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
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.”.
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 becomes the mainstream method owing to the advantages of pollution free, high level of purity and
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Frequently Asked Question
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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.
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
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
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.
Bontac in Boao Health Food Science Conference & Expo（FHE）
Bontac in Boao Health Food Science Conference & Expo（FHE） From 22 to 25 February 2023, the Boao Health Food Science Conference and Expo was successfully held at the permanent venue of the Boao Forum for Asia in Hainan, China. This international conference build an international platform for exchange and cooperation among government, academia, industry, and industry, academia and research, which aims to promote the development of the health food industry through the exchange of scientific information at home and abroad. Bontac performace in FHE The conference gathered several prominent scientists including 10 academicians, over 200 experts and scholars, and invited many popular food enterprises likely Nestle, Pepsi from the United States, Europe, Japan, Australia, New Zealand and other countries. More importantly, exhibition featured a number of high-tech companies that focus on high-tech development of the production of nutritious and healthy food products. As one of the high-tech companies attending the exhibition, Bontac, which has obtained over 160 international patents and is committed to the design of new biosynthetic pathways to explore and mass-produce natural products for food ingredients, was invited to attend the conference and companies vital stake holders to deliver academic views on the technological innovation and healthy development of the food industry. Figure 1: Xinhua Officical Record for Bontac in FHE Bontac Products in FHE Expo Bontac main products starring NMN, rare ginsenosides, NAD, NADH and NADPH were all present at booth C34 in FHE Expo. And that booth C34 attracted lots of exhibitors to consult who communicated with each other upon appearance owing to the obvious striking advantages likely Bontac manufacture technology of whole coenzyme, sustainable supply chain, complete quality system and environment-protection and energy-saving preparation. What’s more, the academician of the Chinese Academy of Engineering and Chairman of FHE, Chen Junshi also visited Bontac booth and highly commend on the Bontac performance and demonstration. Figure 2: Chen Visited Bontac Booth in FHE Bontac recognizes the importance of the upstream of raw material side in biotechnology as the key to product innovation. On the other hand, with the increasingly demand for high-quality food, synthetic biotechnology stands on the point of the potential to provide consumers with greener and healthier food ingredients. Therefore, as far as Bontac is concerned, developing and shaping innovative technology ownership supports to effectively solving the problem of insufficient plant and animal extracts, reducing the environmental burden, and contributing to carbon neutrality and human sustainable development. At present, Bontac has already launched industrialized stevioside and rare ginsenoside which can be utilized in the field of health food. In future, Bontac will set up more product lines for more raw materials with higher purity and better quality as health food ingredients. Bontac honor time in FHE It was great honor for Bontac to win innovative product enterprise award, which identified Bontac long-term commitment to the exploration and innovation of synthetic biology and health technology products. Furthermore, it also reflects the R&D capability and innovation ability of Bontac in the field of synthetic biology, which will surely inspire Bontac to invest more actively in R&D and innovation. Figure 3: Bontac Award in FHE Dr. Qi Zhang, Founder and Chief Scientist of Bontac, delivered a speech entitled Efficient Green Biosynthesis of Ginsenosides, NMN and other Natural Products at the Innovative Technology and Innovative Manufacturing forum, explaining the green safety, wide applicability and innovative value of synthetic biotechnology from the theoretical source. Figure 4: Dr. Zhang in FHE Dr. Zhang demonstrated that Bontac holds up on the technology of biosynthesis of coenzyme preparation for natural products such as ginsenosides, especially rare ginsenosides Rh2 and Rg3. The advantages focuses on breaking through the limitations of raw materials, facilitating industrial scale-up, shorting reaction cycle, milder conditions, green environment and energy saving, but maintains the point of sustainable development. On the 23rd, a roundtable discussion on the "Technology and Investment in the Food Industry". Shu Shangke, Chairman of Bontac, attended the forum on the theme of Technology and Investment in the Food Industry and said that synthetic biotechnology is bringing about a revolution in the food and pharmaceutical fields, pushing these fields to iterate and upgrade. In the food industry, having strong R&D strength, leading technology and abundant patents are important factors for a company to have core competitiveness and investment value. Figure 5: Shu in FHE