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.
When applied to cultured cells, the NMNH is shown to be more efficient than NMN as it was able to “significantly increase NAD+ at a ten times lower concentration (5 µM) than that needed for NMN”. Moreover, NMNH shows to be more effective , as at 500 µM concentration, it achieved “an almost 10-fold increase in the NAD+ concentration, while NMN was only able to double NAD+ content in these cells, even at 1 mM concentration.”.
Interestingly, NMNH also appears to act quicker and has a longer-lasting effect compared to NMN. According to the authors, NMNH induces a “significant increase in NAD+ levels within 15 minutes”, and “NAD+ steadily increased for up to 6 hours and remained stable for 24 hours, while NMN reached its plateau after only 1 hour, most likely because the NMN recycling pathways to NAD+ had already become saturated.”.
The main methods of NMNH powder preparation include extraction, fermentation, fortification, biosynthesis and organic matter synthesis. Compared with other preparations, the whole enzyme becomes the mainstream method owing to the advantages of pollution free, high level of purity and
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 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.
Nicotinamide adenine dinucleotide (NAD+ ) homeostasis is constantly compromised due to degradation by NAD+ -dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
First, inspect the factory. After some screening, NMNH 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 NMNH 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 NMNH cannot be guaranteed, the remaining substances are likely to exceed the relevant standards. As the attached certificates demonstrates that the NMNH 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.
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.
Introduction Ginsenoside Rh2, one protopanaxadiol (PPD)-type rare ginsenoside in Panax ginseng, is uncovered to possibly have broad-spectrum pharmacological activity in diversified tumors. It is utilized as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer, which has been a research hotspot in recent years. Current states on cancer therapies Cancer has emerged as the second largest cause for death across the world, with approximately 9.6 million cancer-related deaths in 2018, in accordance with the statistical report by World Health Organization (WHO). Radiotherapy, chemotherapy and surgery are the preferred option for cancer, whose efficacy is however limited by the tumor relapse and drug resistance, requiring a patch such as adjuvant drugs to fix the bug. For anticancer treatment, over 60% of the approved and pre-new drug application candidates are natural products or synthetic molecules based upon natural product molecular skeletons. Strikingly, ginsenosides act as a promising therapeutic target by virtue of its pharmacological activities such as immune adjustment, anti-tumor, anti-oxidation, and protection of the heart and cerebral vessels. 20(S) ginsenoside Rh2 vs. 20(R) ginsenoside Rh2 There are two stereoisomeric forms of ginsenoside Rh2, namely 20(S) ginsenoside Rh2 and 20(R) ginsenoside Rh2. Relative to the (20R) ginsenoside Rh2, (20S) ginsenoside Rh2 has higher cytotoxic activity towards cancer cells. In a previously reported study, the half maximal inhibitory concentration values of 20(S) ginsenoside Rh2 and 20(R) ginsenoside Rh2 in A549 cells are 45.7 and 53.6 µM, respectively. The underlying mechanisms of ginsenoside Rh2 against tumor Mechanically, the anti-tumor effects of ginsenoside Rh2 are realized by enhancing the body’s immune activity to regulate microenvironment, inhibiting differentiation, angiogenesis, proliferation, invasion, and metastasis of tumor cells, inducing the apoptosis, cell cycle arrest, autophagy, superoxide and reactive oxygen species, and reversing the drug resistance via regulating a series of important tumor-related signaling pathway. For instance, ginsenoside Rh2 can activate CD4+ and CD8a+ T lymphocytes, promote their invasion, and enhance the killing effect of lymphocytes on B16-F10 melanoma cells in a concentration-dependent manner. Besides, the number of tumor cells in the G0/G1 phase is increased significantly post treatment with ginsenoside Rh2 and 5-FU, by which the expansion and migration of tumor cells are effectively hampered. Additionally, the ginsenoside Rh2 downregulates the levels of drug-resistance-related genes (eg. MRP1, MDR1, LRP and GST), making colorectal cancer cells more sensitive to 5-FU. Conclusion Ginsenoside Rh2 plays multifunctional roles in both tumor treatment and tumor microenvironment immunomodulation, which may become a promising choice of medication for patients with tumors in the future. Reference [1] Xiaodan S, Ying C. Role of ginsenoside Rh2 in tumor therapy and tumor microenvironment immunomodulation. Biomed Pharmacother. 2022;156:113912. doi:10.1016/j.biopha.2022.113912 [2] Yang L, Chen JJ, Sheng-Xian Teo B, Zhang J, Jiang M. Research Progress on the Antitumor Molecular Mechanism of Ginsenoside Rh2. Am J Chin Med. Published online January 31, 2024. doi:10.1142/S0192415X24500095 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. BONTAC holds no responsibility for any claims, damages, losses, expenses, costs or liabilities resulting or arising directly or indirectly from your reliance on the information and material on this website.
