Table 1.
Overview of experimental studies on NMN conducted following the second wave of NAD + research
| Pre-clinical experiment results | |||
|---|---|---|---|
| Model/Animal | Treatment regimen | Outcomes | Reference |
| C57BL/6 mice | 100 or 300 mg/kg/d (PO) for 12 months | Inhibited weight gain; reduced physiological decline; improved insulin sensitivity and lipid distribution; and improved eye function, physical activity, energy metabolism, and mitochondrial function in skeletal muscle | [9] |
| Namptflox/flox mice | 100 or 300 mg/kg/d (PO) for 12 months | Enhanced hippocampal NAD + levels and maintained the nerve stem/progenitor cell pool | [13] |
| C57BL/6 mice | 300 mg/kg (PO) for 8 weeks | Reduced vascular oxidative stress and attenuated age-related endothelial dysfunction and arterial stiffness | [14] |
| SIRT1-iKO, EglN1 KO, SIRT1-Tg mice | 500 mg/kg/d (IP) for 1 week | Enhanced oxidative metabolism in the mitochondria of skeletal muscle in aged mice | [15] |
| High-fat diet-induced mouse model of diabetes | 500 mg/kg/d (IP) for 7–10 days | Restored NAD + levels and enhanced insulin sensitivity/insulin secretion to improve glucose tolerance | [18] |
| Age-induced mouse model of diabetes | 500 mg/kg/d (IP) for 11 days | ||
| Friedreich ataxic cardiomyopathy mice | 500 mg/kg (IP), twice a week, for 4–5 weeks | Improved diastolic function and normalized systolic function, improved cardiac energy production and utilization, reduced overall energy expenditure, and improved cardiac glucose metabolism | [19] |
| Ischemia–reperfusion or cisplatin-induced mouse models of acute kidney injury and SIRT1± mice | 500 mg/kg/d (IP) for 4 days | Restored SIRT1 activity and NAD + levels in mouse kidneys and protected mice from ischemia–reperfusion or cisplatin-induced acute kidney injury | [23] |
| Rod cell-specific Nampt knockout mice | 150 mg/kg (IP) for 4 weeks; 300 mg/kg (IP) for 10 days | Restored NAD + levels, glycolysis, and mitochondrial function in photoreceptor cells; prevented photoreceptor degeneration; restored vision; and protected the retina from light damage | [24] |
| C57BL/6 mice with retinal detachment | 250 mg or 500 mg/kg/d (IP) for 7 days | Increased NAD + levels and SIRT1 expression; reduced photoreceptor cell death; reduced retinal inflammation; and inhibited oxidative stress | [25] |
| C57BL/6 mice fed a fructose-rich diet | 500 mg/kg (IP) single dose | Inhibited inflammation and improved insulin secretion | [26] |
| SIRT2tg mice and BubR1H/+ mice | 500 mg/kg/d (IP) for 7 days | Increased NAD + and BubR1levels and prolonged the lifespan of SIRT2tg/BubR1H/H mice | [27] |
| C56BL6/J female mice | 500 mg/kg/d (IP) for 21 days | Reduced retroperitoneal fat mass, increased quadriceps muscle weight, improved glucose tolerance, and lowered hepatic and plasma triglyceride levels | [28] |
| C56BL6/J mice fed a high-fat diet | 500 mg/kg/d (IP) for 18 days | Increased liver NAD + levels, decreased liver triglyceride levels, improved glucose tolerance, and decreased body weight | [29] |
| SIRT1-iKO mice | 400 mg/kg/d (PO) for 2 months | Restored SIRT1 activity, increased capillary formation and blood flow in skeletal muscle, and improved endurance and positive muscle response to exercise | [30] |
| C57BL/6 mice | 500 mg/kg/d (IP) for 14 days | Restored the neurovascular mRNA expression in aged mice to the levels seen in young mice and improved microvascular endothelial function and the neurovascular coupling response in the brain | [31] |
| C57BL/6 mice | 500 mg/kg/d (IP) for 14 days | Attenuated the cerebrovascular endothelial dysfunction caused by aging, improved the neurovascular coupling response in elderly mice, and restored NAD + levels and mitochondrial energy in microvascular endothelial cells in the aging brain | [32] |
| Heart-specific Ndufs4 knockout mice | 500 mg/kg/d (IP) for 3days | Reduced the acetylation of cardiac mitochondrial proteins and enhanced the sensitivity of mitochondrial permeability transition | [33] |
| Mouse model of cardiac ischemia–reperfusion injury model and Sirt3−/− Mice | 1 mM via perfusion, single dose | Protected the heart by stimulating glycolytic ATP synthesis during ischemia and by enhancing acidosis during reperfusion | [34] |
| Heart-specific KLF4-deficient mice | 500 mg/kg/d (IP) for 3 days | Restored normal mitochondrial acetylation and protected the heart, improved mitochondrial fatty acid oxidation, preserved mitochondrial ultrastructure; and reduced cell death in stress-overloaded hearts | [35] |
