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.
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.
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.
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.
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.
<p>NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.</p>
<p>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</p>
<p>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.</p>
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 Mar 4th is determined as the World Obesity Day. World Obesity Federation, UNICEF and WHO have hosted a global youth-led webinar to talk about obesity & youth. The obesity crisis has gradually attracted much attention. The latest report by the Lancet suggests that one billion people are bothered by obesity (2022), with 650 million adults, 340 million adolescents and 39 million children. Recently, etiological studies and interventions for obesity have been progressively focused on the central nervous system, with an attempt to curb the onset of obesity at its source. Notably, targeting NAD+ salvage pathway in hypothalamic astrocytes may be a potential approach to combat obesity. The association of hypothalamic astrocytes and obesity The hypothalamus functions as the appetite regulation center, which receives and integrates the neuroendocrine factors produced by the central nervous system and peripheral tissues to promote or suppress appetite, so as to affect body weight. Noteworthily, aypothalamic astrocytes can apparently decrease glucose clearance and increase plasma insulin levels, playing an essential role in modulating energy metabolism, which are expected to be a new target for obesity treatment. Alleviation of high-fat diet (HFD)-induced obesity by repressing astrocyte NAD+ salvage pathway Under conditions of excessive fat intake, the NAD+ salvage pathway is specifically activated in hypothalamic astrocytes, which restrains the energy expenditure (EE) and fat oxidation in adipose tissues by downregulating sympathetic nerve innervation, eventually resulting in the accumulation of adipose tissue fat and the development of obesity. CD38 as a downstream mediator of astrocyte inflammation induced by the NAD+ salvage pathway. CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. CD38 knockdown in arcuate nucleus astrocytes diminishes the weight gain, reduces fat mass, increases EE, and lowers RER during HFD consumption. Cd38 depletion in hypothalamic astrocytes may improve hypothalamic inflammation by increasing NAD+ level. Hypothalamic inflammation can not only lead to energy imbalances, but also exacerbate central insulin resistance and leptin resistance, which can lead to the accumulation of fat in peripheral tissues. The role of nicotinamide phosphoribosyltransferase (NAMPT)–NAD+–CD38 axis in obesity In mammals, the salvage pathway represents the primary means of maintaining cellular NAD+ level. A crucial step in the NAD+ salvage pathway is catalyzed by NAMPT. In response to fat overload, the activation of the astrocytic NAMPT-NAD+-CD38 axis induces pro-inflammatory responses in the hypothalamus, eliciting aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes and contribute to the development of obesity. Conclusion Mechanically, inhibition of hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, mitigates hypothalamic inflammation and attenuates the development of HFD-induced obesity in male mice. Reference Park, J.W., Park, S.E., Koh, W. et al (2024). Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity. Nat Commun 15, 2102. https://doi.org/10.1038/s41467-024-46009-0 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. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR). There are various types of NAD to be selected, encompassing NAD ER Grade (endoxin removal), NAD Grade I (IVD/dietary supplement/cosmetics raw powder), NAD Grade II (API/intermediates) and NAD Grade IV (if any higher requirement on the solubility), which can be provided in the form of lyophilized powder or crystalline powder. The purity of BONTAC NAD can reach above 98%. 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. BONTAC holds no responsibility for any claims, damages, losses, expenses or costs resulting or arising directly or indirectly from your reliance on the information and material on this website.
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.