucleotide for 0、15、30、60,120min |
|
Applications |
After β-Nicotinamide mononucleotide administration, there was no difference in blood glucose levels in GTTs between Nampt+/- and control female mice. In addition, β-Nicotinamide mononucleotide-treated Nampt+/- and control mice also had similar plasma insulin levels at each time point. β-Nicotinamide mononucleotide administration corrects the defect in GSIS observed in Nampt+/- mice. |
|
References: [1]: Lv H, Lv G, et,al. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021 Jan 5;33(1):110-127.e5. doi: 10.1016/j.cmet.2020.10.021. Epub 2020 Nov 9. PMID: 33171124. |
|
β-nicotinamide mononucleotide is a product of the nicotinamide phosphoribosyltransferase (NAMPT) reaction and a key NAD+ intermediate. The pharmacological activities of β-nicotinamide mononucleotide include its role in cellular biochemical functions, cardioprotection, diabetes, Alzheimer's disease, and complications associated with obesity[1].
Intracellular NAD + levels were significantly reduced by knocking down or knocking down Nampt or treated with the Nampt inhibitor FK866, whereas NAD + levels were significantly increased by supplementation with NAD + precursors NAM or β-Nicotinamide mononucleotide [3].Treatment of β-nicotinamide mononucleotide, a precursor of NAD+, to HEK293 cells activated and improved the rate of mtDNA replication by increasing nucleotides in mitochondria and decreasing their degradation products: nucleosides. β-Nicotinamide mononucleotide metabolism plays a role in supporting mtDNA replication by maintaining the nucleotide pool balance in the mitochondria[7].
After β-Nicotinamide mononucleotide administration, there was no difference in blood glucose levels in GTTs between Nampt+/- and control female mice. In addition, β-Nicotinamide mononucleotide-treated Nampt+/- and control mice also had similar plasma insulin levels at each time point. β-Nicotinamide mononucleotide administration corrects the defect in GSIS observed in Nampt+/- mice[2]. β-nicotinamide mononucleotide ameliorates glucose intolerance by restoring NAD+ levels in HFD-induced T2D mice. β-nicotinamide mononucleotide also enhances hepatic insulin sensitivity and restores gene expression related to oxidative stress, inflammatory response, and circadian rhythm, partly through SIRT1 activation[4].In a mouse model induced by doxorubicin administered in divided low doses as in the clinics, supplementing mice with a precursor of NAD+ prevented the mtDNA depletion and cardiac dysfunction[5].When investigated whether β-Nicotinamide mononucleotide is superior to nicotinamide (Nam) as a precursor of NAD+ in whole animal experiments. β-Nicotinamide mononucleotide is retained in the body for longer than Nam[6].
References:
[1]: Poddar SK, Sifat AE, et,al. Nicotinamide Mononucleotide: Exploration of Diverse Therapeutic Applications of a Potential Molecule. Biomolecules. 2019 Jan 21;9(1):34. doi: 10.3390/biom9010034. PMID: 30669679; PMCID: PMC6359187.
[2]: Revollo JR, KÖrner A, et,al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007 Nov;6(5):363-75. doi: 10.1016/j.cmet.2007.09.003. PMID: 17983582; PMCID: PMC2098698.
[3]: Lv H, Lv G, et,al. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021 Jan 5;33(1):110-127.e5. doi: 10.1016/j.cmet.2020.10.021. Epub 2020 Nov 9. PMID: 33171124.
[4]:Yoshino J, Mills KF, et,al. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011 Oct 5;14(4):528-36. doi: 10.1016/j.cmet.2011.08.014. PMID: 21982712; PMCID: PMC3204926.
[5]: Li J, Wang PY, et,al. p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities. Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19626-19634. doi: 10.1073/pnas.1904979116. Epub 2019 Sep 5. PMID: 31488712; PMCID: PMC6765288.
