Advantages of NMNH
NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity（up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
Advantages of NADH
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
Advantages of NAD
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
Advantages of MNM
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity（up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
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Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
BONTAC NMNH product features and advantages
1、“Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder.
2、Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability.
3、Exclusive “Bonpure” seven-step purification technology, high purity（up to 99%) and stability of production of NMNH powder
4、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder
5、Provide one-stop product solution customization service
NADH powder manufacturing method
The main methods of NMNH powder preparation include extraction, fermentation, fortification, biosynthesis and organic matter synthesis. Compared with other preparations, the whole enzyme become the mainstream method owing to the advantages of pollution free, high level of purity and stability.
NMNH is more potent than NMN
when applied to cultured cells, the NMNH is shown to be more efficient than NMN as it was able to “significantly increase NAD+ at a ten times lower concentration (5 µM) than that needed for NMN”. Moreover, NMNH shows to be more effective, as at 500 µM concentration, it achieved “an almost 10- fold increase in the NAD+ concentration, while NMN was only able to double NAD+ content in these cells, even at 1 mM concentration.”.
Interestingly, NMNH also appears to act quicker and has a longer-lasting effect compared to NMN. According to the authors, NMNH induces a “significant increase in NAD+ levels within 15 minutes”, and “NAD+ steadily increased for up to 6 hours and remained stable for 24 hours, while NMN reached its plateau after only 1 hour, most likely because the NMN recycling pathways to NAD+ had already become saturated.”.
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NMNH also proved more effective than NMN in raising NAD+ levels in a variety of tissues when administered at the same concentration, confirming the results observed in cell lines. The data presented in this study also corroborate the evidence that NAD+ boosters protect against different models of acute kidney injury, and place NMNH as a great alternative intervention to other NAD+ precursors to reduce tubular damage and accelerate recovery.
To overcome the limitations of the current repertoire of NAD+ enhancers, other molecules with a more pronounced effect on the NAD+ intracellular pool are desired. This has stimulated us to investigate the use of the reduced form of nicotinamide mononucleotide (NMNH) as an NAD+ enhancer. There is very scarce information about the role of this molecule in cells. In fact, only one enzymatic activity has been described to produce NMNH. This is the NADH diphosphatase activity of the human peroxisomal Nudix hydrolase hNUDT1232 and the murine mitochondrial Nudt13.33 It has been postulated that, in cells, NMNH would be converted to NADH via nicotinamide mononucleotide adenylyl transferases (NMNATs).34 However, both NMNH production by Nudix diphosphatases and its use by NMNATs for NADH synthesis have only been described in vitro using isolated proteins, and how NMNH participates in cellular NAD+ metabolism remains unknown.
First, inspect the factory. After some screening, NMNH companies that directly face consumers pay more attention to brand building. Therefore, for a good brand, quality is the most important thing, and the first thing to control the quality of raw materials is to inspect the factory. Bontac company actually manufacturing NMNH powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NMN powder. If high purity NMNH cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMNH powder produced by Bontac reach the purity of 99%. Finally, a professional test spectrum is needed to prove it. Common methods for determining the structure of an organic compound include Nuclear Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound can be preliminarily determined.
