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 99.9%) 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.
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.
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.
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.
Introduction Alpers' disease is both a neurodegenerative disorder and a metabolic disorder, which is tightly linked to mitochondrial dysfunction and mutations in the catalytic subunit of polymerase gamma (POLG) gene. Noteworthily, supplementation of NAD precursor, nicotinamide riboside (NR), is evidenced to explicitly ameliorate mitochondrial defects in cortical organoids of patients with Alpers' disease. About Alpers’ disease Alpers’ disease is an autosomal recessive disorder, which is often accompanied with cortical neuronal loss as well as depletion of mitochondrial DNA (mtDNA) and complex I (CI). The disease occurs in about 1 in 100,000 newborns. Most individuals with Alpers’ disease show no symptoms at birth. Diagnosis is generally established by determining the POLG gene. Once onset (usually between first and third years of life), patients may present the symptoms such as progressive encephalopathy, epilepsy, myoclonus, and myasthenia gravis. Currently, there is no effective method to cure this disease. Establishment of Alpers' disease model in vitro Induced pluripotent stem cells (iPSCs) are generated from Alpers' patient carrying the compound heterozygous mutations of A467T (c.1399G>A) and P589L (c.1766C>T), followed by differentiation into cortical organoids and neural stem cells (NSCs). Alpers's iPSCs exhibit mild mitochondrial alterations, including an elevated L-lactate level and a depletion of CI. Alpers' NSCs manifest profound mtDNA depletion and mitochondrial dysfunction. Alpers' cortical organoids demonstrate cortical neuronal loss and astrocyte accumulation. The role of NR in Alpers' cortical organoids Long-term treatment with NR partially ameliorates the neurodegenerative alterations observed in Alpers' cortical organoids. Specifically, supplementation of NR effectively counteracts neuronal loss, glial enrichment, and mitochondrial damage observed in cortical organoids of patients with Alpers' disease. Reversal of the dysregulated pathways in Alpers' patient organoids post NR treatment NR treatment offsets the downregulation of mitochondrial and synaptogenesis-related pathways, as well as upregulation of pathways associated with astrocyte/glial cells and neuroinflammation are obviously activated in Alpers' cortical organoids. Conclusion Replenishment of NR to increase NAD level can rescue mitochondrial defects and neuronal loss in iPSC-derived cortical organoid of Alpers’ disease, with relatively high safety and bioavailability, showing great promise as a therapeutic candidate for this intractable disorder. Reference Hong Y, Zhang Z, Yangzom T, et al. The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease. Int J Biol Sci. 2024;20(4):1194-1217. Published 2024 Jan 25. doi:10.7150/ijbs.91624 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 opinions 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 Acute lung injury comprises a uniform response of the lung to inflammatory or chemical insults which is commonly caused by systemic illness including sepsis or trauma, infection with pathogens, and toxic gas inhalation. Sepsis-induced acute lung injury is a leading cause of morbidity and mortality worldwide, imposing substantial economic, social, and health burdens. Despite advances in knowledge of septic pulmonary pathologies over the years, efficient targeted therapies are still lacking. Notably, NMN administration has been uncovered to be effective in alleviating sepsis-induced acute lung injury, which can reduce cellular inflammation, oxidative stress, and apoptosis. 2. The impact of NMN upon macrophage polarization in LPS-induced MH-S cells In mouse alveolar macrophage cell line MH-S treated by lipopolysaccharide (LPS), NMN can facilitate the transformation of macrophages from pro-inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype to promote inflammatory resolution and tissue repair, as evidenced by the downregulation of M1 phenotype-associated markers (iNOS and CD86+ F4/80+) and pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) as well as the upregulation of M2 phenotype-related markers (Arg1 and CD86+ F4/80+) and anti-inflammatory mediators (IL-10) post NMN administration. 3. The alleviation of LPS-induced lung injury post NMN administration In vitro, NMN represses the apoptosis and production of pro-inflammatory factors in LPS-stimulated MH-S cells. In vivo, NMN explicitly ameliorates LPS-induced pathological alterations, encompassing thickened alveolar wall, inflammatory cell infiltration, septa swelling, and erythrocyte exudation, in a murine septic model. 4. The association of SIRT1/NF-κB signaling activation with NMN-mediated macrophage polarization SIRT1/NF-κB signaling pathway is involved in the lung protection of NMN, as manifested by the elevated expression of SIRT1 as well as the reduced acetylation and phosphorylation of NF-κB-p65 post NMN treatment. Repression of SIRT1/NF-κB signaling offsets NMN-mediated M2 macrophage polarization. SIRT1 inhibitor EX-527 decreases the expression of SIRT1, yet increases the expression of acetylated and phosphorylated NF-κB-p65 in septic mice pretreated with NMN. In contrast to NMN, EX-527 overtly promotes the expression levels of M1 macrophage-associated markers (iNOS and CD86) while inhibiting those of M2 phenotype-related markers (Arg1 and CD206). 5. Conclusion NMN can effectively ameliorate LPS-induced acute lung injury through modulating macrophage polarization via SIRT1/NF-κB signalling pathway, providing a novel therapeutic direction for sepsis-induced acute lung injury. 6. Reference He, Simeng et al. “Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway.” Pharmaceutical biology vol. 62,1 (2024): 22-32. doi:10.1080/13880209.2023.2292256 BONTAC NMN BONTAC is the leader of the global NMN industry, with 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 160 invention patents including 15 NMN patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. Both the high-quality product and excellent service can be better ensured in BONTA. BONTAC has 12 years of industry experience, which is worthy of your trust. 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.
