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
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
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
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
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.
NMN was only considered as a source of cellular energy and an intermediate in NAD+ biosynthesis, currently, the attention of the scientific community has been paid on anti-aging activity and a variety of health benefits and pharmacological activities of NMN which are related to the restoring of NAD+. Thus, NMN has therapeutic effects towards a range of diseases, including age-induced type 2 diabetes, obesity, cerebral and cardiac ischemia, heart failure and cardiomyopathies, Alzheimer’s disease and other neurodegenerative disorders, corneal injury, macular degeneration and retinal degeneration, acute kidney injury and alcoholic liver disease.
1、“Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、Exclusive“Bonpure”seven-step purification technology, high purity(up to 99.9%) and stability of production of NMN powder
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 of NMN powder
5、Multiple in vivo studies show that Bontac NMN powder 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.
NMN powder in general is typically produced via chemical or enzymatic synthesis, or fermentation biosynthesis. There are pros and cons to all three methods.
Chemical synthesis is expensive and labor intensive, and all raw ingredients used are categorized as “unnatural,” i.e., not from biological systems. There are, however, some advantages from the manufacturer’s perspective. The yield is well suited to mass NMN powder production, and all of those unnatural raw ingredients can be carefully controlled. But there are a number of drawbacks as well. Some of the solvents used in the manufacturing process are seriously bad from an environmental standpoint, and impurities and by-products can be challenging to remove from the finished product – that’s seriously bad for the consumer.
Enzymatic production of NMN powder, on the other hand, is considered a “green preparation method.” Like the chemical route, it’s pricey, but it offers a higher yield and impressively high purity. The finished NMN ticks all the boxes – stable, easily absorbed, lightweight, low density, and a low molecular structure.
Fermentation has also been explored as a method of producing NMN, but yield, though high quality, is pretty abysmal, so many supplement companies quite sensibly look to other, more efficacious processes.
Aging, as a natural process is identified by downregulation of energy production in mitochondria of various organs such as brain, adipose tissue, skin, liver, skeletal muscle and pancreas due to the depletion of NAD+ . NAD+ levels in the body decrease as a consequence of increasing NAD+ consuming enzymes when aging There are three different biosynthesis pathways to produce NAD+ in mammalian cells including de novo synthesis from tryptophan, salt and Preiss-Handler pathways. Among these three pathways, NMN is an interproduct by is involved in NAD+ biosynthesis through salt and Preiss-Handler pathways. The salvage pathway is the most efficient and the main route for the NAD+ biosynthesis, in which nicotinamide and 5-phosphoribosyl-1-pyrophosphate are converted to NMN with the enzyme of NAMPT followed by conjugation to ATP and conversion to NAD by NMNAT. Furthermore, NAD+ consuming enzymes are responsible for degradation of NAD+ and consequence nt formation of nicotinamide as a by-product.
The safety of NMN powder cannot be assessed since required clinical and toxicological studies have not been completed yet to establish the recommended safe levels for long term administration. Nevertheless, their safety and efficacy are uncertain and unreliable since most of them have not been back by Rigorous scientific preclinical and clinical testing. This issue has been arisen as manufacturers are hesitant to pay for research and clinical trials due to potential lower profit margin, and there is no authorizing agency to regulate NMN products because it is often product sold as functional food than heavily regulated therapeutic drug. Therefore, more strict approval process has been demanded by consumer advocacy groups requesting regulatory agencies to set standard and restrictions for marketing anti-aging health products, considering safety, health and wellbeing of N red besumers. a panacea for the elderly, because boosting NAD levels when not required may yield some detrimental effects. Therefore, the dose and frequency of NMN supplementation should be carefully prescribed depending on the type of age-related deficiency and all other confronting health conditions of the people. Other NAD precursors over have been studied to diverse age-related deficiencies and they are used for particular deficiencies, only after they are proven for effectiveness and safe to use. Therefore, the same principle should be applied to NMN as well
First, inspect the factory. After some screening, NMN companied 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 NMN 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 NMN cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMN powder produced by Bontac reach the purity of 99.9%. Finally, a professional test spectrum is needed to prove it. Magnetic Resonance Spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). Usually through the analysis of these two spectra, the structure of the compound ca n be preliminarily determined.
