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.
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.
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.
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 Rare ginsenoside Rg3, an active extract from Panax ginseng, is reported to possess a wide range of pharmacological properties including anti-angiogenesis and anti-cancer, with high lipophilicity (estimated log P4) and a low water solubility at pH7.4. Nevertheless, its permeability and bioavailability are relatively low, and production procedures are complex. Remarkably, the metabolites of Rg3 have similar and even stronger activity than Rg3, opening up new opportunities for future adjuvant cancer therapy. The association of ginsenoside Rg3 and its metabolites There are two epimers of ginsenoside Rg3, which can be subsequently deglycosylated into epimers of ginsenoside Rh2 (S-Rh2 and R-Rh2) and protopanaxadiol (S-PPD and R-PPD). The anti-cancer properties of Rg3 metabolites Angiogenesis and tumor cell proliferation are both interdependent factors in tumor progression. In terms of anti-proliferation, Rg3 metabolites, who induce S-phase arrest and necroptosis in a human triple negative breast cancer cell line MDA-MB-231 as well as G0/G1 arrest and apoptosis in human umbilical vein endothelial cells (HUVECs), are more potent than Rg3. The clinically relevant target of Rg3 metabolites are the endothelial cells. Anti-angiogenic effects are evaluated using loop formation assay. Among Rg3 metabolites, S-Rh2 is the most potent inhibitor of loop formation. VEGFR2 and AQP1 as the targets of Rh2 According to the prediction by in silico molecular docking, there is a good binding score between Rh2/PPD and the ATP-binding pocket of VEGFR2, a dominant regulator controlling both physiological and pathological angiogenesis. Through VEGF bioassay, it is discovered that S-Rh2 is a most potent anti-angiogenic candidate with allosteric modulatory action on VEGFR2 function. In addition, Rh2 and PPD have the potential of blocking AQP1 and AQP5, two members of the aquaporin family with vital roles in proliferation, migration, invasion and angiogenesis. Moreover, Rg3 is more selective for AQP1 and does not show a good binding score with AQP5. In light of this, blocking the water channel function of AQP1 may have an immediate role in inhibition of loop formation and anti-angiogenic effects of Rh2. Conclusion Metabolites of Rg3 could potentially increase the anti-cancer properties of Rg3. The application of these molecules alone or together may be potent alternatives for future adjuvant cancer therapy. Reference Nakhjavani M, Smith E, Yeo K, et al. Differential antiangiogenic and anticancer activities of the active metabolites of ginsenoside Rg3. J Ginseng Res. 2024;48(2):171-180. doi:10.1016/j.jgr.2021.05.008 BONTAC Ginsenosides 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 rare ginsenosides Rh2/Rg3, with pure raw materials, higher conversion rate and higher content (up to 99%). One-stop service for customized product solution is available in BONTAC. With unique Bonzyme enzymatic synthesis technology, both S-type and R-type isomers can be accurately synthesized here, with stronger activity and precise targeting action. 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 NADH (reduced form of NAD+) serves as a carrier of biological hydrogen and an electron donor, which participates in diverse physiological processes such as protein synthesis, DNA repair, insulin synthesis and secretion, immune response and cell division, playing a critical role in promoting health span and mitigating various disease states. Major enzymatic reactions in substrate metabolism that are dependent upon NAD+/NADH ratio The equilibrium of the NAD+/NADH ratio is vital for maintaining cellular reduction–oxidation (redox) homeostasis and modulating energy metabolism. Several enzymatic reactions in substrate metabolism are carried out in a NAD+/NADH ratio-dependent way. For instance, ketones suppress the increased mitochondrial production of ROS associated with excitotoxic injury by enhancing NADH oxidation (i.e. elevated NAD+/NADH ratio) in the electron transport chain, directly affecting NADH level . NADH in Krebs cycle and glycolysis NADH is produced in glycolysis and the Krebs cycle (also known as citric acid cycle or tricarboxylic acid cycle), which can transfer energy to supply ATP synthesis through the process of oxidative phosphorylation in the inner membrane of the mitochondria. Krebs cycle supplies NADH as an electron carrier to the electron transport chain in mitochondria, while glycolysis-produced NADH can be used by L-lactate dehydrogenase (LDH) or transported to the mitochondria for redox homeostasis. The effects of NADH on the mitochondria are accomplished by specialized shuttle systems (e.g., malate-aspartate or glycerol-3-phosphate). The possible strategies to modulate NADH level The main NAD/NADH biosynthetic pathways include de novo synthesis from tryptophan (TRP), synthesis from either form of vitamin B3, nicotinamide (NAM) or nicotinic acid (NA), or conversion of nicotinamide riboside (NR). Correspondingly, NADH level can be regulated by replenishing NADH precursors (eg. NR and NMN), applying NADH dehydrogenase inhibitors, having diets rich in certain nutrients (eg. vitamin B3), administrating mitochondrial targeting agents and supplementing exogenous NADH. Conclusion NADH may be a versatile therapeutic candidate by leverage of its ability to affect redox homeostasis, mitochondrial functions, and enzymatic reactions. Reference Schiuma G, Lara D, Clement J, Narducci M, Rizzo R. NADH: the redox sensor in aging-related disorders. Antioxid Redox Signal. Published online February 17, 2024. doi:10.1089/ars.2023.0375 BONTAC NADH 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 and over 170 global patents including 8 NADH patents. The purity of BONTAC NADH can reach over 98%. BONTAC NADH has been widely applied in anti-aging health products, diagnostic reagent raw materials, HCY Homocysteine Test Kit, Biomedical R&D, and functional food and beverage. 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.
