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.
NADH powder manufacturing method
The main methods of NADH powder preparation include extraction, fermentation, fortification, biosynthesis and organic matter synthesis. Compared with other preparations, the whole enzyme become the mainstream method owing to the advantages of pollution free, high level of purity and stability.
BONTAC NADH product features and advantages
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%) and stability of production of NADH powder
3、Self-owned factories and obtained a number of international certifications to ensure high quality and stable supply of products of NMN powder
4、Provide one-stop product solution customization service
NADH powder efficacy in health
Improved energy levels
Not only does NADH act as an important coenzyme in aerobic respiration, the [H] of NADH also carries a large amount of energy. Studies have demonstrated that extracellular use of NADH promotes increased intracellular ATP levels, suggesting that NADH penetrates cell membranes and elevates intracellular energy levels. On a macro level, exogenous supplementation of NADH helps to restore energy and enhance appetite. The increase in energy levels in the brain also helps to improve mental performance and sleep quality. NADH has been used overseas to improve chronic fatigue syndrome, increase exercise endurance, jet lag and other areas.
Cellular protection
NADH is a strong antioxidant that naturally occurs in cells and reacts with free radicals to inhibit lipid peroxidation, protecting mitochondrial membranes and mitochondrial function. It has been found that NADH can reduce oxidative stress in cells caused by various factors such as radiation, drugs, toxic substances, strenuous exercise and ischemia, thus protecting vascular endothelial cells, hepatocytes, cardiomyocytes, fibroblasts and neurons. Therefore, injectable or oral NADH is used clinically to improve cardiovascular and cerebrovascular diseases, and as an adjunct to cancer radiotherapy. Topical NADH has been shown to be effective in the treatment of rosacea and contact dermatitis.
Promotion of neurotransmitter production
Studies have shown that NADH significantly promotes the production of the neurotransmitter dopamine, a chemical signal that is essential for short-term memory, involuntary movements, muscle tone and spontaneous physical responses. It also mediates the release of growth hormone and determines muscle movement. Without sufficient dopamine, muscles become stiff. Parkinson's disease, for example, is caused in part by a disruption of dopamine synthesis in brain cells. Preliminary clinical data suggest that NADH can help improve the symptoms of Parkinson's disease [9]. NADH also promotes the biosynthesis of norepinephrine and serotonin, showing good potential for use in the relief of depression and Alzheimer's disease.
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Frequently Asked Question
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NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.
The action of supplemental NADH is unclear. Oral NADH supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia. Researchers are also studying the value of NADH supplements for improving mental function in people with Alzheimer's disease, and minimizing physical disability and relieving depression in people with Parkinson's disease. Some healthy individuals also take NADH supplements orally to improve concentration and memory capacity, as well as to increase athletic endurance. However, to date there have been no published studies to indicate that using NADH is in any way effective or safe for these purposes
First, inspect the factory. After some screening, NADH companies 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 NADH 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 NADH powder produced by Bontac reach the purity of 99%. 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.
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The latest research proves: Coenzyme NAD+ can enhance tumor immunity! Expert Comment from Chinese Academy of Sciences
On August 10, 2021, researchers from Shanghai University of Science and Technology published an article titled NAD+ supplement potentiates tumor killing function by rescuing defective TUBBY-mediated NAMPT transcription in tumor infiltrated T cells in Cell Reports, revealing that NAD+ in supplemented during CAR-T therapy and immune checkpoint inhibitor therapy, it can improve the anti-tumor activity of T. At present, the supplementary precursor of NAD+, as a nutritional product,has been verified for human consumption safety.This achievement provides a simply and feasible new method for improving the anti-tumor activity of T cells. Cancer immunotherapies including the adoptive transfer of naturally occurring tumor-infiltrating lymphocytes (TILs) and genetically engineered T cells, as well as the use of immune checkpoint blockade (ICB) to boost the function of T cells, have emerged as promising approaches to achieve durable clinical responses of otherwise treatment-refractory cancers (Lee et al., 2015; Rosenberg and Restifo, 2015; Sharma and Allison, 2015). Although immunotherapies have been successfully used in the clinic, the number of patients benefiting from them is still limited (Fradet et al., 2019; Newick et al., 2017). Tumor microenvironment (TME)-related immunosuppression