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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Mechanism for Preventing and Treating Covid-19: NMN VS Paxlovid
With the epidemic control policies loosening worldwide, residents in China, India, Malaysia, Japan and Singapore have suffered a shortage of medicines to varying degrees. But on the other hand, the type of medicines available to the public is dynamically increasing, and at present the anti-Covid-19 stars available on the market include Paxlovid, NMN, etc. What are the similarities and differences between the two in terms of mechanism of preventing and treating the Coronavirus? It is necessary to briefly make out the principle of Covid-19 infection in human cells before discussing the mechanism of action of Paxlovid and NMN. How SARS-CoV-2 infect cells? First, the mature Covid-19 (as shown in Figure 1) is mainly composed of structure proteins including spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein and RNA viral gene. Figure 1. SARS-Cov-2 structure The SARS-CoV-2 opens a channel into the cell by its S protein through recognizing and binding to the ACE2 protein receptor of host cells in vivo. After entering the host cell, the SARS-CoV-2 initiates transcription and translation activities, replicating plenty of SARS-CoV-2, disrupting the cell structure and interfering with the normal cell function. Under this mechanism of action, the supplement of medicine directly comes into play on the sides of spike S protein of the Covid-19 and the ACE2 protein of host cells in human body. Paxlovid prevents the synthesis of S proteins of SARS-CoV-2. The mechanism of Paxlovid to treat Covid-19 Paxlovid was made up with two main ingredients, Nirmatrelvir and Ritonavir. Nirmatrelvir combats SARS-CoV-2 by blocking the synthesis of S proteins.The gene information of all SARS-CoV-2 proteins only take over 1/3 of the right side of RNA strand (as shown in Figure 2), and the remaining 2/3 of the RNA gene strand is used for transcription and translation for multiple proteins to synthesize the polyprotein. After the polyprotein is synthesized, it will be cleaved into several functional proteins likely S protein by virus proteases. Figure 2. RNA structure In short, when the SARS-CoV-2 replicates, the RNA initiates transcription and translation for proteins in bulk and then proteases cleave it to form structural proteins (S protein). The main proteases used when replicating is CL3. Nirmatrelvir of Paxlovid binds to the CL3 protease to prevent the cleavage of the SARS-CoV-2 polyprotein so as to interrupt the protein synthesis of viral. (As shown in Figure 3). What’s more, another ingredient, Ritonavir, works by maintaining the concentration of Nirmatrelvir in the body, prolonging and enhancing its efficacy and maintaining the interruption strength for the replicating protease CL3. Figure 3.CL3 in translation The mechanism of NMN to prevent and treat Covid-19 NMN prevents Covid-19 infection by protecting DNA and reducing ACE2 expression, shutting down the pathway of ACE2 protein into human cells. The researchers found that DNA damages accumulates intracellular ACE2 receptor proteins. However, these two enzymes to repair DNA damage, sirtuins and PARP, need to be to motivated by NAD+. Studies showed that NMN supplementation is effective in increasing NAD+ levels and thus reducing ACE2 protein expression. As it demonstrates that experiment proved that a reduction in ACE2 expression after infected with the SARS-CoV-2, along with a reduction in viral load and tissue damage in the lungs (as shown in Figure 4) based on the situation that 200mg/kg of NMN fed to old mice aged 12 months for 7 days. Figure 4. NMN performance in recuding viral loads The study not only reaffirms the convincing for NMN to treat Covid-19 infection, but based on its proven ability to reduce lung pathological damage and even death in mice infected with neointima, NMN may be used in clinical trials to treat patients with Covid-19 infection. It is clear from the above principles of action that both Paxlovid and NMN work on original source of infection to treat and prevent Covid-19. The difference between the two is that Paxlovid interferes with the replication of the virus while NMN closes the door to the entry of Covid-19 into human cells. Both different mechanisms of action are in principle effective in preventing the invasion of Covid-19. References 1. FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR PAXLOVID, 2022 2. Jin R., Niu C.,et al. DNA damage contributes to age-associated differences in SARS-CoV-2 infection, Aging Cell, 2022
Protective Role of NAD+ Against MI-induced HF in Sprague-Dawley Rats and Beagles
1. Introduction Disrupted nicotinamide adenine dinucleotide (NAD+) metabolism is increasingly deemed to be one of risk factor for amendable cardiovascular disorders. A substantial evidence has mirrored that restoring NAD+ stock and energy metabolism may be effective in alleviating the symptoms of patients with heart failure (HF), one of the typical cardiovascular disease after myocardial infarction (MI). 