Advantages of NMNH
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
Advantages of NADH
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
Advantages of NAD
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
Advantages of MNM
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
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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.
NAD powder manufacturing method
The preparation methods utilized by manufacturers worldwide of NAD powder are mainly divided into chemical synthesis method and biocatalytic method, among which biocatalytic method includes biological fermentation method and enzyme catalysis method. Enzyme catalysis method has gradually become the mainstream direction because of its advantages of green, environmental protection and pollution-free. And then the purity of NAD powder will reach 99% after the procedure of further purifying. But some NAD manufacturers tend to choose the multiple methods to develop the producing of NAD.
BONTAC NAD product features and advantages
1、As an advanced technology NAD manufacturer, BONTAC choose the Enzymatic method, environmental-friendly, no harmful solvent residues manufacturing powder
2、High purity（up to 99%) and stability of production of NAD powder
3、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NAD powder
4、Multiple in vivo studies show that Bontac NAD powder is safe and effective
5、Provide one-stop product solution customization service
NAD powder efficacy in health
Molecules that can be taken in supplement form to increase NAD levels in the body are referred to by some as “NAD boosters.” Studies conducted over the past six decades suggest that the following are some of the many benefits associated with taking an NAD supplement:
Can Help Restore Mitochondrial Function
Helps Repair Blood Vessels —A 2018 mice study found that supplementation could aid in repair and growth of aged blood vessels. There’s also some evidence it can help manage heart disease risk factors like high blood pressure and high cholesterol.
May Improve Muscle Function — One animal study conducted in 2016 found that degenerative muscles had improved muscle function when supplemented with NAD+ precursors.
Potentially Helps Repair Cells and Damaged DNA — Some studies have found evidence that NAD+ precursor supplementation leads to an increase in DNA damage repair. NAD+ is broken down into two component parts, nicotinamide and ADP-ribose, which combine with proteins to repair cells.
May Help Improve Cognitive Function — Several studies conducted on mice have found that mice treated with NAD+ precursors experienced improvements in cognitive function, learning and memory. Findings have led researchers to believe that NAD supplement may help protect against cognitive decline/Alzheimer’s disease.
May Help Prevent Age-Related Weight Gain — A 2012 study showed that when mice fed a high-fat diet were given an NAD supplement, they gained 60 percent less weight than they did on the same diets without the supplement. One reason this may be true is that nicotinamide adenine dinucleotide helps regulate production of stress- and appetite-related hormones, thanks to its effects on circadian rhythms.
Precursors are molecules used in chemical reactions inside the body to create other compounds. There are a number of precursors of NAD+ that result in higher levels when you consume enough of them.
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1.Prevention and treatment of viral-induced inflammatory storms
Scientists have found after extensive research that neo-coronavirus has a mechanism similar to SARS virus to activate inflammatory vesicles NLRP3. and the activation of NLRP3 produces more inflammatory factors, generating excessive inflammation and thus triggering a deadly cytokine storm. This problem can be well addressed by NAD+, which inhibits the activity of NF-κB inflammatory pathway and NLRP3 inflammasome by increasing the activity of sirtuins (SIRT1, SIRT2 and SIRT3), thus preventing cytokine storm caused by excessive inflammation. Therefore, Sinclair and other scientists believe that increasing the concentration of NAD+ may play an important role in the prevention and treatment of neocoronavirus and other viral infections.
2.Restoration of virus-induced metabolic disorders
NAD+ is an essential coenzyme for many cellular energy metabolic pathways, present in every cell of the body, involved in thousands of reactions, and an important player in maintaining cellular viability. In the COVID-19 infection model, NAD+ and NMN supplementation was found to be effective in alleviating cell death and protecting the lung.
First, inspect the factory. After some screening, NAD manufactures 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 NAD powder of high quality with the caterias of SGS. Secondly, the purity is tested. Purity is one of the most important parameters of NAD powder. If high purity NAD cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NAD 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.
In the international market, NAD+ food supplements are in production in the United States, the Australian Food and Drug Administration has approved NAD+ products for sale, and Japanese NAD+ manufactures are devoted to extend the market share in China. Li Ka-shing invested HK$200 million in the US NAD manufacturer, whose NAD+ products are being sold by Watsons in Hong Kong! Then Mclane, a company owned by Warren Buffett also joined the NAD market.
Our updates and blog posts
Targeting NAD+ Salvage Pathway as a Potential Approach to Combat Obesity
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.
NR as a Promising Therapeutic Candidate for Alpers' Disease
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.
Anti-inflammatory Function of NMN in Macrophages via IDO1/Kynurenine/AhR Axis
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.