1. Introduction Nicotinamide mononucleotide (NMN) supplementation has been suggested to hamper the inflammatory responses via restoring NAD+ level and downregulating the expression of Cyclooxygenase-2 (COX-2). Strikingly, both Aryl hydrocarbon receptor (AhR) and Indoleamine 2,3-Dioxygenase 1 (IDO1), two key enzymes for kynurenine production, can mediate the anti-inflammatory function of NMN in RAW 264.7 macrophages. 2. The alleviated inflammatory response in the presence of NMN supplementation For deciphering the impact of NMN in vivo, mice are subjected to daily intraperitoneal (i.p.) injection of NMN (500 mg/kg) for consecutive 6 days, followed by i.p. injection of lipopolysaccharides (LPS) (5 mg/kg) or alum (700 μg) on day 7. It is discovered that NMN supplementation suppresses LPS- or alum-induced inflammation in mice, as manifested by the downregulation of proinflammatory cytokines (IL-6 and IL-1β) and proinflammatory enzyme (COX-2). 3. The necessity of AhR for NMN-mediated inhibition of inflammatory response in macrophages AhR, a ligand-activated transcription factor, can mediate the anti-inflammatory function of NMN upon LPS treatment in RAW264.7 cells. Specifically, NMN reduces the expression of COX-2 in cells in bearing AHR. On the contrary. AhR inhibitor (CH223191) deprives the downregulation of IL-6, IL-1β and COX-2 caused by NMN treatment. Likewise, NMN treatment fails to reduce the expression levels of IL-6, IL-1β, and COX-2 in AhR knockout cells. 4. The importance of IDO1/kynurenine/AhR axis in the anti-inflammation function of NMN IDO1 is the rate-limiting enzyme in tryptophan catabolism to produce kynurenine, a metabolic intermediate in NAD+ de novo synthesis pathway. Kynurenine can promote the translocation of AhR from the cytoplasm to nucleus, thereby exerting an anti-inflammatory effect. NMN inhibits LPS-induced inflammation in a IDO1-kynurenine dependent manner in macrophages. 5. Conclusion NMN supplementation mitigates COX-2-associated inflammatory responses by activating lDO-kynurenine-AhR pathway, providing new insights into NAD* regulation in macrophage activation. Reference Liu J, Hou W, Zong Z, et al. Supplementation of nicotinamide mononucleotide diminishes COX-2 associated inflammatory responses in macrophages by activating kynurenine/AhR signaling. Free Radic Biol Med. Published online February 8, 2024. doi:10.1016/j.freeradbiomed.2024.01.046 BONTAC NMN BONTAC is the pioneer of NMN industry and the first manufacturer to launch NMN mass production, with the first whole-enzyme catalysis technology around the world. At present, BONTAC has become the leading enterprise in niche areas of coenzyme products. Notably, BONTAC is the NMN raw material supplier of famous David Sinclair team at the Harvard University, who uses the raw materials of BONTAC in a paper titled “Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging”. Our services and products have been highly recognized by global partners. Furthermore, BONTAC has the first national and the only provincial independent coenzyme engineering technology research center in Guangdong, China. The coenzyme products of BOMNTAC are widely used in fields such as nutritional health, biomedicine, medical beauty, daily chemicals and green agriculture. 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. 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.