**Background**
Nicotinamide adenine dinucleotide (NAD) is a critical cofactor and homeostatic regulator essential for cellular energy metabolism and redox balance. It serves as a key electron carrier, being reduced to NADH during the oxidation of organic substrates to indirectly generate ATP within the mitochondria. Due to its fundamental role in maintaining cellular health, NAD deficiency is linked to various metabolic disorders, including obesity, glucose intolerance, and non-alcoholic fatty liver disease. Furthermore, restoring NAD levels has shown potential in mitigating cellular stress and protecting tissues from injury. In this context, we will introduce a high-quality cofactor for biomedical research – NAD.
**Definition**
NAD (sodium) is an orally effective cofactor and homeostatic regulator with the molecular formula C21H26N7NaO14P2. It acts as a precursor to NADH and is utilized in research focusing on metabolic homeostasis and tissue repair.
**In Vitro and In Vivo Studies**
The NAD biological activity has been extensively characterized across various cell lines and animal models. In vitro studies demonstrate that NAD (sodium) is transported into NIH-3T3, SH-SY5Y, HeLa, HaCaT, HMEC, and RAW 264.7 cells, with an apparent Km of ~190 μM in NIH-3T3 cells. Specifically, NAD (sodium) (100 μM; 72 h) rescues FK866-induced cell death and replenishes intracellular NAD(P) levels in both NIH-3T3 and SH-SY5Y cells. Furthermore, treatment with 100 μM NAD (sodium) for 36 h was found to revert FK866-induced NAD autophagy in SH-SY5Y cells. In RAW264.7 cells, NAD (sodium) (0.5 mM) promotes M2 macrophage polarization, inhibits M1 polarization, and restores pro-angiogenic VEGF165 expression while inhibiting anti-angiogenic VEGF165b expression. Additionally, it restores reduced SRSF1 expression and inhibits increased SRSF6 expression in high glucose-exposed cells.
NAD in vivo studies have highlighted its therapeutic potential in cardiac recovery. In Kunming mice induced with diabetes and myocardial infarction, the administration of NAD+ (500 mg/kg/day; i.p.; daily for at least 28 days) significantly attenuated cardiac injury. This treatment restored cardiac NAD+ levels, reduced infarct size, and improved cardiac function, as evidenced by the reinstatement of ejection fraction (EF) and fractional shortening (FS) values. Moreover, it enhanced angiogenesis by increasing microvessel density and CD31/VEGF expression, while promoting M2 macrophage polarization in cardiac tissue. In conclusion, NAD is a versatile cofactor that supports cellular viability and promotes tissue regeneration in metabolic and cardiovascular disease models.
Keywords
NAD, 20111-18-6, β-DPN, β-NAD, β-Nicotinamide Adenine Dinucleotide, Endogenous Metabolite, 辅酶因子, 巨噬细胞M2极化诱导剂, Inhibitor, inhibitor, inhibit
References
[1] Rajman L, et al. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547.
[2] 20260224132312.pdf
[3] Ruszkiewicz J, et al. NAD+ Acts as a Protective Factor in Cellular Stress Response to DNA Alkylating Agents. Cells. 2023;12(19):2396. Published 2023 Oct 2.
[4] Jiao L, et al. NAD+ attenuates cardiac injury after myocardial infarction in diabetic mice through regulating alternative splicing of VEGF in macrophages. Vascul Pharmacol. 2022;147:107126.