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.
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%) and stability of production of NADH powder
3、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMN powder
4、Provide one-stop product solution customization service
The main methods of NADH powder preparation from worldwide NADH manufacturers 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.
1.Improved energy levels
Not only does NADH act as an important coenzyme in aerobic respiration, the [H] of NADH also carries a large amount of energy. Studies have demonstrated that extracellular use of NADH promotes increased intracellular ATP levels, suggesting that NADH penetrates cell membranes and elevates intracellular energy levels. On a macro level, exogenous supplementation of NADH helps to restore energy and enhance appetite. The increase in energy levels in the brain also helps to improve mental performance and sleep quality. NADH has been used overseas to improve chronic fatigue syndrome, increase exercise endurance, jet lag and other areas.
2.Cellular protection
NADH is a strong antioxidant that naturally occurs in cells and reacts with free radicals to inhibit lipid peroxidation, protecting mitochondrial membranes and mitochondrial function. It has been found that NADH can reduce oxidative stress in cells caused by various factors such as radiation, drugs, toxic substances, strenuous exercise and ischemia, thus protecting vascular endothelial cells, hepatocytes, cardiomyocytes, fibroblasts and neurons. Therefore, injectable or oral NADH is used clinically to improve cardiovascular and cerebrovascular diseases, and as an adjunct to cancer radiotherapy. Topical NADH has been shown to be effective in the treatment of rosacea and contact dermatitis.
3.Promotion of neurotransmitter production
Studies have shown that NADH significantly promotes the production of the neurotransmitter dopamine, a chemical signal that is essential for short-term memory, involuntary movements, muscle tone and spontaneous physical responses. It also mediates the release of growth hormone and determines muscle movement. Without sufficient dopamine, muscles become stiff. Parkinson's disease, for example, is caused in part by a disruption of dopamine synthesis in brain cells. Preliminary clinical data suggest that NADH can help improve the symptoms of Parkinson's disease [9]. NADH also promotes the biosynthesis of norepinephrine and serotonin, showing good potential for use in the relief of depression and Alzheimer's disease.
1. Prevention and treatment of viral-induced inflammatory storms
Scientists have found after extensive research that neo-coronavirus has a mechanism similar to SARS virus to activate inflammatory vesicles NLRP3. and the activation of NLRP3 produces more inflammatory factors, generating excessive inflammation and thus triggering a deadly cytokine storm. This problem can be well addressed by NAD+, which inhibits the activity of NF-κB inflammatory pathway and NLRP3 inflammasome by increasing the activity of sirtuins (SIRT1, SIRT2 and SIRT3), thus preventing cytokine storm caused by excessive inflammation. Therefore, Sinclair and other scientists believe that increasing the concentration of NAD+ may play an important role in the prevention and treatment of neocoronavirus and other viral infections.
2. Restoration of virus-induced metabolic disorders
NAD+ is an essential coenzyme for many cellular energy metabolic pathways, present in every cell of the body, involved in thousands of reactions, and an important player in maintaining cellular viability. In the COVID-19 infection model, NAD+ and NMN supplementation was found to be effective in alleviating cell death and protecting the lung.
The action of supplemental NADH is unclear. Oral NADH supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia. Researchers are also studying the value of NADH supplements for improving mental function in people with Alzheimer's disease, and minimizing physical disability and relieving depression in people with Parkinson's disease. Some healthy individuals also take NADH supplements orally to improve concentration and memory capacity, as well as to increase athletic endurance. However, to date there have been no published studies to indicate that using NADH is in any way effective or safe for these purposes
First, inspect the factory. After some screening, NADH 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 NADH 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 NADH 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.