1. Introduction Diabetic peripheral neuropathy (DPN) is one of the most frequent complications of diabetes, ans also a major cause of foot ulcers, disability, and eventual amputation. With the prolongation of the diabetes, about 50% of people with diabetes will eventually develop DPN. Notably, supplementing NAD+ precursors could alleviate DPN symptoms by increasing the NAD+ level and activating the sirtuin-1 (SIRT1) protein. 2. The reversal effect of NAD+ precursors on DPN In vitro, the Dorsal Root Ganglion neurons (DRGs) isolated from diabetic mice are exposed to the NAD+ precursor Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN). It is found that the NAD+ level, the SIRT1 protein, and the deacetylation activity are elevated, followed by the boosted neurite growth, the improved nerve function, and the reversal of IENFD loss. In vivo, supplement of NMN or NR also offsets the neuropathy in C57BL6 mice induced by streptozotocin (STZ) or high fat diet (HFD), as manifested by the improved sensory function, normalized nerve conduction velocities, and restored intraepidermal nerve fibers. 3. The increase of neurite length in a SIRT1-dependent manner post the addition of NMN/NR SIRT1, one of the most unique NAD+ consuming enzymes, can protect against DPN when activated, which may attribute to the improved mitochondrial function and energy homeostasis. Apart from these, SIRT1 activity in the nucleus can deacetylate the transcriptional and co-transcriptional factors that regulate glucose homeostasis and fat oxidation. The activation of SIRT1 is critical for axonal regeneration. NMN/NR treatment or transfection with SIRT1 overexpression vector can directly facilitate the neurite growth in cultured DRG neurons, which however is hindered by the SIRT1 inhibitor EX527, hinting the significance of SIRT1. 4. The association of SARM1 with NMNAT2 in axonal degeneration of DPN Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) controls the axonal degeneration and regeneration via a well-regulated system comprising NAD+ and NMN. NAD and NMNAT2 can boost vesicular glycolysis and axonal transport to maintain the axonal health. The mitochondrial localization of SARM1 complements the coordinated activity of NMNAT2 that promotes axonal survival. 5. Conclusion Supplementing NAD+ precursors may be a promising approach for the treatment of DPN. A SARM1 inhibitor coupled with either NR or NMN may be more effective than a single agent alone in preventing or treating DPN. Reference Chandrasekaran K, Najimi N, Sagi AR, et al. NAD+ Precursors Reverse Experimental Diabetic Neuropathy in Mice. Int J Mol Sci. 2024;25(2):1102. Published 2024 Jan 16. doi:10.3390/ijms25021102 BONTAC NMN and NR BONTAC has dedicated to the R&D, manufacture and sale of raw materials for coenzyme and natural products since 2012, with self-owned factories, over 160 global patents as well as strong R&D team consisting of Doctors and Masters. Different from the traditional chemical synthesis and fermentation industry, BONTAC has advantages of green low-carbon and high-value-added biosynthesis technology. Both the precursors NMN and NR are available in BONTAC. The high purity and stability 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.