[6]: Kawamura T, Mori N, et,al. β-Nicotinamide Mononucleotide, an Anti-Aging Candidate Compound, Is Retained in the Body for Longer than Nicotinamide in Rats. J Nutr Sci Vitaminol (Tokyo). 2016;62(4):272-276. doi: 10.3177/jnsv.62.272. PMID: 27725413.
[7]:Cros C, Margier M, et,al. Nicotinamide Mononucleotide Administration Triggers Macrophages Reprogramming and Alleviates Inflammation During Sepsis Induced by Experimental Peritonitis. Front Mol Biosci. 2022 Jun 27;9:895028. doi: 10.3389/fmolb.2022.895028. PMID: 35832733; PMCID: PMC9271973.
β-烟酰胺单核苷酸是烟酰胺磷酸核糖转移酶（NAMPT）反应的产物,也是关键的NAD+中间体。β-烟酰胺单核苷酸的药理活性包括其在细胞生化功能、心脏保护、糖尿病、阿尔茨海默氏症以及与肥胖相关并发症方面的作用[1]。
通过敲除或抑制Nampt,或使用Nampt抑制剂FK866处理,细胞内NAD+水平显著降低；而通过补充NAD+前体物质NAM或β-烟酰胺单核苷酸,则可以显著增加NAD+水平。将β-烟酰胺单核苷酸作为NAD+的前体物质添加到HEK293细胞中,可以通过增加线粒体中的核苷酸并减少其降解产物（即核苷）来激活和改善mtDNA复制速率。 β-烟酰胺单核苷酸代谢在支持mtDNA复制方面发挥作用,通过保持线粒体中的核苷酸池平衡来实现这一点。
在给β-烟酰胺单核苷酸注射后,Nampt+/-和对照组雌性小鼠的葡萄糖耐量试验中血糖水平没有差异。此外,接受β-烟酰胺单核苷酸治疗的Nampt+/-和对照组小鼠在每个时间点上也具有相似的血浆胰岛素水平。 β- 烟酰胺单核苷酸治疗纠正了观察到的Nampt+/-小 鼠中GSIS缺陷[2]。 β- 烟 酰 胺 单 核 苷 酸 通过恢复HFD诱导T2D小 鼠中NAD + 水平来改善葡萄 糖不耐受性。 β - 烟 酰 胺 单 核 苷 酸 还通过SIRT1激活部分增强肝脏胰岛素敏感性并恢复与氧化应激、炎性反应和昼夜节律相关基因表达[4]。 在以分割低剂量多柔比星诱导的小鼠模型中,用NAD + 前体物质补充可以防止mtDNA消耗和心脏功能障碍[5]。当研究β- 烟 酰 胺 单 核 苷 酸 是否优于烟酰胺（Nam）作为NAD + 前体物质的整体动物实验时,发现β- 烟 酰 胺 单 核 苷 酸在体内的保留时间比Nam长[6]。
| Cas No. | 1094-61-7 | SDF | |
| 别名 | 烟酰胺单核苷酸; β-NM; NMN | ||
| 化学名 | ((2R,3S,4R,5R)-3,4-dihydroxy-5-(3-(hydroxy(imino)methyl)pyridin-1-ium-1-yl)tetrahydrofuran-2-yl)methyl hydrogen phosphate | ||
| Canonical SMILES | N=C(O)C1=C[N+]([C@@]2([H])[C@@](O)([H])[C@@](O)([H])[C@@](O2)([H])COP(O)([O-])=O)=CC=C1 | ||
| 分子式 | C11H15N2O8P | 分子量 | 334.22 |
| 溶解度 | ≥ 33.4mg/mL in Water | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.992 mL | 14.9602 mL | 29.9204 mL |
| 5 mM | 0.5984 mL | 2.992 mL | 5.9841 mL |
| 10 mM | 0.2992 mL | 1.496 mL | 2.992 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
β-nicotinamide mononucleotide (NMN) production in Escherichia coli
Diabetes is a chronic and progressive disease with continuously increasing prevalence, rising financial pressure on the worldwide healthcare systems. Recently, the insulin resistance, hallmark of type 2 diabetes, was cured in mice treated with NAD+ precursor β-nicotinamide mononucleotide (NMN), no toxic effects being reported. However, NMN has a high price tag, more cost effective production methods are needed. This study proposes a biotechnological NMN production method in Escherichia coli. We show that bicistronic expression of recombinant nicotinamide phosphoribosyl transferase (Nampt) and phosphoribosyl pyrophosphate (PRPP) synthetase in the presence of nicotinamide (NAM) and lactose may be a successful strategy for cost effective NMN production. Protein expression vectors carrying NAMPT gene from Haemophilus ducreyi and PRPP synthetase from Bacillus amyloliquefaciens with L135I mutation were transformed in Escherichia coli BL21(DE3)pLysS. NMN production reached a maximum of 15.42 mg per L of bacterial culture (or 17.26 mg per gram of protein) in these cells grown in PYA8 medium supplemented with 0.1% NAM and 1% lactose.
