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.
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.”.
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.
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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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The latest research proves: Coenzyme NAD+ can enhance tumor immunity! Expert Comment from Chinese Academy of Sciences
On August 10, 2021, researchers from Shanghai University of Science and Technology published an article titled NAD+ supplement potentiates tumor killing function by rescuing defective TUBBY-mediated NAMPT transcription in tumor infiltrated T cells in Cell Reports, revealing that NAD+ in supplemented during CAR-T therapy and immune checkpoint inhibitor therapy, it can improve the anti-tumor activity of T. At present, the supplementary precursor of NAD+, as a nutritional product,has been verified for human consumption safety.This achievement provides a simply and feasible new method for improving the anti-tumor activity of T cells. Cancer immunotherapies including the adoptive transfer of naturally occurring tumor-infiltrating lymphocytes (TILs) and genetically engineered T cells, as well as the use of immune checkpoint blockade (ICB) to boost the function of T cells, have emerged as promising approaches to achieve durable clinical responses of otherwise treatment-refractory cancers (Lee et al., 2015; Rosenberg and Restifo, 2015; Sharma and Allison, 2015). Although immunotherapies have been successfully used in the clinic, the number of patients benefiting from them is still limited (Fradet et al., 2019; Newick et al., 2017). Tumor microenvironment (TME)-related immunosuppression has emerged as the major reason for low and/or no response to both immunotherapies (Ninomiya et al., 2015; Schoenfeld and Hellmann, 2020). Therefore, efforts to investigate and overcome TME-related limitations in immune therapies are of great urgency. The fact that immune cells and cancer cells share many fundamental metabolic pathways implies an irreconcilable competition for nutrients in TME (Andrejeva and Rathmell, 2017; Chang et al., 2015). During uncontrolled proliferation, cancer cells hijack alternative pathways for more rapid metabolite generation (Vander Heiden et al., 2009). As a consequence, nutrient depletion, hypoxia, acidity, and generation of metabolites that can be toxic in the TME may hinder successful immunotherapy (Weinberg et al., 2010). Indeed, TILs often experience mitochondrial stress within growing tumors and become exhausted (Scharping et al., 2016). Interestingly, multiple studies also indicate that metabolic changes in TME could re-shape T cell differentiation and functional activity (Bailis et al., 2019; Chang et al., 2013; Peng et al., 2016). All these evidences inspired us to hypothesize that metabolic reprogramming in T cells might rescue them from a stressed metabolic environment, thereby reinvigorating their anti-tumor activity (Buck et al., 2016; Zhang et al., 2017). In this current study, by integrating both genetic and chemical screens, we identified that NAMPT, a key gene involved in NAD+ biosynthesis, was essential for T cell activation. NAMPT inhibition led to robust NAD+ decline in T cells, thereby disrupting glycolysis regulation and mitochondrial function, blocking ATP synthesis, and dampening the T cell receptor (TCR) downstream signaling cascade. Building on the observation that TILs have relatively lower NAD+ and NAMPT expression levels than T cells from peripheral blood mononuclear cells (PBMCs) in ovarian cancer patients, we performed genetic screening in T cells and identified that Tubby (TUB) is a transcription factor for NAMPT. Finally, we applied this basic knowledge in the (pre) clinic and showed very strong evidence that supplementation with NAD+ dramatically improves the anti-tumor killing activity both in adoptively transferred CAR-T cells therapy and immune check point blockade therapy, indicating their promising potential for targeting NAD+ metabolism to better treat cancers. 1.NAD+ regulates the activation of T cells by affecting energy metabolism After antigen stimulation, T cells undergo metabolic reprogramming, from mitochondrial oxidation to glycolysis as the main source of ATP. While maintaining sufficient mitochondrial functions to support cell proliferation and effector functions.Given that NAD+ is the main coenzyme for redox, the researchers verified the effect of NAD+ on the level of metabolism in T cells through experiments such as metabolic mass spectrometry and isotope labeling. The results of in vitro experiments show that NAD+ deficiency will significantly reduce the level of glycolysis, TCA cycle and electron transport chain metabolism in T cells. Through the experiment of replenishing ATP, the researchers found that the lack of NAD+ mainly inhibits the production of ATP in T cells, thereby reducing the level of T cell activation. 2.The NAD+ salvage synthesis pathway regulated by NAMPT is essential for T cell activation The metabolic reprogramming process regulates the activation and differentiation of immune cells. Targeting T cell metabolism provides an opportunity to modulate the immune response in a cellular way. Immune cells in the tumor microenvironment, their own metabolic level will also be correspondingly affected. The researchers in this article have discovered the important role of NAMPT in the activation of T cells through genome-wide sgRNA screening and metabolism-related small molecule inhibitor screening experiments. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions and can be synthesized through the salvage pathway, de novo synthesis pathway, and Preiss-Handler pathway. The NAMPT metabolic enzyme is mainly involved in the NAD+ salvage synthesis pathway. Analysis of clinical tumor samples found that in tumor-infiltrating T cells, their NAD+ levels and NAMPT levels were lower than other T cells. Researchers speculate that NAD+ levels may be one of the factors that affect the anti-tumor activity of tumor-infiltrating T cells. 3.Supplement NAD+ to enhance the anti-tumor activity of T cells Immunotherapy has been exploratory research in cancer treatment, but the main problem is the best treatment strategy and the effectiveness of immunotherapy in the overall population. Researchers want to study whether enhancing the activation ability of T cells by supplementing NAD+ levels can enhance the effect of T cell-based immunotherapy. At the same time, in the anti-CD19 CAR-T therapy model and anti-PD-1 immune checkpoint inhibitor therapy model, it was verified that supplementation of NAD+ significantly enhanced the tumor-killing effect of T cells. The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while the CAR-T treatment group without NAD+ supplemented only about 20 % Of mice achieved tumor clearance. Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors are relatively tolerant to anti-PD-1 treatment, and the inhibitory effect is not significant. However, the growth of B16F10 tumors in the anti-PD-1 and NAD+ treatment group could be significantly inhibited. Based on this, NAD+ supplementation can enhance the anti-tumor effect of T cell-based immunotherapy. 4.How to supplement NAD+ The NAD+ molecule is large and cannot be directly absorbed and utilized by the human body. The NAD+ directly ingested orally is mainly hydrolyzed by brush border cells in the small intestine. In terms of thinking, there is indeed another way to supplement NAD+, which is to find a way to supplement a certain substance so that it can synthesize NAD+ autonomously in the human body. There are three ways to synthesize NAD+ in the human body: Preiss-Handler pathway, de novo synthesis pathway and salvage synthesis pathway. Although the three ways can synthesize NAD+, there is also a primary and secondary distinction. Among them, the NAD+ produced by the first two synthetic pathways only accounts for about 15% of the total human NAD+, and the remaining 85% is achieved through the way of remedial synthesis. In other words, the salvage synthesis pathway is the key to the human body to supplement NAD+. Among the precursors of NAD+, nicotinamide (NAM), NMN and nicotinamide ribose (NR) all synthesize NAD+ through a salvage synthesis pathway, so these three substances have become the body's choice for supplementing NAD+. Although NR itself has no side effects, in the process of NAD+ synthesis, most of it is not directly converted into NMN, but needs to be digested into NAM first, and then participate in the synthesis of NMN, which still cannot escape the limitation of rate-limiting enzymes. Therefore, the ability to supplement NAD+ through oral administration of NR is also limited . As a precursor for supplementing NAD+, NMN not only bypasses the restriction of rate-limiting enzymes, but is also absorbed very quickly in the body and can be directly converted into NAD+. Therefore, it can be used as a direct, rapid and effective method to supplement NAD+. Expert Reviews: Xu Chenqi (Excellence and Innovation Center of Molecular Cell Science, Chinese Academy of Sciences, Immunology Research Expert) Cancer treatment is a problem in the world. The development of immunotherapy has made up for the limitations of traditional cancer treatment and expanded the treatment methods of doctors. Cancer immunotherapy can be divided into immune checkpoint blocking therapy, engineered T cell therapy, tumor vaccine, etc. These treatment methods have played a certain role in the clinical treatment of cancer. At the same time, this also makes the current focus of immunotherapy research on how to further enhance the effect of immunotherapy and expand the beneficiaries of immunotherapy.
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.
Looking for Your Arrival at Booth No 6.1 S17 in the 89th CMEF
On April 11th~14th 2024, the 89th China International Medical Equipment Fair (CMEF) is going to be held at National Exhibition and Convention Center in Shanghai. Here is a feast of medicine and in vitro diagnosis. BONTAC sincerely invites you to visit Booth No. 6.1 S17 in the 89th CMEF. Our patent-grade coenzyme raw materials for IVD reagents will be there. Waiting for your arrival! About the 89th CMEF Founded in 1979, CMEF is held twice a year in spring and autumn. After more than 40 years of innovation and development, it has become the world's leading medical and health technology platform integrating scientific and technological innovation, new product debut, business matchmaking and brand dissemination, academic exchanges, trend insights, education and training, etc. CMEF 2024 is themed by " New Tech, Smart Future", involving tens of thousands of products, technologies and solutions for medical imaging, in vitro diagnostics, medical consumables, orthopedic medical robots, etc. BONTAC profile Bontac Bio-Engineering (Shenzhen) Co., Ltd. (also referred to as BONTAC) is a high-tech enterprise established in July 2012, with self-owned factories and more than 170 invention patents. BONTAC integrates R&D, production and sales. There are six major series of product in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates. By virtue of the first whole-enzyme catalysis technology in China, BONTAC takes the industry lead in its niche field of coenzyme. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields.