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.
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.
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.
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.
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
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.
1. Introduction The NAD precursor nicotinamide mononucleotide (NMN) shows a beneficial effect on ageing, yet excessive NMN accumulation may lead to axon degeneration. How to make the anti-ageing effect of NMN compatible with axonal degeneration caused by NMN accumulation is still a challenge. A preliminary discussion on this issue is conducted in this study. 2. The definition and pathological changes of axonal degeneration Axonal degeneration refers to degenerative changes in the axon as a result of direct damage to the primary or as a result of diseases such as neuronal metabolic disorders, which is a common pathological change of the nervous system. The pathological changes after axonal injury include axonal swelling, fracture, retraction and atrophy. 3. The relationship between NMN and sterile alpha and TIR motif–containing 1 (SARM1) SARM1 is a multi-functional enzyme with base exchange activity, which can cleave nicotinamide adenine dinucleotide (NAD) into adenosine diphosphate ribose (ADPR), cyclic adenosine diphosphate ribose (cADPR) and nicotinamide (NAM). A substantial body of evidence mirrors that the degenerative enzyme SARM1 will be bound to and be activated by NMN. Hence, failed conversion of sufficient NMN into NAD may give rise to toxic NMN accumulation and axon degeneration. 4. The specific pathway of axon degeneration NMN only induces axon degeneration in the presence of SARM1, placing the toxic accumulation on a common pathway of axon death. Notably, nicotinamide mononucleotideadenylyltransferases (NMNATs) has a broader, compartment-specific regulatory role in SARM1 activity. For instance, NMNAT2 depletion is associated with SARM1 activation in axons. In a nutshell, NMNAT2 depletion can give rise to NMN accumulation. Next, NMN binds to and activates the pro-degenerative protein SARM1, leading to rapid NAD consumption and axon degeneration. 5. The impacts of NAD precursors upon axonal health NAD precursors are likely to be safe for most people, but there is a risk for people with compromised NMNAT activity, as these supplements could cause SARM1 activation and neurodegeneration. In healthy individuals, rapid conversion from NMN into NAD can be accomplished by NMNAT2, which is conductive to the prevention of NMN toxic accumulation and maintenance of healthy neurons and axons. Yet, downregulation of NMNAT2 level or activity may result in the upregulation of NMN, thereby leading to SARM1 activation, increased axonal vulnerability and/or axon degeneration. 6. The factors for SARM1 activity SARM1 activity is regulated by a ratio between NMN and NAD. When NMN rises, partial inhibition of SARM1 is only seen at high concentrations of NAD. Inefficient conversion of NMN into NAD because of compromised NMNAT activity is the most likely scenario in which NMN can become toxic. The change in NMN level close to the physiological concentration has a much more significant impact on SARM1 activity than NAD level. A twofold increase in NAD level is not sufficient to delay axon degeneration after injury, and even higher NAD level only temporarily delays axon degeneration. 7. The interaction between SARM1 activation and ageing effect of NMN Sub-lethal/chronic SARM1 activation could increase axonal vulnerability or have a significant impact upon NAD homeostasis and important intracellular signalling pathways in neurons.It is pivotal for life to preserve NAD homeostasis. Maintaining NAD homeostasis could be a viable anti-ageing strategy. Similarly, NMNAT2 depletion increases axon vulnerability and the level of the NMNAT2 is declined with ageing. These findings signify that SARM1 and NMNAT2 may be the key factor to reconcile the axonal degeneration caused by the accumulation of the NAD precursor NMN and ageing effect of NMN. 8. Conclusion Efficient conversion of NMN into NAD is key to preventing SARM1 activation and neurotoxicity. SARM1 and NMNAT2 may be the intersection factors between axon degeneration and anti-ageing therapy. Reference Loreto, Andrea et al. “NMN: The NAD precursor at the intersection between axon degeneration and anti-ageing therapies.” Neuroscience research vol. 197 (2023): 18-24. doi:10.1016/j.neures.2023.01.004 BONTAC NMN product features and advantages * Industrial leading technology: 15 domestic and international NMN patents * Self-owned factories and a number of international certifications to ensure high quality and stable supply of products * NMN raw material supplier of famous David Sinclair team of Harvard University Disclaimer BONTAC shall hold no responsibility for any claims arising directly or indirectly from your reliance on the information and material on this website.