β-Nicotinamide Mononucleotide (NMN) Administrated by Intraperitoneal Injection Mediates Protection Against UVB-Induced Skin Damage in Mice
Objective: Ultraviolet light is an important environmental factor that induces skin oxidation, inflammation, and other diseases. Nicotinamide mononucleotide (NMN) has the effect of anti-oxidation and improving various physiological processes. This study explores the protective effect of NMN monomers given via intraperitoneal injection on UVB-induced photodamage.
Methods: We used a murine model of UVB-induced photodamage to evaluate the effect of an NMN monomer on photoaging skin by assessing skin and liver tissue sections, serum and skin oxidative stress levels, inflammatory markers, mRNA expression, and protein expression of skin- and liver-related genes.
Results: The results showed that NMN treatment blocked UVB-induced photodamage in mice, maintaining normal structure and amount of collagen fibers, normal thickness of epidermis and dermis, reducing the production of mast cells, and maintaining complete organized skin structure. NMN intraperitoneal injection also maintained the normal morphology of the mouse liver after UVB exposure. Meanwhile, NMN intraperitoneal injection was found to increase antioxidant ability and regulate the proinflammatory response of the skin and liver to UVB irradiation by enhancing the activity of antioxidant enzymes, release of anti-inflammatory cytokines, reduction of hydrogen peroxide production (H2O2), and decreased inflammatory cytokines. Furthermore, RT-qPCR results indicated that NMN reduced oxidative stress of skin and liver by promoting the activation of the AMP-activated protein kinase (AMPK) signaling pathway and further increasing the expression of downstream antioxidant genes of AMPK. RT-qPCR results also revealed that NMN treatment could downregulate the mRNA expression of interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, and upregulate NF-kappa-B inhibitor-α (IκB-α) and interleukin (IL)-10 by inhibiting the activation of nuclear factor-κBp65 (NFκB-p65). Finally, NMN upregulated AMPK, IκB-α, SOD1, and CAT in the skin and downregulated NF-κBp65 protein expression, which is in line with the RT-qPCR results.
Conclusion: Based on the above results, NMN monomer treatment with intraperitoneal injection also block the photodamage caused by UVB irradiation in mice by regulating the oxidative stress response and inflammatory response.
Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women
A decrease in the intracellular level of nicotinamide adenine dinucleotide (NAD+), an essential coenzyme for metabolic activity, causes various age-related diseases and metabolic abnormalities. Both in-vivo and in-vitro studies have shown that increasing certain NAD+ levels in cell or tissue by supplementing nicotinamide mononucleotide (NMN), a precursor of NAD+, alleviates age-related diseases and metabolic disorders. In recent years, several clinical trials have been performed to elucidate NMN efficacy in humans. However, previous clinical studies with NMN have not reported on the safety of repeated daily oral administration of ≥ 1000 mg/shot in healthy adult men and women, and human clinical trials on NMN safety are limited. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of 1250 mg of β-NMN administered orally once daily for up to 4 weeks in 31 healthy adult men and women aged 20-65 years. Oral administration of β-NMN did not result in changes exceeding physiological variations in multiple clinical trials, including anthropometry, hematological, biochemical, urine, and body composition analyses. Moreover, no severe adverse events were observed during the study period. Our results indicate that β-NMN is safe and well-tolerated in healthy adult men and women an oral dose of 1250 mg once daily for up to 4 weeks.Trial registration Clinicaltrials.gov Identifier: UMIN000043084. Registered 21/01/2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049188 .
The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial
In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial included 80 middle-aged healthy adults being randomized for a 60-day clinical trial with once daily oral dosing of placebo, 300 mg, 600 mg, or 900 mg NMN. The primary objective was to evaluate blood NAD concentration with dose-dependent regimens. The secondary objectives were to assess the safety and tolerability of NMN supplementation, next to the evaluation of clinical efficacy by measuring physical performance (six-minute walking test), blood biological age (Aging.Ai 3.0 calculator), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and subjective general health assessment [36-Item Short Form Survey Instrument (SF-36)]. Statistical analysis was performed using the Per Protocol analysis with significant level set at p = 0.05. All 80 participants completed the trial without trial protocol violation. Blood NAD concentrations were statistically significantly increased among all NMN-treated groups at day 30 and day 60 when compared to both placebo and baseline (all p ≤ 0.001). Blood NAD concentrations were highest in the groups taking 600 mg and 900 mg NMN. No safety issues, based on monitoring adverse events (AEs), laboratory and clinical measures, were found, and NMN supplementation was well tolerated. Walking distance increase during the six-minute walking test was statistically significantly higher in the 300 mg, 600 mg, and 900 mg groups compared to placebo at both days 30 and 60 (all p < 0.01), with longest walking distances measured in the 600 mg and 900 mg groups. The blood biological age increased significantly in the placebo group and stayed unchanged in all NMN-treated groups at day 60, which resulted in a significant difference between the treated groups and placebo (all p < 0.05). The HOMA-IR showed no statistically significant differences for all NMN-treated groups as compared to placebo at day 60. The change of SF-36 scores at day 30 and day 60 indicated statistically significantly better health of all three treated groups when compared to the placebo group (p < 0.05), except for the SF-36 score change in the 300 mg group at day 30. NMN supplementation increases blood NAD concentrations and is safe and well tolerated with oral dosing up to 900 mg NMN daily. Clinical efficacy expressed by blood NAD concentration and physical performance reaches highest at a dose of 600 mg daily oral intake. This trial was registered with ClinicalTrials.gov, NCT04823260, and Clinical Trial Registry - India, CTRI/2021/03/032421.
Restoring nuclear entry of Sirtuin 2 in oligodendrocyte progenitor cells promotes remyelination during ageing
The age-dependent decline in remyelination potential of the central nervous system during ageing is associated with a declined differentiation capacity of oligodendrocyte progenitor cells (OPCs). The molecular players that can enhance OPC differentiation or rejuvenate OPCs are unclear. Here we show that, in mouse OPCs, nuclear entry of SIRT2 is impaired and NAD+ levels are reduced during ageing. When we supplement β-nicotinamide mononucleotide (β-NMN), an NAD+ precursor, nuclear entry of SIRT2 in OPCs, OPC differentiation, and remyelination were rescued in aged animals. We show that the effects on myelination are mediated via the NAD+-SIRT2-H3K18Ac-ID4 axis, and SIRT2 is required for rejuvenating OPCs. Our results show that SIRT2 and NAD+ levels rescue the aged OPC differentiation potential to levels comparable to young age, providing potential targets to enhance remyelination during ageing.