2. About HF HF has dominant clinical features of ventricular filling or ejection impairment, concomitant with abnormalities in cardiac structure/function. This disorder afflicts about 38 million patients across the world, and the number of HF patients is on the rise with the age, posing a great threat to the life of patients and bringing huge economic burden on the patient family and society. In terms of drug therapies of HF, the "golden triangle" of beta blockers, ACEI/ARB, and aldosterone receptor antagonists has long been the preferred option. Despite significant improvement on the survival of patients, the 5-year mortality rate remains at 50%. Hence, it is of great significance to seek novel way with high efficacy and safety. NAD supplements may be an effective choice for alleviating HF. 3. Research protocol For further verification of the efficacy of NAD+, MI-induced HF models are constructed in male Sprague-Dawley rats and beagles herein. Subsequently, the left anterior descending arteries of MI-induced HF animals are ligated for 1 week, followed by 4-week treatment with or without low/medium/high dose of NAD+ and the positive control drug LCZ696, an angiotensin receptor blocker-neprilysin inhibitor with an cardioprotective effect after MI. 4. The efficacy of NAD on rats and beagles with MI-induced HF NAD+ shows the equivalent efficacy as LCZ696 in the treatment of MI-induced HF, or even better than LCZ696 at the medium and high doses. In rat/beagle HF models, the heart mass index, heart function, and myocardial fibrosis in the infarct marginal zone are dose-dependently improved post administration of NAD or LCZ696, as manifested by decreased end-systolic volume, end-systolic dimension, creatine kinase and lactic dehydrogenase, as well as the increased ejection fractions, fractional shortening, cardiac output, and stroke volume. In addition, the downregulation of left ventricular blood pressure in the HF model animals is ameliorated post administration of NAD or LCZ696. 5. Conclusion In rat and beagle MI-induced HF models, NAD+ conspicuously alleviates myocardial hypertrophy and cardiac function, represses myocardial fibrosis, and reduces the myocardial infarction, laying a theoretical foundation for the clinical application of energy metabolism therapy with NAD+. Reference Pei Z, Yang C, Guo Y, Dong M, Wang F. The Role of NAD+ in Myocardial Ischemia-induced Heart Failure in Sprague-Dawley Rats and Beagles. Curr Pharm Biotechnol. Published online February 13, 2024. doi:10.2174/0113892010275059240103054554 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 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 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.
The Prospect of the NAD+ Precursors in Age-related Diseases
1. Introduction Age-related NAD+ depletion affects physiological functions and contributes to various aging-related diseases. NAD+ precursors can significantly elevate NAD+ level in murine tissues, effectively mitigate metabolic syndrome, enhance cardiovascular health, protect against neurodegeneration, and boost muscular strength, with broad prospect in the anti-aging-related field. 2. The synthesis and metabolism of NAD+ in age-related pathologies NAD+ is synthesized from NAD+ precursors and amino acids tryptophan via three main pathways: De novo, Preiss-Handler, and Salvage. Supplementation of NAD+ precursors can be advantageous in maintaining normal cellular metabolism regulated by NAD+ and NAD+-dependent enzymes such as Sirtuins, PARP, CD38, and SARM1. NAD+ intermediates require conversion into NA to elevate NAD+ level. NAD+ and its metabolism-related enzymes have very important roles in biological processes such as cellular metabolic processes, gene expression, apoptosis and carcinogenesis. NAD+ repletion is drawing attention as an anti-aging intervention. NAD+ precursors, such as NA, NAM, NR, and NMN, provide beneficial effects in various preclinical disease models of age-induced deficits, including metabolic disorders, cardiovascular, neurodegenerative diseases, and musculoskeletal diseases. 3. Comparison on the efficacy of replenishing NAD precursors in pre-clinical studies and clinical studies in age-related pathologies The downregulation of NAD+ level in cells and tissues is not a universal phenomenon for aging-related pathologies. NAD+ merely decreases with age in certain tissues. The efficacy of NAD+ precursors in clinical studies has been limited in comparison with that in the pre-clinical studies. Noteworthily, this issue can be addressed as long as much attention has been paid to the metabolism of NAD. With regards to the oral supplementation of NAD+ precursors, there is obvious link between NAD metabolism and gut microbes. Specifically, oral consumption of NMN is converted into NAMN through interaction with the gut microbiome. In addition, dietary NAM and NR are converted into NA through gut microbiota. 4. Future research directions regarding the NAD+ metabolism It is fundamental to consider how the gut microbiome affects NAD+ metabolism, and changes in microbiome composition may affect the availability of NAD+ precursors. Future studies also require the comparative analysis of different precursors, and the role of gut microbiomes regarding various intermediaries needs to be investigated. Assessment of how NAD+ precursors affect microbiota and how their interaction with NAD+ metabolism benefits the physiological condition is essential for future preclinical and clinical studies. 5. Conclusion Supplementation of suitable NAD+ precursors or intervening in NAD+ metabolism can restore the body's NAD+ level, which is of great practical significance for effectively improving aging-related diseases and prolonging healthy life span is of great practical significance for effectively improving aging-related diseases and prolonging healthy life span. NAD metabolism involves gut microbiome, and in-depth research on their interaction is possibly an important breakthrough in the future to combat aging-related pathologies. Reference Iqbal T, Nakagawa T. The therapeutic perspective of NAD+ precursors in age-related diseases. Biochem Biophys Res Commun. Published online February 2, 2024. doi:10.1016/j.bbrc.2024.149590 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 160 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. BONTAC holds no responsibility for any claims, damages, losses, expenses, costs or liabilities whatsoever resulting or arising directly or indirectly from your reliance on the information and material on this website.