## 1 Introduction
Analogous chemistry is seen with its phosphorylated derivative, nicotinamide adenine dinucleotide phosphate (NADP\({}^{+}\) to NADPH). Traditionally, NAD\({}^{+}\) and its derivatives function as coenzymes for dehydrogenases and oxidoreductase, playing crucial roles in fundamental energy metabolism processes, such as glycolysis, the citric acid cycle, and mitochondrial (MT) electron transport. In addition to its classical functions, NAD\({}^{+}\) also serves as a vital substrate for signaling enzymes, e.g., poly [adenosine diphosphate (ADP)-ribosyl] polymerases, sirtuins (SIRTs), and ADP-ribosyl-transferases. These enzymes are referred to as \"NAD\({}^{+}\) consumers\" [17; 18; 19; 20; 21]. As is classically understood, as well as from recent discoveries, NAD\({}^{+}\) is seen as a crucial and abundant metabolite present in all mammalian cells. It participates in a wide array of cellular mechanisms, including essential processes such as metabolism and cell signaling that are vital for survival. This notwithstanding, the limited presence of NR in food sources (with some quantitative studies available), together with the challenges associated with obtaining significant quantities of pure NR as a dietary supplement, have hindered research on the effects of NR on cells and tissues [22; 23]. Nevertheless, recently, synthesis techniques for producing NR have been notably advanced, resulting in new and refined approaches [24]. However, these new technologies were developed for cell-based investigations and animal feeding tests, not for human consumption [25; 26]. Non-classical roles also exist for NAD\({}^{+}\). For example, NAD\({}^{+}\) activates SIRTs and supports the MT response to unfolded proteins. Pursuing these non-classical roles, NAD\({}^{+}\) metabolism is seen to be involved in an extensive spectrum of pathologies, including cancer, neurodegenerative disorders, cardiomyopathy, obesity, diabetes, and even hearing loss [4; 27; 28; 29; 30; 31]. In many tissues (e.g., brain, muscle, skin, liver, pancreas, and adipose tissue), the level of NAD\({}^{+}\) decreases with age. A separate decrease in the NAD\({}^{+}\)/NADH ratio affects the cellular redox state, highlighted by anaerobic glycolysis and oxidative phosphorylation (OXPHOS). This decreases, it is thought, the capacity of cells to generate adenosine triphosphate (ATP) [32]. Consequently, healthy aging and longevity are thought to be related to NAD\({}^{+}\) metabolism, mainly through NR and NMN, two essential and well-studied NAD\({}^{+}\) derivatives. One argument for NAM-related dietary supplements is that these can have prophylactic and therapeutic impact on functional decline, improving age-associated neurodegenerative, cardiovascular (CV), and metabolic diseases and conditions, and promoting the beneficial effects of calorie restriction (CR) [4; 33; 34; 35; 36]. As a precursor of NAD\({}^{+}\), NR is also proposed to be important in regulating oxidative stress (OXS), inhibiting oxidative injury and inflammatory response, with beneficial effects in the treatment of sepsis [37], systemic lupus erythematosus (SLE) [38], and necrotizing enterocolitis (NEC) [39]; furthermore, NR showed significant protective effect on lung injury caused by paraquat (PQ) in mice [40]. Separately, sepsis-caused multiple organ failure is the major risk of morbidity and mortality in intensive care units. In experimental models of mouse sepsis induced by lipopolysaccharideacharide (LPS) injection, feces injection in peritoneum, or by cecal ligation and puncture, NR inhibited plasma high mobility group box 1 (HMGB1) release, OXS, and tissue infiltration, increased endogenous antioxidant ability, prevented lung and heart injury, and improved survival [37; 41]. This is mediated via NAD\({}^{+}\)/SIRT1 signaling. NR could be a potential adjuvant for SLE treatment. In vitro testing in monocytes from patients with SLE showed that NR restricted autophagy (ATG) and attenuated interferon-beta (IFN-\(\beta\)) release in an NAD\({}^{+}\)-dependent manner, but also through inosine signaling [38].