| Mouse model of cardiac fibrosis | 500 mg/kg (IP) every 3 days from 5 days before surgery to 4 weeks after surgery | Reduced cardiac dysfunction, fibrosis, and hypertrophy | [36] |
| Adipocyte-specific Nampt-knockout (ANKO) mice | 500 mg/kg (PO) single dose | Partially attenuated impairments in physical activity | [37] |
| Mouse model of cerebral ischemia | 31.25–50 mg/kg (IP) single dose | Protected hippocampal CA1 neurons from ischemic death and preserved neuronal function | [38] |
| Collagenase-induced mouse model of cerebral hemorrhage | 300 mg single dose via tail vein injection; 300 mg/kg/d for 7 days | Prevented acute brain injury, reduced brain cell death and oxidative stress, inhibited neuroinflammation and pro-inflammatory factor levels, and activated the Nrf2/HO-1 signaling pathway | [39] |
| SIRT3-KO mice | 62.5 mg/kg (IP) single dose | Improved hippocampal mitochondrial NAD + levels, inhibited mitochondrial protein acetylation and ROS levels, and attenuated cerebral ischemic injury | [40] |
| Alzheimer's disease mouse model (AD-Tg mice) | 100 mg/kg every other day (SC) for 28 days | Reduced the level of amyloid precursor protein and improved mitochondrial function | [41] |
| Ca1-specific Nampt-knockout mice | 300 mg/kg/d (PO) for 3 weeks | Enhanced the expression of Cask in the hippocampus of older mice to attenuate age-related cognitive impairment | [42] |
| C57BL/6 mice | 250 mg or 500 mg/kg/d (IP) for 24 h, 3 d, and 7 d | Reduced photoreceptor cell death, inhibited retinal inflammation, and reduced oxidative stress | [43] |
| UVB-irradiated C57BL/6 mice | 500 mM and 5 μL/eye (subconjunctival injection) for 2 days | Prevented corneal tissue injury and endothelial cell apoptosis in mice | [44] |
| Mouse model of retinal ischemia–reperfusion injury | 500 mg/kg/d (IP) for 4 days | Prevented retinal dysfunction and reduced retinal inflammation | [45] |
| Diabetic db/db mice | 500 mg/kg/d (IP) for 14 days | Improved the histopathology associated with diabetic nephropathy, increased Nampt expression, provided long-lasting renal protection, and improved the survival rate | [46] |
| Mouse model of doxorubicin-induced focal glomerulosclerosis | 500 mg/kg/d (IP) for 14 days | Decreased urinary albumin levels; alleviated glomerular sclerosis; increased the concentration of NAD + ; enhanced Sirt1 expression and decreased Claudin-1 expression; and upregulated histone methylation and Dnmt1 expression] | [47] |
| C57BL/6 mouse model of sepsis | 500 mg/kg (IP) single dose | Increased NAD + levels in multiple organs and decreased serum lactate levels, oxidative stress, inflammation, and caspase3 activity | [48] |
| Mouse model of sepsis-associated encephalopathy | 500 mg/kg (IP) single dose | Inhibited the hippocampal inflammatory response; alleviated memory impairment; reduced the apoptosis of hippocampal cells; inhibited microglial activation; and prevented hippocampal neuroinflammation and oxidative stress | [49] |
| SIRT2, NMNAT1, and NMNAT3 transgenic mice | 2 g/L (PO) for 4 weeks; 400 mg/kg (PO) single dose | Improved fertility by restoring NAD + levels and restored oocyte quality, embryo development, and live birth rates | [50] |
| ICR female mice | 200 mg/kg/d (IP) for 14 days | Increased the number of ovulations in old mice, enhanced the meiotic and fertilization ability of aging oocytes, and restored mitochondrial function to inhibit ROS-induced apoptosis in aging oocytes | [51] |
| Prx1-Cre mice ColA1flox−stop−flox−SIRT1 mice | 300 mg/kg/d (IP) for 3 months | Promoted MSC expansion in adult mice, stimulated osteogenesis in older mice, inhibited fat generation in older mice, and protected mouse bones from aging and radiation-induced damage | [52] |
| Hemorrhagic shock model in Long-Evans rats | 400 mg/kg/d (PO) for 5 days | Significantly reduced inflammation, improved cell metabolism, and promoted survival after hemorrhagic shock | [53] |
| Hypoxia-induced mouse model of adipose tissue fibrosis | 500 mg/kg/3d (IP) for 4 weeks | Restored the impaired NAD + /SIRT1 axis; inhibited hypoxia-induced HIF-1α activation; and alleviated hypoxia-induced adipose fibrosis and inflammation | [54] |
| HIV-1-infected humanized mice | 300 mg/kg/d (PO) for 24 days | In combination with cART treatment, significantly increased the percentage of CD4 + T cells in HIV-infected huPBL mice | [55] |
IP: intraperitoneal; SC: Subcutaneous; PO: per oral