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 Solute carrier family 25 member 51 (SLC25A51) is perceived as a mammalian transporter, which is capable of importing oxidized nicotinamide adenine dinucleotide (NAD+) into mitochondrial matrix. Remarkably, upregulation of SLC25A51 has correlation with poorer outcomes in patients with acute myeloid leukemia (AML), a clinically aggressive haematological disease with a mortality rate of over 70% within the first 5 years following an initial diagnosis. The association between NAD+/NADH ratio and SLC25A51 in AML cells Both NAD+ (oxidative form) and NADH (reduced form) are essential coenzymes for cellular energy metabolism, and the ratio of NAD+/NADH reflects the metabolic activity and health state, which has a direct impact on cellular rhythms, senescence, carcinogenesis and death. Importing mitochondrial NAD+ by SLC25A51 could be a critical aspect supporting mitochondrial metabolism in AML tumorigenesis. Concretely, the decreased mitochondrial NAD+/NADH ratio and specific loss of reduced ubiquinol are observed post the depletion of SLC25A51 in AML cells U937. SLC25A51 as an NAD+/NADH redox decoupler in AML SLC25A51 functions as an NAD+/NADH redox decoupler in AML tumorigenesis to sustain an oxidative TCA cycle and promote glutaminolysis. Depletion of SLC25A51 results in increased usage of non-glutamine carbon sources to support the TCA cycle, as determined by increased proportions of unlabeled TCA intermediates. SLC25A51 is required for robust glutaminolysis. In the context of SLC25A51 depletion, AML cells are forced to rely more on glutamine for aspartate synthesis. Alleviation of AML by SLC25A51 depletion and 5-azacytidine Loss of SLC25A51 leads to a subcellular redistribution of NAD+ in AML cells to limit proliferation. The combination of SLC25A51 depletion and 5-azacytidine is much effective in repressing the viability of AML cells and prolonging the survival time of mice. Conclusion SLC25A51 can maintain mitochondrial oxidative phosphorylation and boost the proliferation of AML cells by regulating NAD+/NADH ratio in mitochondria, with promising efficacy in treating AML, especially in combination with 5-azacytidine. 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.
Introduction Myocardial ischemia-reperfusion (I/R) injury has emerged as an urgent clinical issue that may offset the benefits of reperfusion therapy and even worsen the prognosis of acute myocardial infarction, a severe cardiovascular disease with significant mortality and morbidity. Nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) intermediate, has been unveiled to hold great therapeutic potential in myocardial I/R injury. About myocardial I/R injury Myocardial I/R injury refers to the damaging effects on cardiomyocytes or heart tissues following ischemia and the regaining of blood perfusion or oxygen supply, with characteristics of cell swelling, contracture of myofibrils, and disruption of the sarcolemma in myocardium. The mechanisms of myocardial I/R injury are extremely complex, chiefly involving cellular and molecular biological events such as cellular oxidative stress, intracellular calcium overload, mitochondrial dysfunction, inflammatory response, apoptosis and autophagy. Strikingly, autophagy and oxidative stress have been perceived as vital factors in the treatment of myocardial I/R injury. The alleviating effects of NR on myocardial I/R injury in mice NR can improve the cardiac function of mice with myocardial I/R injury, and reduce the generation of myocardial injury- and oxidative stress-associated biomarkers. Herein, the optimal concentration of NR for protection against H/R injury is 10 mM. In vivo, NR diminishes the area of myocardial ischemic infarction, alleviates pathological myocardial changes, decreases inflammatory cell infiltration, and attenuates the levels of mitochondrial reactive oxygen species (ROS) as well as creatine kinase myocardial band (CK-MB). In vitro, NR pretreatment lessens the levels of lactate dehydrogenase, CK-MB, malondialdehyde, superoxide dismutase and ROS, as well as the mortality of H9c2 cells after the induction of hypoxia/reoxygenation (H/R) injury. The significance of Sirt 1 pathway in the regulation of autophagy by NR Excessive autophagy can exacerbate I/R injury, giving rise to an increase in cardiomyocyte apoptosis and greater cardiac dysfunction. Noteworthily, NR can lead to the activation of Sirt 1, an NAD+-dependent enzyme, to protect the H9c2 cells against excessive autophagy, thereby alleviating the myocardial I/R injury. Post NR pre-treatment, the levels of autophagy-related proteins (Beclin 1, P62 and LC3II/LC3I) are apparently downregulated in the H9c2 cells challenged with H/R. Remarkably, the supplement of Sirt 1 inhibitor EX527 overtly attenuates NR-induced reduction in the expression levels of autophagy-related proteins under H/R conditions, hinting the significance of Sirt 1 in the regulation of autophagy by NR. Conclusion The myocardial I/R injury can be ameliorated by regulating the autophagy and oxidative stress with NR. On the one hand, NR can directly participate in oxidative reduction to lessen the level of oxidative stress in cardiomyocytes. On the other hand, NR can protect cardiomyocytes against excessive autophagy, which is possibly accomplished by increasing the NAD+ content in the body via the Sirt 1 pathway. Reference Yuan C, Yang H, Lan W, et al. Nicotinamide ribose ameliorates myocardial ischemia/reperfusion injury by regulating autophagy and regulating oxidative stress. Exp Ther Med. 2024;27(5):187. doi:10.3892/etm.2024.12475 BONTAC NR BONTAC is one of the few suppliers in China that can launch mass production of raw materials for NR, with self-owned factory and professional R&D team. Up till now, there are 173 BONTAC patents. BONTAC provides one-stop service for customized products. Both malate and chloride salt forms of NR are available. By dirt of unique Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method, the product content and conversion rate can be maintained in a higher level. The purity of BONTAC NR can reach above 97%. 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.