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NMNH, a novel and potent NAD precursor

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NMNH, a novel and potent NAD precursor

2024-08-27 10:00:38


Nicotinamide adenine dinucleotide (NAD) homeostasis is continuously compromised due to degradation by NAD-dependent enzymes. Supplementing NAD with the NAD precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. Some researchers reported the synthesis method of a reduced form of NMN, NMNH, and identified this molecule as a new NAD precursor for the first time, and confirmed that NMNH is more efficient than NMN and NR in increasing NAD levels and can reduce renal tubule size. Epithelial cells are damaged and their repair is accelerated. The results were published in "The FASEB Journal".

Enzymatic synthesis of NMNH: The high activity of NAD pyrophosphatase from Escherichia coli (EcNADD) is used to cleave NADH into NMNH and AMP.

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NMNH effectively increases NAD content:
In order to verify whether NMNH can effectively increase NAD content, different concentrations of NMN and NMNH were injected into the liver cells of AML12 mice. The results showed that at each concentration, NMNH increased the NAD level higher than NMN. At the same time, NAD levels increased significantly within 15 minutes using NMNH as a precursor, proving that NMNH is a faster precursor than NMN; and compared to NMN, NMNH increased NAD levels by 1.3-2.4 times. Being able to increase NAD levels from 5.2 times to 37 times proves that NMNH is a very effective precursor for NAD synthesis.
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In order to compare the effects of NMNH and NMN, the researchers injected PBS and 250 mg/kg of NMN and NMNH into C57BL/6N mice, respectively, and then conducted sequential blood sampling. The results showed that NMNH significantly increased NAD levels in the blood, to a much greater extent than NMN. NAD was measured on the collected tissues through the enzyme cycle method. The results showed that NMNH increased the NAD levels in various tissues, and the effect was higher than that of NMN. It had the most obvious effect on the liver and kidneys, with the liver increasing by more than 5 times and the kidneys increasing by more than 5 times. 2 times.

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NMNH protects renal tubular epithelial cells from damage:
Within the kidney, the proximal tubular epithelial cells are most susceptible to ischemic injury because it directly affects energy metabolism and places significant stress on NAD metabolism in the epithelium. Imbalances in metabolic pathways and a reduced ability to repair damaged epithelial processes predispose to kidney disease. Can increasing NAD levels by injecting exogenous NMNH effectively restore damaged epithelial cells? Administration of NMNH under normoxic conditions increased NAD content 5-fold, while at the same concentration, the effect of NMN was much lower than that of NMNH. Both NAD precursors significantly increased NAD content in renal tubular epithelial cells under hypoxic conditions, even above normoxic conditions. A similar situation was seen in cultured hepatocytes, where administration of NMNH also resulted in an increase in NAD-related metabolites to a much greater extent than NMN.
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NMNH was supplemented during the reoxygenation phase, and the expression of renal tubular injury marker KIM-1 was detected. Reoxygenation in TEC induced a sharp increase in KIM-1 expression, which decreased sharply after NMNH treatment, indicating that administration of NMNH can effectively and significantly reduce the damage to renal tubular epithelial cells during hypoxia and reoxygenation.

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