has emerged as the major reason for low and/or no response to both immunotherapies (Ninomiya et al., 2015; Schoenfeld and Hellmann, 2020). Therefore, efforts to investigate and overcome TME-related limitations in immune therapies are of great urgency. The fact that immune cells and cancer cells share many fundamental metabolic pathways implies an irreconcilable competition for nutrients in TME (Andrejeva and Rathmell, 2017; Chang et al., 2015). During uncontrolled proliferation, cancer cells hijack alternative pathways for more rapid metabolite generation (Vander Heiden et al., 2009). As a consequence, nutrient depletion, hypoxia, acidity, and generation of metabolites that can be toxic in the TME may hinder successful immunotherapy (Weinberg et al., 2010). Indeed, TILs often experience mitochondrial stress within growing tumors and become exhausted (Scharping et al., 2016). Interestingly, multiple studies also indicate that metabolic changes in TME could re-shape T cell differentiation and functional activity (Bailis et al., 2019; Chang et al., 2013; Peng et al., 2016). All these evidences inspired us to hypothesize that metabolic reprogramming in T cells might rescue them from a stressed metabolic environment, thereby reinvigorating their anti-tumor activity (Buck et al., 2016; Zhang et al., 2017). In this current study, by integrating both genetic and chemical screens, we identified that NAMPT, a key gene involved in NAD+ biosynthesis, was essential for T cell activation. NAMPT inhibition led to robust NAD+ decline in T cells, thereby disrupting glycolysis regulation and mitochondrial function, blocking ATP synthesis, and dampening the T cell receptor (TCR) downstream signaling cascade. Building on the observation that TILs have relatively lower NAD+ and NAMPT expression levels than T cells from peripheral blood mononuclear cells (PBMCs) in ovarian cancer patients, we performed genetic screening in T cells and identified that Tubby (TUB) is a transcription factor for NAMPT. Finally, we applied this basic knowledge in the (pre) clinic and showed very strong evidence that supplementation with NAD+ dramatically improves the anti-tumor killing activity both in adoptively transferred CAR-T cells therapy and immune check point blockade therapy, indicating their promising potential for targeting NAD+ metabolism to better treat cancers. 1.NAD+ regulates the activation of T cells by affecting energy metabolism After antigen stimulation, T cells undergo metabolic reprogramming, from mitochondrial oxidation to glycolysis as the main source of ATP. While maintaining sufficient mitochondrial functions to support cell proliferation and effector functions.Given that NAD+ is the main coenzyme for redox, the researchers verified the effect of NAD+ on the level of metabolism in T cells through experiments such as metabolic mass spectrometry and isotope labeling. The results of in vitro experiments show that NAD+ deficiency will significantly reduce the level of glycolysis, TCA cycle and electron transport chain metabolism in T cells. Through the experiment of replenishing ATP, the researchers found that the lack of NAD+ mainly inhibits the production of ATP in T cells, thereby reducing the level of T cell activation. 2.The NAD+ salvage synthesis pathway regulated by NAMPT is essential for T cell activation The metabolic reprogramming process regulates the activation and differentiation of immune cells. Targeting T cell metabolism provides an opportunity to modulate the immune response in a cellular way. Immune cells in the tumor microenvironment, their own metabolic level will also be correspondingly affected. The researchers in this article have discovered the important role of NAMPT in the activation of T cells through genome-wide sgRNA screening and metabolism-related small molecule inhibitor screening experiments. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme for redox reactions and can be synthesized through the salvage pathway, de novo synthesis pathway, and Preiss-Handler pathway. The NAMPT metabolic enzyme is mainly involved in the NAD+ salvage synthesis pathway. Analysis of clinical tumor samples found that in tumor-infiltrating T cells, their NAD+ levels and NAMPT levels were lower than other T cells. Researchers speculate that NAD+ levels may be one of the factors that affect the anti-tumor activity of tumor-infiltrating T cells. 3.Supplement NAD+ to enhance the anti-tumor activity of T cells Immunotherapy has been exploratory research in cancer treatment, but the main problem is the best treatment strategy and the effectiveness of immunotherapy in the overall population. Researchers want to study whether enhancing the activation ability of T cells by supplementing NAD+ levels can enhance the effect of T cell-based immunotherapy. At the same time, in the anti-CD19 CAR-T therapy model and anti-PD-1 immune checkpoint inhibitor therapy model, it was verified that supplementation of NAD+ significantly enhanced the tumor-killing effect of T cells. The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while the CAR-T treatment group without NAD+ supplemented only about 20 % Of mice achieved tumor clearance. Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors are relatively tolerant to anti-PD-1 treatment, and the inhibitory effect is not significant. However, the growth of B16F10 tumors in the anti-PD-1 and NAD+ treatment group could be significantly inhibited. Based on this, NAD+ supplementation can enhance the anti-tumor effect of T cell-based immunotherapy. 