Introduction NADH (reduced form of NAD+) serves as a carrier of biological hydrogen and an electron donor, which participates in diverse physiological processes such as protein synthesis, DNA repair, insulin synthesis and secretion, immune response and cell division, playing a critical role in promoting health span and mitigating various disease states. Major enzymatic reactions in substrate metabolism that are dependent upon NAD+/NADH ratio The equilibrium of the NAD+/NADH ratio is vital for maintaining cellular reduction–oxidation (redox) homeostasis and modulating energy metabolism. Several enzymatic reactions in substrate metabolism are carried out in a NAD+/NADH ratio-dependent way. For instance, ketones suppress the increased mitochondrial production of ROS associated with excitotoxic injury by enhancing NADH oxidation (i.e. elevated NAD+/NADH ratio) in the electron transport chain, directly affecting NADH level . NADH in Krebs cycle and glycolysis NADH is produced in glycolysis and the Krebs cycle (also known as citric acid cycle or tricarboxylic acid cycle), which can transfer energy to supply ATP synthesis through the process of oxidative phosphorylation in the inner membrane of the mitochondria. Krebs cycle supplies NADH as an electron carrier to the electron transport chain in mitochondria, while glycolysis-produced NADH can be used by L-lactate dehydrogenase (LDH) or transported to the mitochondria for redox homeostasis. The effects of NADH on the mitochondria are accomplished by specialized shuttle systems (e.g., malate-aspartate or glycerol-3-phosphate). The possible strategies to modulate NADH level The main NAD/NADH biosynthetic pathways include de novo synthesis from tryptophan (TRP), synthesis from either form of vitamin B3, nicotinamide (NAM) or nicotinic acid (NA), or conversion of nicotinamide riboside (NR). Correspondingly, NADH level can be regulated by replenishing NADH precursors (eg. NR and NMN), applying NADH dehydrogenase inhibitors, having diets rich in certain nutrients (eg. vitamin B3), administrating mitochondrial targeting agents and supplementing exogenous NADH. Conclusion NADH may be a versatile therapeutic candidate by leverage of its ability to affect redox homeostasis, mitochondrial functions, and enzymatic reactions. Reference Schiuma G, Lara D, Clement J, Narducci M, Rizzo R. NADH: the redox sensor in aging-related disorders. Antioxid Redox Signal. Published online February 17, 2024. doi:10.1089/ars.2023.0375 BONTAC NADH 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 and over 170 global patents including 8 NADH patents. The purity of BONTAC NADH can reach over 98%. BONTAC NADH has been widely applied in anti-aging health products, diagnostic reagent raw materials, HCY Homocysteine Test Kit, Biomedical R&D, and functional food and beverage. Our products are subjected to strict third-party self-inspection, which are worth of trustworthy. 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.
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.
Introduction The crucial parts of nicotinamide adenine dinucleotide (NAD+) and its metabolites in aging and neurodegeneration have been widely recognized. To spur progress toward biochemical research and interventions targeting aging and neurodegenerative diseases, it is of great significance to accurately quantify NAD+ and its metabolite levels in the NAD+ salvage pathway. Here, a robust and accurate LC-MS/MS method is applied to quantify NAD+ and its metabolites levels in normal and injured mouse sciatic nerve. Limitations of existing methods for quantifying NAD+ and its metabolites Traditional methods for quantifying NAD+ and its metabolites, such as HPLC-UV, NMR, capillary zone electrophoresis, or colorimetric enzymatic assays, face various challenges in sensitivity, selectivity, and indirect measurement. As for existing LC-MS/MS assays for cellular or tissue NAD+ and its metabolites measurements, there are still many difficulties to overcome, such as extended run times, poor chromatographic retention behavior, and unsatisfactory peak shapes. Moreover, only one to three substances in the NAD+ salvage pathway can be covered by these methods. The modifications of LC-MS/MS method On the basis of existing LC-MS/MS assays, the modifications regarding the chromatographic conditions, surrogate matrix and MS/MS conditions are conducted. Specifically, 5 μM of methylene phosphonic acid is employed as the mobile phase additive, which explicitly promotes the signal intensity and peak shape. Given the relatively clean and simple nature of never samples and their small size, ultrapure water is tested as a substitute matrix. Instead of hydrophilic interaction liquid chromatography column and hypercarb column, the Waters Atlantis Premier BEH C18 AX column is utilized, whose unique MaxPeak HPS high-performance surface technology (passivating the column inner wall, eliminating metal surface) enables the high reproducibility, peak symmetry, and baseline separation of all analytes. Besides, MS conditions are optimized to minimize the NAD+ interference signal in the cyclic adenosine diphosphate ribose (cADPR) channel while maintaining the response of cADPR and nicotinamide mononucleotide (NMN), with 4000V for ion spray voltage, 450℃ for turbo heater temperature, 50 psi for Gas 1, 50 psi for Gas 2, 30 psi for curtain gas, and 12 psi for collision gas. Representative chromatogram of nerve samples (normal vs injured) All five analytes achieve baseline separation, where cADPR is a sensitive biomarker in the neurodegeneration model. Herein, sciatic nerve axotomy induces axonal degeneration, leading to reduced NAD+ level and elevated NMN level in the injured nerves, resulting in about a 2-fold increase in the NMN/NAD+ ratio. Simultaneously, the levels of nicotinamide (NAM) and adenosine diphosphate ribose (ADPR), are decreased by about 2-fold, while cADPR level is increased by more than 8-fold. These results are consistent with those of previously reported research, verifying the accuracy of this modified LS-MS/MS method in quantifying NAD+ and its metabolites. Conclusion This modified LC-MS/MS method enables effective baseline separation of NAD+, NMN, NAM, ADPR, and cADPR within a brief runtime of 5 min, which is contributive to early diagnoses of various neurological disorders and drug development for aging and neurodegenerative diseases. Reference Ma Y, Deng L, Du Z. Development and validation of an LC-MS/MS method for quantifying NAD+ and related metabolites in mice sciatic nerves and its application to a nerve injury animal model. J Chromatogr A. doi:10.1016/j.chroma.2024.464821 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. Under no circumstances will BONTAC be held responsible or liable in any way 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.