A brief introduction to nmnh manufacturer | BONTAC

A brief introduction to nmnh manufacturer | BONTAC

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. NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. 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. 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.
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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.

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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

BONTAC NMNH product features and advantages

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.”.

NMNH is more potent than NMN

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.  

NADH powder manufacturing method
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BONTAC is a reliable partner that we have been working with for many years. The purity of their coenzyme is very high. Their COA can achieve relatively high test results.

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I discovered BONTAC in 2014 because David's article in cell about NAD and NMN related showed that he used BONTAC's NMN for his experimental material. Then we found them in China. After so many years of cooperation, I think it is a very good company.

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I think green, healthy and high purity are the advantages of BONTAC's products compared with others. I still work with them to this day.

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In 2017, we chose BONTAC's coenzyme, during which our team encountered many technical problems and consulted their technical team, which were able to give us good solutions. Their products are shipped very fast and they work more efficiently.

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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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Further Discussion on the Potential Mechanism of NMN Affecting Neuromuscular Junction

1. Introduction In mammalian cells, the majority of NAD+ is produced from metabolites entering the NAD+ salvage pathway. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme of the salvage pathway, which can convert nicotinamide (NAM) into nicotinamide mononucleotide (NMN). Neuronal NAMPT is important for pre-/post-synaptic NMJ function, and maintaining skeletal muscular function and structure. 2. The involvement of NAMPT in NAD+ salvage pathway NAMPT activity has a pivotal role in energy metabolism and homeostasis. NAMPT can condense nicotinamide (NAM) and 5-phosphoribosyl pyrophosphate (PRPP) into nicotinamide mononucleotide (NMN). NMN is subsequently synthesized into NAD+ by nicotinamide mononucleotide adenylyltransferase (NMNAT), the enzyme immediately after NAMPT. 3. The effect of NMN on partially reversing the NMJ impairments in NAMPT-/- cKO mice In the presence of NMN treatment, vesicle endocytosis/exocytosis is improved and endplate morphology is restored in Thy1-NAMPT-/-conditional knockout (cKO) mice. Also, loss of NAMPT in projection neurons impairs the endocytosis and exocytosis of synaptic vesicles at NMJs, but NMN can largely prevent these impairments. Furthermore, NMN treatment restores sarcomere alignment rather than mitochondrial morphology. 4. The underlying mechanism of NMN affecting NMJs The ameliorating effects of NMN on NMJs may be realized via NAMPT-mediated NAD+ salvage pathway, and this speculation is confirmed by the ameliorated synaptic vesicle cycling, endplate morphology, and muscle fiber structure and function post 2-week administration of the NAD+ precursor, NMN. 5. Conclusion Mechanically, the effects of NMN improving NMJ function, endplate morphology and muscular structure and contractility possibly involves NAMPT-mediated NAD+ salvage pathway. NMN holds a great promise as a therapeutic agent for skeletal muscle diseases. Reference Lundt S, Zhang N, Wang X, Polo-Parada L, Ding S. The effect of NAMPT deletion in projection neurons on the function and structure of neuromuscular junction (NMJ) in mice. Sci Rep. 2020;10(1):99. Published 2020 Jan 9. doi:10.1038/s41598-019-57085-4 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 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.

The Significance of NAD+ in Intestinal Senescence Caused by Elevated mtDNA Mutations

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.

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