1. Introduction Supplementation of nicotinamide mononucleotide (NMN) to upregulate the level of nicotinamide adenine dinucleotide (NAD+) has been unveiled to be a promising anti-aging intervention. However, it is still a serious challenge to accurately quantify NAD+ intermediates, NMN in particular. This study is powered to introduce a novel method, double isotope-mediated LC-MS/MS methodology (dimeLC-MS/MS), for the precise quantification of NMN in biological samples. 2. Factors affecting the accurate detection of NMN NMN is hard to be accurately detected due to its vulnerability to enzymatic degradation, conversion in sample processing, its complex behaviors in different column and extraction conditions, as well as matrix effect. Specifically, NMN has the properties of high polarity and low volatility, which is easy to dissolve in water but difficult to dissolve in organic solvents. These properties greatly restrict the application of many conventional quantitative analysis methods. Biological samples such as blood carries significant activities of CD38 and CD73 (ecto-5’-nucleotidase), both of which could use NMN as a substrate. The behavior of NMN in the column is very complex probably because of the bipartite nature of its charges so that subtle differences in extraction and column conditions significantly affect the reliable and accurate detection of NMN. 3. Coping strategies of dimeLC-MS/MS to reduce the impact of impact factors To avoid the interference of above-mentioned factors, a prototype column NMN-2 is applied. This column contains C18-based high-purity silica particles which are more capable of binding hydrophilic compounds than carbon particles, improving the ability of separation. Perchloric acid (PCA) is employed since it can efficiently extract NAD+ and NMN from biological samples such as plasma with minimal losses. To adjust for matrix effects, a fixed amount (1 μM) of each isotopic compound is added to biological samples prior to the PCA extraction. 4. The advantages of dimeLC-MS/MS Double isotopic NMN standards, NMN (M + 14) and NMN (M + 5), in the LC-MS/MS-driven methodology can precisely trace the fate of NMN during sample processing, which significantly increases the accuracy and the reliability of NMN measurement in biological samples. Besides, dimeLC-MS/MS can evaluate the extraction efficiency and the absolute concentrations of NMN in different types of biological samples. 5. Conclusion This new LC-MS/MS-driven methodology with double isotopic NMN standards can accurately and reliably measure NMN in biological samples. It can be used for future studies on NMN intake. 6. Reference Unno, Junya et al. “Absolute quantification of nicotinamide mononucleotide in biological samples by double isotope-mediated liquid chromatography-tandem mass spectrometry (dimeLC-MS/MS).” npj aging vol. 10,1 2. 2 Jan. 2024, doi:10.1038/s41514-023-00133-1 Why choose BONTAC? BONTAC is the leader of the global NMN industry. We have the first whole-enzyme catalysis technology in China, and have become the leading enterprise in coenzyme products which are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. Notably, BONTAC is NMN raw material supplier of famous David Sinclair team at the Harvard University. Our services and products are trustworthy. Furthermore, BONTAC has an independent coenzyme engineering technology research center at the provincial level in China and self-owned factories, where the purity ans stability of products can be ensured. 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.