Research on Formulation Development for the Application of Exogenous NAD⁺
Nicotinamide adenine dinucleotide (NAD⁺) is an essential metabolic coenzyme in human cells. It participates in multiple physiological processes, including cellular redox reactions, sirtuin activation, autophagy regulation, and mitochondrial energy metabolism. The intracellular NAD⁺ level fluctuates along with cellular status. As a key hydrolase, CD38 mediates the degradation and consumption of NAD⁺, which reduces the actual utilization efficiency of exogenously supplemented NAD⁺.

In Vitro Cell Studies
In vitro cell studies have revealed that the sole addition of exogenous NAD⁺ triggers a feedback upregulation of CD38 expression in cells, accelerating NAD⁺ degradation and limiting its intracellular functions. In contrast, a combined formulation of quercetin and glycyrrhetinic acid suppresses CD38 expression, reduces NAD⁺ breakdown, improves the bioavailability of exogenous NAD⁺ in human dermal fibroblasts, and elevates the cellular NAD⁺/NADH ratio.
A Series of Assays Using an In Vitro Human Fibroblast Model
A series of assays based on the in vitro human fibroblast model demonstrate that increased intracellular NAD⁺ levels positively modulate sirtuin protein activity and promote the expression of autophagy-related genes, which helps preserve mitochondrial structure and energy metabolic function. In the UV-challenged in vitro model, this combination alleviates DNA damage, modulates the expression of matrix metalloproteinases, and sustains cell viability. In the NAD⁺-depleted cell model, exogenous NAD⁺ combined with the quercetin–glycyrrhetinic acid complex improves fibroblast proliferation and migration, facilitating cellular repair after injury. Meanwhile, co-administration of the two agents synergistically downregulates the release of certain inflammatory mediators in an in vitro macrophage inflammation model.
This study provides in vitro theoretical support for the application of exogenous NAD⁺ raw materials in skincare. It should be noted that all experiments in this research are in vitro cell studies; animal and human skin tests have not yet been performed. The transdermal penetration of NAD⁺ and its in vivo effects in humans remain to be further verified. The findings do not represent the efficacy of finished skincare products and serve only as a scientific reference for formulation development.
References
Kang S, Park J, Cheng Z, et al. Novel Approach to Skin Anti‑Aging: Boosting Pharmacological Effects of Exogenous Nicotinamide Adenine Dinucleotide (NAD⁺) by Synergistic Inhibition of CD38 Expression[J]. Cells, 2024, 13(21):1799.
*Special note - This article is for informational purposes only and cannot replace a doctor's treatment diagnosis and advice. It should not be regarded as a recommendation or proof of efficacy of the medical products involved. If it involves disease diagnosis, treatment, and rehabilitation, please be sure to go to a professional medical institution to seek professional advice.
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