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 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.
According to recent industrial report, only several products from worldwide NMN manufacturers came close to meeting label claim and contain not enough NMN. Almost products performed better, having at least 88% of the label claim up to small overages. A lone 250 mg product was identified as BRL. In sum, ChromaDex said that 64% of the products tested contained less than 1% of the stated amount of the active ingredient. which should give consumers pause. While this is a limited snapshot of the vast NMN finished product landscape. it does provide a glimpse into the high variability of product quality that is available. The majority of the products may purchase online contain such a small amount of NMN that there would be no clinical benefits achieved from the dose. Another concern with these adulterated products is that the actual contents are not known and could pose a risk to the user the company said in a statement.
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.
1.Raw material production process
Bioenzyme catalysis is a popular production method in the industry. It has a high threshold and several key catalytic enzymes are expensive, accounting for about 80% of the overall production process cost, but it is also the safest and most efficient production method. In the production of NMN by bioenzyme catalysis, the use of food-grade raw materials is an important part of the process to ensure product safety and to ensure that standards are followed.
2.High standard of production conditions
Production conditions refer to the standard of labor consumption required to complete the qualified products of the unit under certain production organization and production technology conditions. There are certifications issued by regulatory authorities, such as cGMP in the United States, TGA in Australia, GMP in Japan, etc.
3.High standard of product testing.
Product testing requires reliable test methods and reagents that are used throughout the production process. They are not only inspection standards for the final product, but also for the intermediate stages of control, including testing of active ingredients, testing of heavy metals such as lead, arsenic and mercury, and testing of pathogenic bacteria, microorganisms and processing by-products.
For NMN products, the commonly used method for active ingredient content testing is high performance liquid chromatography (HPLC), which is efficient, accurate and precise. For different manufacturers, the standards for testing reagents are different. Strict manufacturers will purchase high purity, analytically pure reagents from third party standards companies as controls.
4.Safety assessment
For relatively new raw materials such as NMN, it is not enough for consumers to judge the safety of the product on the side of the merchant alone. At this point, the third-party authoritative assessment report is particularly important.
Currently, there are two generic safety assessment reports, one is a toxicological assessment report and the other is a safety assessment report. In China, toxicological assessment reports usually account for the majority. However, there are still few NMN companies that can issue such reports
5.Storage and Packaging
NMNs are usually stored in sealed containers for up to 12 months. If it can be stored for 24 months with insignificant changes in purity, the stability of NMN is very reliable. Currently, the more common packaging materials are pet or hope, which are pharmaceutical packaging materials. They are non-toxic, odorless, lightweight, portable and effectively isolate air and moisture.
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 backed up 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 sold as functional food product rather 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 consumers. NMN should not be considered as 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 have been studied to discover the efficacy for 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. 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.
Introduction Wound healing is a sophisticated process responding to tissue damage, which is associated with numbers of interaction of various cell types, cytokines, growth factors, and other molecules. Strikingly, increasing the nicotinamide adenine dinucleotide (NAD) pool by nicotinamide riboside (NR) can accelerate wound healing and macrophage migration, which is partially achieved through PGE2 synthesis and signaling as well as the function of the NAD+-dependent sirtuin, SIRT3. Regulatory effects of NR on the expression of M1 macrophage markers in human MDMs. NR could modulate the expression levels of canonical M1 (inflammatory phenotype) and M2 (reparative phenotype) cell surface markers during macrophage polarization. With a great detail, a significant downregulation in CD64 and a obvious upregulation of CD197/CCR7 are viewed in the polarized M1 cells incubated with NR. Furthermore, NR increases CD197/CCR7-mediated M1 macrophage migration. The significance of chemotaxis mediator PGE2 in NR-regulated macrophage migration NR-mediated upregulation of macrophage migration through CCL19/CCR7 is dependent on the synthesis of PGE2, an inflammatory lipid mediator in the eicosanoid family. Concretely, NR administration increases the PGE2 level in cultured human monocytes, MDMs, and human serum. In addition, NR-mediated increases in CCR7 expression and CCL19-induced migration are attenuated by PGE2 synthesis blockers. NR/SIRT3/migration axis in human M1 MDMs NR facilitates collective cell migration at a SIRT3-dependent manner in human M1 MDMs during wound healing. Simply put, the degree of wound healing is compared on Day 0 and Day 2 in vehicle- or NR-treated human M1 MDMs. It is found that NR increases the relative degree of migration (relative wound healing) and the rate of wound confluence in the presence of CCL19. Besides, the relative degree of wound density (migration) is blunted by SIRT3 knockdown, while being enhanced by SIRT3 overexpression. Application prospect of NR in wound healing Chronic diabetes is often accompanied with poor wound healing. For instance, diabetic foot ulcers, one of the chief cause of amputations, affect 15% of people with diabetes. Given that NR can drive the macrophage migration to boost chronic wound healing, it may have a broad application prospect in treating the wounds including but not limited to diabetic patients. Conclusion In human macrophages, NR induces surface expression of the chemotaxis CD197/CCR7 receptor and levels of its lipid mediator PGE2 via upregulation of cyclooxygenase 2 and functionally increases macrophage migration and wound healing in a SIRT3-dependent manner. Reference Wu J, Bley M, Steans RS, et al. Nicotinamide Riboside Augments Human Macrophage Migration via SIRT3-Mediated Prostaglandin E2 Signaling. Cells. 2024;13(5):455. Published 2024 Mar 5. doi:10.3390/cells13050455 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.
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.
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.