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An Integrated Map of Molecular Mechanisms Underlying the Effect of NMN in T2DM
Introduction Diabetes is one of the dominant causes of death and disability worldwide, greatly affecting the life quality of patients. According to the latest data on diabetes released by the Lancet (GBD Study 2021), type 2 diabetes mellitus (T2DM) cases almost makes up 96.0% of all diabetes cases, with the hallmark of impaired glucose uptake. There are approximately 529 million patients with diabetes in 2021, with age-standardized prevalence of 6.1%. Remarkably, β-nicotinamide mononucleotide (NMN) is able to ameliorate T2DM via unexpected effects on adipose tissue rather than mitochondrial biogenesis. Global age-standardised prevalence of type 1 and type 2 diabetes from 1990 through 2050 forecasts Risk factors for T2DM High body mass index (BMI) is the main risk factor for T2DM, followed by dietary risk factors, environmental or occupational factors, smoking, insufficient physical activity, alcohol consumption, etc. The organ-specific effects of NMN treatment in T2DM NMN alleviates the mildly impaired and energy-inefficient protein synthesis in mice with T2DM induced by high-fat food. Specifically, NMN downregulates spliceosome proteins while upregulating ribosome proteins in hepatocytes. Besides, NMN downregulates proteasome and upregulates DNA replication and cell cycle pathways in muscle cells. Integrated proteomics data analysis of NMN-treated HFD mouse liver. Integrated proteomics data analysis of mouse muscle tissue. Adipose tissue, an energy reservoir, has been attested to be implicated with glucose metabolism. NMN boosts glucose uptake via Resistin downregulation, increased protein synthesis/degradation, fatty acid degradation, lysosome protein upregulation (most notably upregulation of the ATP6V1 proton pump), mTOR cell proliferation signaling in white adipose tissue, differentiation of preadipocytes to brown adipose cells and/or overexpression of thermogenic UCP1, a protein of the inner mitochondrial membrane of brown adipose tissue. Integrated proteomics data analysis of NMN-treated HFD mouse adipose tissue Conclusion NMN exerts organ-specific effects, with a vital role in improving glucose uptake, showing potent potential in the management of metabolic disorders including T2DM. Reference [1] GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203-234. doi:10.1016/S0140-6736(23)01301-6 [2] Popescu RG, Dinischiotu A, Soare T, Vlase E, Marinescu GC. Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis. Int J Mol Sci. 2024;25(5):2594. Published 2024 Feb 23. doi:10.3390/ijms25052594 BONTAC NMN BONTAC is the pioneer of NMN industry and the first manufacturer to launch NMN mass production, with the first whole-enzyme catalysis technology around the world. At present, BONTAC has become the leading enterprise in niche areas of coenzyme products. Notably, BONTAC is the NMN raw material supplier of famous David Sinclair team at the Harvard University, who uses the raw materials of BONTAC in a paper titled “Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging”. Our services and products have been highly recognized by global partners. Furthermore, BONTAC has the first national and the only provincial independent coenzyme engineering technology research center in Guangdong, China. The coenzyme products of BOMNTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.
Targeting NAD+ Salvage Pathway as a Potential Approach to Combat Obesity
Introduction Mar 4th is determined as the World Obesity Day. World Obesity Federation, UNICEF and WHO have hosted a global youth-led webinar to talk about obesity & youth. The obesity crisis has gradually attracted much attention. The latest report by the Lancet suggests that one billion people are bothered by obesity (2022), with 650 million adults, 340 million adolescents and 39 million children. Recently, etiological studies and interventions for obesity have been progressively focused on the central nervous system, with an attempt to curb the onset of obesity at its source. Notably, targeting NAD+ salvage pathway in hypothalamic astrocytes may be a potential approach to combat obesity. The association of hypothalamic astrocytes and obesity The hypothalamus functions as the appetite regulation center, which receives and integrates the neuroendocrine factors produced by the central nervous system and peripheral tissues to promote or suppress appetite, so as to affect body weight. Noteworthily, aypothalamic astrocytes can apparently decrease glucose clearance and increase plasma insulin levels, playing an essential role in modulating energy metabolism, which are expected to be a new target for obesity treatment. Alleviation of high-fat diet (HFD)-induced obesity by repressing astrocyte NAD+ salvage pathway Under conditions of excessive fat intake, the NAD+ salvage pathway is specifically activated in hypothalamic astrocytes, which restrains the energy expenditure (EE) and fat oxidation in adipose tissues by downregulating sympathetic nerve innervation, eventually resulting in the