NMNH: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder. 2. Bontac is a very first manufacture in the world to produce the NMNH powder on the level of high purity, stability. 3. Exclusive “Bonpure” seven-step purification technology, high purity（up to 99%) and stability of production of NMNH powder 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMNH powder 5. Provide one-stop product solution customization service
NADH: 1. Bonzyme whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive Bonpure seven-step purification technology, purity up higher than 98 % 3. Special patented process crystal form, higher stability 4. Obtained a number of international certifications to ensure high quality 5. 8 domestic and foreign NADH patents, leading the industry 6. Provide one-stop product solution customization service
NAD: 1. “Bonzyme” Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Stable supplier of 1000+ enterprises around the world 3. Unique “Bonpure” seven-step purification technology, higher product content and higher conversion rate 4. Freeze drying technology to ensure stable product quality 5. Unique crystal technology, higher product solubility 6. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products
NMN: 1. “Bonzyme”Whole-enzymatic method, environmental-friendly, no harmful solvent residues 2. Exclusive“Bonpure”seven-step purification technology, high purity（up to 99.9%) and stability 3. Industrial leading technology: 15 domestic and international NMN patents 4. Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products 5. Multiple in vivo studies show that Bontac NMN is safe and effective 6. Provide one-stop product solution customization service 7. NMN raw material supplier of famous David Sinclair team of Harvard University
Bontac Bio-Engineering (Shenzhen) Co., Ltd. (hereafter referred to as BONTAC) is a high-tech enterprise established in July 2012. BONTAC integrates R&D, production and sales, with enzyme catalysis technology as the core and coenzyme and natural products as main products. There are six major series of products in BONTAC, involving coenzymes, natural products, sugar substitutes, cosmetics, dietary supplements and medical intermediates.
As the leader of the global NMN industry, BONTAC has the first whole-enzyme catalysis technology in China. Our coenzyme products are widely used in health industry, medical & beauty, green agriculture, biomedicine and other fields. BONTAC adheres to independent innovation, with more than 170 invention patents. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. What’s more, BONTAC has established the first coenzyme engineering technology research center at the provincial level in China which also is the sole in Guangdong Province.
In the future, BONTAC will focus on its advantages of green, low-carbon and high-value-added biosynthesis technology, and build ecological relationship with academia as well as upstream/downstream partners, continuously leading the synthetic biological industry and creating a better life for human beings.
BONTAC is a reliable partner that we have been working with for many years. The purity of their coenzyme is very high. Their COA can achieve relatively high test results.
I discovered BONTAC in 2014 because David's article in cell about NAD and NMN related showed that he used BONTAC's NMN for his experimental material. Then we found them in China. After so many years of cooperation, I think it is a very good company.
I think green, healthy and high purity are the advantages of BONTAC's products compared with others. I still work with them to this day.
In 2017, we chose BONTAC's coenzyme, during which our team encountered many technical problems and consulted their technical team, which were able to give us good solutions. Their products are shipped very fast and they work more efficiently.
<p>NMN supplements may cause side effects such as upset stomach, diarrhea, and nausea. There is also research showing that NMN supplements may affect insulin sensitivity and insulin levels, so people with diabetes should consult their doctor before taking them.</p>
<p>NMN supplements have not yet undergone large-scale clinical trials to verify their effectiveness. Currently, research on NMN supplements is mainly focused on animal and in vitro experiments. These studies show that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity, and can delay the aging process.</p>
<p>The long-term health effects of NMN supplementation are not well studied. Existing studies mainly focus on animal and in vitro experiments, which show that NMN can improve the symptoms of metabolic diseases such as diabetes, fatty liver and obesity, and can delay the aging process. However, the results of these studies do not represent the long-term effects of NMN on human health.</p>
1. Introduction Nicotinamide adenine dinucleotide (NAD) has been unveiled to be essential for embryonic development. Patients with genetic variants in the NAD+ de novo synthesis pathway often have congenital NAD deficiency disorder (CNDD), a multisystem condition inherited in an autosomal recessive manner. In the context of NAD+ deficiency, all organs and systems, not just vertebrae, heart, kidneys, and limbs, may be affected. 2. The association between NAD synthetase 1 (NADSYN1) and CNDD Individuals delivering biallelic NADSYN1 variants share similar clinical features to those with CNDD. Up till now, almost all of the identified CNDD cases can be attributed to biallelic loss-of-function variants in any of 3 nonredundant genes of the NAD de novo synthesis pathway, including kynureninase (KYNU), 3-hydroxyanthranilate 3,4-dioxygenase (HAAO), or NADSYN1. Among individuals with CNDD identified to date, those with biallelic pathogenic NADSYN1 variants are the most diverse in phenotype. 