4.How to supplement NAD+ The NAD+ molecule is large and cannot be directly absorbed and utilized by the human body. The NAD+ directly ingested orally is mainly hydrolyzed by brush border cells in the small intestine. In terms of thinking, there is indeed another way to supplement NAD+, which is to find a way to supplement a certain substance so that it can synthesize NAD+ autonomously in the human body. There are three ways to synthesize NAD+ in the human body: Preiss-Handler pathway, de novo synthesis pathway and salvage synthesis pathway. Although the three ways can synthesize NAD+, there is also a primary and secondary distinction. Among them, the NAD+ produced by the first two synthetic pathways only accounts for about 15% of the total human NAD+, and the remaining 85% is achieved through the way of remedial synthesis. In other words, the salvage synthesis pathway is the key to the human body to supplement NAD+. Among the precursors of NAD+, nicotinamide (NAM), NMN and nicotinamide ribose (NR) all synthesize NAD+ through a salvage synthesis pathway, so these three substances have become the body's choice for supplementing NAD+. Although NR itself has no side effects, in the process of NAD+ synthesis, most of it is not directly converted into NMN, but needs to be digested into NAM first, and then participate in the synthesis of NMN, which still cannot escape the limitation of rate-limiting enzymes. Therefore, the ability to supplement NAD+ through oral administration of NR is also limited . As a precursor for supplementing NAD+, NMN not only bypasses the restriction of rate-limiting enzymes, but is also absorbed very quickly in the body and can be directly converted into NAD+. Therefore, it can be used as a direct, rapid and effective method to supplement NAD+. Expert Reviews: Xu Chenqi (Excellence and Innovation Center of Molecular Cell Science, Chinese Academy of Sciences, Immunology Research Expert) Cancer treatment is a problem in the world. The development of immunotherapy has made up for the limitations of traditional cancer treatment and expanded the treatment methods of doctors. Cancer immunotherapy can be divided into immune checkpoint blocking therapy, engineered T cell therapy, tumor vaccine, etc. These treatment methods have played a certain role in the clinical treatment of cancer. At the same time, this also makes the current focus of immunotherapy research on how to further enhance the effect of immunotherapy and expand the beneficiaries of immunotherapy.
Investigating the Great Possibility of Rare Ginsenosides as Drugs and Nutraceuticals
1. Introduction Rare ginsenosides, a group of dammarane triterpenoids that exist in low natural abundance, fuels a high concern from scholars recently, showing great potential as shining components in drugs and nutraceuticals. 2. The difference between primary ginsenosides and rare ginsenosides Ginsenosides are chiefly extracted from the plants of Araliaceae such as Panax ginseng, Panax notoginseng, and Panax quinquefolius. In light of their natural abundance, ginsenosides are usually divided into macro (primary) saponins (ginsenosides Rb1, Rg1, Re, Rd, etc.) and rare (secondary) ginsenosides (Rg5, Rk1, Rg3, etc). Relative to primary ginsenosides, rare ginsenosides are easy to be absorbed by human body, with much higher biological activity, membrane permeability and bioavailability. 3. The stereochemistry properties of rare ginsenosides The stereochemistry-driven difference in bioactivities is mostly focused on the 20(S/R)-Rg3 and 20(S/R)-Rh2 epimers. The stereochemistry properties confer rare ginsenosides with diverse bioactivities. Typically, the crucial factors that contribute to the efficacy of rare ginsenosises encompass the number of sugar molecules, sugar linkage and double bonds within C-17 side chain. For instance, the anti-tumor effect increased as the number of sugar moieties in a ginsenoside decreased. 4. Pharmacological activities of rare ginsenosides Rare ginsenosides serve as natural ligands for some specific receptors such as bile acid (FXR/TGR5), steroid hormone, estrogen, glucocorticoid, androgen, platelet adenosine diphosphate, which are determined to exert immunoregulatory and adaptogen-like effect, anti-aging effect, anti-tumor effect, as well as their effects on cardiovascular and cerebrovascular system, central nervous system, obesity and diabetes. 5. The impact of rare ginsenosides upon gut microbiota In addition to above-mentioned pharmacological activities, rare ginsenosides are also contributive to maintaining the homeostasis of gut microbiota. Under normal physiological condition, there is a dynamic balance in gut microbiota, which would be disrupted in the onset and development of certain disease. Rare ginenosides can restore the decreased abundance of certain affected microbiota, regulating the intestinal microecology to influence the physiological function of the host. 6. Conclusion By leverage of the stereochemistry properties, rare ginsenosides exhibit superior bioactivity, opening up new opportunities for the discovery and development of drugs and nutraceuticals. 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 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 consisting of Doctors and Masters. 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.