accumulation of adipose tissue fat and the development of obesity. CD38 as a downstream mediator of astrocyte inflammation induced by the NAD+ salvage pathway. CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. CD38 knockdown in arcuate nucleus astrocytes diminishes the weight gain, reduces fat mass, increases EE, and lowers RER during HFD consumption. Cd38 depletion in hypothalamic astrocytes may improve hypothalamic inflammation by increasing NAD+ level. Hypothalamic inflammation can not only lead to energy imbalances, but also exacerbate central insulin resistance and leptin resistance, which can lead to the accumulation of fat in peripheral tissues. The role of nicotinamide phosphoribosyltransferase (NAMPT)–NAD+–CD38 axis in obesity In mammals, the salvage pathway represents the primary means of maintaining cellular NAD+ level. A crucial step in the NAD+ salvage pathway is catalyzed by NAMPT. In response to fat overload, the activation of the astrocytic NAMPT-NAD+-CD38 axis induces pro-inflammatory responses in the hypothalamus, eliciting aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes and contribute to the development of obesity. Conclusion Mechanically, inhibition of hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, mitigates hypothalamic inflammation and attenuates the development of HFD-induced obesity in male mice. Reference Park, J.W., Park, S.E., Koh, W. et al (2024). Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity. Nat Commun 15, 2102. https://doi.org/10.1038/s41467-024-46009-0 BONTAC NAD BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR). There are various types of NAD to be selected, encompassing NAD ER Grade (endoxin removal), NAD Grade I (IVD/dietary supplement/cosmetics raw powder), NAD Grade II (API/intermediates) and NAD Grade IV (if any higher requirement on the solubility), which can be provided in the form of lyophilized powder or crystalline powder. The purity of BONTAC NAD can reach above 98%. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. BONTAC holds no responsibility for any claims, damages, losses, expenses or costs resulting or arising directly or indirectly from your reliance on the information and material on this website.
The Molecular Mechanisms Underlying the Interaction Between NAD+/NMN and DBC1
Introduction Oxidized form of nicotinamide adenine dinucleotide (NAD+) and its precursor nicotinamide mononucleotide (NMN) have been uncovered to restore DNA repair and prevent cancer progression via the deleted in breast cancer 1 (DBC1). This research is committed to deciphering the detailed molecular mechanisms. About DBC1 DBC1 is a nuclear protein initially cloned from a human chromosome 8p21 region, which can modulate diversified targets by protein-protein interaction, contributing to various cellular processes such as apoptosis, DNA repair, senescence, transcription, metabolism, circadian cycle, epigenetic regulation, cell proliferation, and tumorigenesis. The affinity and molecular binding mechanisms between NAD+/NMN and DBC1354–396 Under the help of nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments, it is verified that both NAD+ and NMN have a binding relationship with the NHD domain of DBC1. Specifically, NAD+ interacts with DBC1354-396 through hydrogen bonds, with a binding affinity (8.99 μM) nearly twice that of NMN (17.0 μM) and the key binding sites are primarily residues E363 and D372. The vital roles of E363 and D372 mutagenesis in ligand-protein interaction The N-terminal loop of DBC1354-396 encloses the small ligand within a local space, anchoring NAD+ and NMN to the protein through key amino acid residues E363 and D372 via hydrogen bonding. Conclusion Both NAD+ and its precursor NMN can bind to DBC1's NHD domain (DBC1354–396) at key sites E363 and D372, providing novel clues for the development of targeted therapies and drug research on DBC1-associated disease including tumors. Reference Ou L, Zhao X, Wu IJ, et al. Molecular mechanism of NAD+ and NMN binding to the Nudix homology domains of DBC1. Int J Biol Macromol. Published online February 12, 2024. doi:10.1016/j.ijbiomac.2024.130131 BONTAC NAD BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team consisting of Doctors and Masters. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN), with various forms to be selected (eg. endoxin-free IVD-grade NAD, Na-free or Na-containing NAD; NR-CL or NR-Malate). High quality and stable supply of products can be better ensured here with the exclusive Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method. Disclaimer This article is based on the reference in the academic journal. The relevant information is provided for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. Under no circumstances will BONTAC be held responsible or liable in any way for any claims, damages, losses, expenses, costs or liabilities whatsoever (including, without limitation, any direct or indirect damages for loss of profits, business interruption or loss of information) resulting or arising directly or indirectly from your reliance on the information and material on this website.