3. The impact of NADSYN1 variants upon enzymatic activity and phenotype Specifically, NADSYN1 can catalyse the amidation of nicotinic acid adenine dinucleotide (NaAD) to NAD. Biallelic pathogenic variants in NADSYN1 cause a metabolic block in both the de novo pathway and the Preiss-Handler pathway, leading to NAD deficiency. Biallelic NADSYN1 loss-of-function variants impact the NAD metabolome of humans. Post-birth phenotypes involve feeding difficulties, developmental delay, short stature, etc. 4. Mouse embryogenesis disrupted by the loss of NADSYN1 In NADSYN1-/- mouse embryos, NAD-dependent malformations occur when maternal dietary NAD precursors are limited during gestation. The affected Nadsyn1-/- embryos most frequently present malformations of the kidneys, eyes, and lungs. 5. The preventative effect of amidated NAD precursor supplementation against CNDD NADSYN1-dependent embryo loss and malformation in mice are preventable by dietary supplementation of amidated NAD precursors (NMN and NAM) during pregnancy. Maternal diet–derived NAD precursors primarily determine the development of healthy embryos. 6. Conclusion NAD-boosting supplements are essential for individuals with biallelic loss-of-function variants in NADSYN1. Maternal NAD precursor supplementation, to some extent, can reduce the risk of developing CNDD. Reference Szot JO, Cuny H, Martin EM, et al. A metabolic signature for NADSYN1-dependent congenital NAD deficiency disorder. J Clin Invest. 2024;134(4):e174824. Published 2024 Feb 15. doi:10.1172/JCI174824 About BONTAC BONTAC has been dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 170 global patents as well as strong R&D team consisting of Doctors and Masters. BONTAC has rich R&D experience and advanced technology in the biosynthesis of NAD and its precursors (eg. NMN and NR), with various forms to be selected (eg. endoxin-free IVD-grade NAD, Na-free or Na-containing NAD; NR-CL or NR-Malate). High quality and stable supply of products can be better ensured here with the exclusive Bonpure seven-step purification technology and Bonzyme Whole-enzymatic method. Disclaimer This article is based on the reference in the academic journal. The relevant information is provide for sharing and learning purposes only, and does not represent any medical advice purposes. If there is any infringement, please contact the author for deletion. The views expressed in this article do not represent the position of BONTAC. 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 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.
Introduction The crucial parts of nicotinamide adenine dinucleotide (NAD+) and its metabolites in aging and neurodegeneration have been widely recognized. To spur progress toward biochemical research and interventions targeting aging and neurodegenerative diseases, it is of great significance to accurately quantify NAD+ and its metabolite levels in the NAD+ salvage pathway. Here, a robust and accurate LC-MS/MS method is applied to quantify NAD+ and its metabolites levels in normal and injured mouse sciatic nerve. Limitations of existing methods for quantifying NAD+ and its metabolites Traditional methods for quantifying NAD+ and its metabolites, such as HPLC-UV, NMR, capillary zone electrophoresis, or colorimetric enzymatic assays, face various challenges in sensitivity, selectivity, and indirect measurement. As for existing LC-MS/MS assays for cellular or tissue NAD+ and its metabolites measurements, there are still many difficulties to overcome, such as extended run times, poor chromatographic retention behavior, and unsatisfactory peak shapes. Moreover, only one to three substances in the NAD+ salvage pathway can be covered by these methods. The modifications of LC-MS/MS method On the basis of existing LC-MS/MS assays, the modifications regarding the chromatographic conditions, surrogate matrix and MS/MS conditions are conducted. Specifically, 5 μM of methylene phosphonic acid is employed as the mobile phase additive, which explicitly promotes the signal intensity and peak shape. Given the relatively clean and simple nature of never samples and their small size, ultrapure water is tested as a substitute matrix. Instead of hydrophilic interaction liquid chromatography column and hypercarb column, the Waters Atlantis Premier BEH C18 AX column is utilized, whose unique MaxPeak HPS high-performance surface technology (passivating the column inner wall, eliminating metal surface) enables the high reproducibility, peak symmetry, and baseline separation of all analytes. Besides, MS conditions are optimized to minimize the NAD+ interference signal in the cyclic adenosine diphosphate ribose (cADPR) channel while maintaining the response of cADPR and nicotinamide mononucleotide (NMN), with 4000V for ion spray voltage, 450℃ for turbo heater temperature, 50 psi for Gas 1, 50 psi for Gas 2, 30 psi for curtain gas, and 12 psi for collision gas. Representative chromatogram of nerve samples (normal vs injured) All five analytes achieve baseline separation, where cADPR is a sensitive biomarker in the neurodegeneration model. Herein, sciatic nerve axotomy induces axonal degeneration, leading to reduced NAD+ level and elevated NMN level in the injured nerves, resulting in about a 2-fold increase in the NMN/NAD+ ratio. Simultaneously, the levels of nicotinamide (NAM) and adenosine diphosphate ribose (ADPR), are decreased by about 2-fold, while cADPR level is increased by more than 8-fold. These results are consistent with those of previously reported research, verifying the accuracy of this modified LS-MS/MS method in quantifying NAD+ and its metabolites. Conclusion This modified LC-MS/MS method enables effective baseline separation of NAD+, NMN, NAM, ADPR, and cADPR within a brief runtime of 5 min, which is contributive to early diagnoses of various neurological disorders and drug development for aging and neurodegenerative diseases. Reference Ma Y, Deng L, Du Z. Development and validation of an LC-MS/MS method for quantifying NAD+ and related metabolites in mice sciatic nerves and its application to a nerve injury animal model. J Chromatogr A. doi:10.1016/j.chroma.2024.464821 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. Under no circumstances will BONTAC be held responsible or liable in any way 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.