Delving into the Function of Ginsenoside Rh2 in the Develpoment of Breast Cancer
1. Introduction According to the 2020 report of World Health Organization (WHO), there are approximately 2.3 million cases with breast cancer worldwide. Breast cancer has emerged as one of the most malignant tumor in females with significant incidence rate. Although great progress has made in improving the cure rate of early-stage breast cancer in recent years, advanced breast cancer is still hard to be cured. How to reduce the risk of recurrence and metastasis of early-stage breast cancer as well as prolong the survival of patients with advanced breast cancer is still a challenge in the clinical treatment of breast cancer. Notably, ginsenoside Rh2 (GRh2) exerts prominent impacts on retarding the progression of breast cancer via strengthening the immune surveillance of natural killer (NK) cells, a kind of cytotoxic innate lymphocytes critical for tumor immune response. 2. The repressive role of GRh2 in the progression of breast cancer GRh2 hinders the growth, proliferation and metastasis of breast cancer. Simply put, the body weight and tumor volume of model mice are markedly reduced post treatment of GRh2 (10 mg/kg and 20 mg/kg). In addition, the proliferating rate of breast cancer cells is repressed by GRh2 in a dose-dependent manner (5, 10 and 20 mg/kg). Upon the treatment of GRh2 (20 mg/kg), the loss of lung capacity is obviously reduced and the lung metastases formed by MDA-MB-231 tumor cells are strikingly mitigated as well, with no apparent liver metastatic nodules. 3. The enhanced killing effect of NK cells on breast cancer cells following GRh2 treatment GRh2 exerts remarkable effects on retarding the progression of breast cancer via improving the killing ability of NK92MI cells. In a nutshell, the mRNA expression levels of killing mediators perforin and IFN-γ in NK92MI cell-breast cancer cell co-culture system are explicitly upregulated post GRh2 treatment. Strikingly, the reduced lung metastasis of breast cancer by GRh2 is almost counteracted upon the depletion of NK cells. Relative to that of the vehicle control, the amount of CD107a, a degranulation marker of NK cells, is overtly elevated in the presence of GRh2 (20 mg/kg), verifying the enhanced killing activity of NK cells on breast cancer. 4. The underlying molecular mechanism of GRh2 on potentiating the NK cell activity against breast cancer Breast cancer cells reduce the recognition by NKG2D through proteolytic shedding MICA mediated by ERp5 to escape NK cell surveillance. GRh2 interferes with the formation of soluble MICA (sMICA) by suppressing the expression of ERp5 to increase the contents of killing mediators from NK cells, thereby exerting striking effects on fighting against breast cancer. 5. Conclusion GRh2 potentiates the cytotoxic effect of NK cells and enhances the immune surveillance function of NK cells to fight against breast cancer, which may be a potent drug candidate for the prevention and treatment of breast cancer. Reference [1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660 [2] Yang C, Qian C, Zheng W, et al. Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer. Phytomedicine. 2024;123:155180. doi:10.1016/j.phymed.2023.155180 Product advantages of BONTAC ginsenoside Rh2 BONTAC is the first enterprise worldwide that can provide national mass production of ginsenosides (Rh2) by enzymatic synthesis, 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 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.