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.
The main methods of NMNH powder preparation include extraction, fermentation, fortification, biosynthesis and organic matter synthesis. Compared with other preparations, the whole enzyme becomes the mainstream method owing to the advantages of pollution free, high level of purity and
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
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.”.
NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
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.
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.
1. Introduction Nicotinamide adenine dinucleotide (NAD) compartmentalized in adipocytes can modulate adipocyte differentiation and gene expression, in addition to controlling glucose metabolism. White adipose tissue (WAT), one major adipose tissue, may be one of the direct target for NAD supplementation. 2. About WAT In contrast to brown adipose tissue (BAT), WAT contains a single lipid droplet and few mitochondria. WAT, once thought to be morphologically and functionally unremarkable, is in fact highly dynamic, with plasticity and heterogeneity, which is widely distributed in the subcutaneous tissues and around the internal organs. WAT plays a key role in a range of biological processes, such as maintenance of energetic homeostasis, processing and handling of glycans and lipids, blood pressure control, and host defence, with tight relationship with metabolic disorders such as diabetes. 3. The tissue-specific roles of NAD NMN is synthesized from NAM and NR by NAMPT and NRK, respectively. The synthesized NAD+ from NMN is used as a SIRT1 substrate, which leads to the recycling of NAD+ via the salvage pathway. In this process, NAD+ can exert different effects depending on the tissue. Remarkably, NAD precursors can control metabolic stress particularly via focusing on adipose tissue. 4. The effects of boosting NAD+ on WAT Supplementation of NMN and NR has been shown to reduce body weight and enhance insulin sensitivity in regular chow-fed aged wild-type mice and diet-induced obese mice, respectively. NAM supplementation diminishes fat accumulation in diet-induced obese mice. Additionally, both NMN and NR supplementation prevent inflammation even with different treatment duration. NAM administration boosts mitochondrial biogenesis and glutathione synthesis in WAT. Similarly, it is evidenced that NMN treatment in high fat diet-induced type 2 diabetes mouse model facilitates the recovery of Glutathione S-transferase Alpha 2 (Gsta2) gene expression in the liver. 5. The adipose-specific effects of nicotinamide phosphoribosyltransferase (NAMPT) NAMPT, one NAD regulator in WAT, is a promising therapeutic target for the treatment of metabolic disorders. NAMPT plays a potential role in maintaining adipose tissue homoeostasis, as evidenced by the explicitly blocked adipocyte differentiation and lipid synthesis in vitro post treatment of NAMPT inhibitor FK866. For some reasons such as differences in sex, age, and/or basal levels of cellular NAD+ availability, there are various inconclusive results regarding the impacts of NAD+ metabolism on adipocytes in the adipocyte-specific NAMPT-deficient mouse model or in vitro cell models. Further investigation on the effects of NAD+ supplementation and the distinct functions of NAMPT in adipocytes is still needed. 6. Conclusion The importance of NAD metabolism in WAT has been highlighted. NAD has tissue-specific roles. Specifically, WAT may be one of the direct target for NAD supplementation. Supplementation with NAD+ precursors can reduce fat accumulation and inflammation in adipose tissue. Reference Kwon SY, Park YJ. Function of NAD metabolism in white adipose tissue: lessons from mouse models. Adipocyte. 2024;13(1):2313297. doi:10.1080/21623945.2024.2313297 About BONTAC 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 and NR), 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 provide 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.
1.Introduction The senescence in mammals is generally concomitant with the dysregulation of intestinal homeostasis and the accumulation of mitochondrial DNA (mtDNA) mutations. High-burden mtDNA mutations lead to NAD+ depletion and activate the transcription factor ATF5-dependent UPRmt, which in turn promotes and exacerbates the intestinal senescence phenotype. By supplementation with the NAD+ precursor NMN, this intestinal senescence phenotype can be rescued to some extent, as evidenced by the recovery of intestinal organoid differentiation and the increased number of intestinal stem cells. 2. NAD+ depletion during intestinal senescence caused by mtDNA mutations There is impairment of NADH/NAD+ redox in Mut/Mut*** intestines, as manifested by the enriched NADH dehydrogenase complex assembly pathway. Through transfection of intestinal crypt cells with SoNar (a NADH/NAD+ sensor), a higher NADH/NAD+ ratio is observed in Mut/Mut*** mice, hinting the perturbed redox potential. Likewise, following transfection of intestinal crypt cells with FiNad (a NAD+ sensor), less NAD+ content is discovered in the Mut/Mut*** cells. All of these findings mirror NAD+ depletion in the intestinal senescence triggered by mtDNA mutations. Note: mtDNA mutations are classified into four types: negligible (WT/WT), low (WT/WT*), moderate (WT/Mut**) and high (Mut/Mut***). 3. The link between mtDNA mutation content and physiological intestinal senescence The small intestine of aged mouse intestine is characterized by decreased intestinal crypt number, increased villus length, higher expression of CDKN1A/p21 (a well-known senescence marker) and shorter telomere length, which is accompanied by accumulation of mtDNA mutations, primarily low-frequency (less than 0.05) point mutations. 4. LONP1 protein as a candidate marker for intestinal senescence caused by accumulated mtDNA mutations Mitochondrial unfolded protein response (UPRmt) is activated by a variety of mitochondrial stresses, including protein imbalances between mitochondria and the nucleus as well as impaired mitochondrial protein transport. The hallmarks of UPRmt are increased protein expression levels of LONP1, HSP60 and ClpP. Noteworthily, only LONP1 protein is specifically upregulated in senescent UPRmt activation triggered by accumulated mtDNA mutations, which may be a candidate biomarker for intestinal senescence. 5. The role of NAD+ in intestinal senescence induced by elevated mtDNA mutations. NAD+ repletion in vivo alleviates the small intestine senescent phenotypes caused by mtDNA mutation burden, and rescues the decreased colony formation efficiency in Mut/Mut*** intestinal organoids. NAD+-dependent UPRmt triggered by mtDNA mutations regulates intestinal senescence. These data further indicate that NAD+ depletion functions as a key mediator of the intestinal senescence induced by accumulated mtDNA mutations. 6. The role of NAD+ in the signal pathways regulating intestinal senescence caused by increased mtDNA mutations NAD+ repletion rescues the Foxl1 downregulation and Notch1 upregulation in Mut/Mut*** mice, suggesting that mtDNA mutation burden can regulate the function or number of niche cells through NAD+ depletion. In addition, NAD+ depletion caused by increased mtDNA mutation burden induces the decline of LGR5-positive intestinal cells via impairment of the Wnt/β-catenin pathway. 7. Conclusion NAD+ repletion is significant for the regulation of intestinal homeostasis, playing a critical role in rescuing the intestinal senescence phenotype caused by accumulated mtDNA mutations. Reference Yang, Liang et al. “NAD+ dependent UPRmt activation underlies intestinal aging caused by mitochondrial DNA mutations.” Nature communications vol. 15,1 546. 16 Jan. 2024, doi:10.1038/s41467-024-44808-z About BONTAC 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. BONTAC has over 160 domestic and foreign patents, leading the industry of coenzyme and natural products. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and NMN. High quality and stable supply of products can be ensured here. Disclaimer This article is based on the reference in the academic journal. The relevant information is provide 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.