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 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.
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.
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 Ginsenoside Rg3 is Panaxanediol type tetracyclic triterpenoid saponin monomer extracted from the root of Panax ginseng, which has a wide range of pharmacological effects including anti-tumor, neuroprotection, cardiovascular protection, anti-fatigue, anti-oxidation, hypoglycemia, and enhancement of immune function. This research unveils the potential value of ginsenoside Rg3 in targeting breast cancer stem cells (BCSCs) to treat breast cancer, one of the most common tumor worldwide with significant morbidity and mortality. Ginsenoside Rg3 as anticancer adjuvant Ginsenoside Rg3 can promote the apoptosis of tumor cells, and inhibit tumor growth, infiltration, invasion, metastasis and neovascularization. At the same time, it has the effect of reducing toxicity, increasing efficacy in the joint application with chemotherapeutic drugs, improving immunity of the organism, and reversing multi-drug resistance of tumor cells. Shenyi capsule, a new anticancer drug with ginsenoside Rg3 monomer as the main component, was approved by China FDA and marketed in 2003, which is mainly used in the adjuvant treatment of various tumors. About BCSCs Breast cancer stem cells (BCSCs) are a group of undifferentiated cells with strong ability of self-renewal and differentiation, which is the main reason for poor clinical outcomes and poor efficacy. BCSCs can clonally proliferate under serum-free three-dimensional culture conditions and form mammospheres. BCSCs have specific surface markers (CD44, CD24, CD133, OCT4 and SOX2) or enzymes (ALDH1). BCSCs function as potential drivers of breast cancer, which are resistant to conventional breast cancer clinical treatments such as radiotherapy, leading to breast cancer recurrence and metastasis. The suppressive effect of ginsenoside Rg3 in the progression of breast cancer Ginsenoside Rg3 exerts inhibitory effects on the viability and clonogenicity of breast cancer cells in a time- and dose-dependent manner. In addition, it suppresses mammosphere formation, as evidenced by the spheroid number and diameter. Furthermore, ginsenoside Rg3 reduces the expression of stem cell-related factors (c-Myc, Oct4, Sox2, and Lin28), and decreases the ALDH (+) subpopulation breast cancer cells. Ginsenoside Rg3 as an accelerator of MYC mRNA degradation Ginsenoside Rg3 depresses BCSCs mainly through downregulating the expression of MYC, one of the main cancer stem cell reprogramming factors with a pivotal role in tumor initiation. Its regulatory effect on MYC mRNA stability is chiefly achieved by promoting the microRNA let-7 cluster. Under normal conditions, the let7 family is expressed at low levels in cancer cells, resulting in stable MYC mRNA expression and high c-Myc expression. However, Rg3 treatment leads to the upregulation of let-7 cluster, impairment of MYC mRNA stability, downregulation of c-Myc expression and inhibition of breast cancer stem-like properties. Conclusion The traditional Chinese herbal monomer ginsenoside Rg3 has the potential to suppress breast cancer stem-like properties by destabilizing MYC mRNA at the post-transcriptional level, showing great promise as adjuvant for the treatment of breast cancer. Reference Ning JY, Zhang ZH, Zhang J, Liu YM, Li GC, Wang AM, Li Y, Shan X, Wang JH, Zhang X, Zhao Y. Ginsenoside Rg3 decreases breast cancer stem-like phenotypes through impairing MYC mRNA stability. Am J Cancer Res. 2024 Feb 15;14(2):601-615. PMID: 38455405; PMCID: PMC10915333. 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 for any claims, damages, losses, expenses, or costs whatsoever 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 Replenishing nicotinamide mononucleotide (NMN) to raise the availability of nicotinamide adenine dinucleotide (NAD+) has been deemed as effective approach to prevent neurodegeneration in aging and pathological conditions including ALS, a fatal progressive neurodegenerative disorder with no known way to cure. The association of SOD1 and TDP-43 with ALS Cu/Zn-superoxide dismutase (SOD1) is the first identified protein associated with familial ALS. In most ALS cases, Transactive Response DNA Binding Protein 43 (TDP-43) pathology is frequently observed. Both SOD1 and TDP-43 have tight association with motor neuron degeneration in patients with ALS. Mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions. Mutant SOD1G93A and the fragment form of TDP-43 can exert synergistic effect to mediate toxic events in apoptosis. The protective effect of NMN on motor neurons NMN can increase the neurite length and complexity in mouse motor neurons and iPSC-derived human motor neurons overexpressing wild-type TDP-43/mutant hSOD1G93A. Meanwhile, it prevents the neuronal death and increased nitro-tyrosine immunoreactivity induced by trophic factor deprivation. In motor neurons overexpressing mutant hSOD1G93A, the neuroprotection conferred by NMN supplementation is mediated by a mechanism that involves an increase in glutathione content. However, this neuroprotective effect does not involve the alteration of glutathione content in non-transgenic or TDP-43 overexpressing motor neurons. The involvement of TDP-43 pathology in ALS NMN supplementation can confer axonal protection in motor neurons isolated from two dissimilar models of ALS, with and without involvement of TDP-43 pathology. Besides, NMN treatment correct the morphological changes induced by TDP-43 overexpression in motor neurons and boost the nuclear localization of TDP-43 and phosphorylated TDP-43, which favors its nuclear localization and averts the detrimental effects of TDP-43 overexpression on neurite length and complexity. Conclusion Supplementation of NAD+ precursor NMN can modulate neurite complexity and survival in motor neurons, showing great therapeutic potential in the context of ALS pathology. Reference [1] Hamilton HL, Akther M, Anis S, Colwell CB, Vargas MR, Pehar M. NAD+ precursor supplementation modulates neurite complexity and survival in motor neurons from ALS models. Antioxid Redox Signal. Published online March 19, 2024. doi:10.1089/ars.2023.0360 [2] Jeon GS, Shim YM, Lee DY, et al. Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations. Mol Neurobiol. 2019;56(3):2007-2021. doi:10.1007/s12035-018-1218-2 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 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. .