The accumulation of oxidative damage and inflammation, induced by internal and external factors, represents a major mechanism underlying the aging of skin. Excessive reactive oxygen species (ROS) trigger mitogen-activated protein kinase (MAPK) pathways, upregulating matrix metalloproteinase (MMP) expression and facilitating extracellular matrix degradation. Although nicotinamide mononucleotide (NMN) and hyaluronic acid (HA) possess antioxidant and dermoprotective properties, their potential combinational effects remain largely obscure. This study evaluated the impact of NMN and HA co-treatment on ROS production, MAPK signaling, MMP-1 secretion, and type I collagen secretion in TNF-α-stimulated human epidermal keratinocytes. ROS levels were assessed via DCFDA assay, while MMP-1 and COL1A1 secretion were quantified using ELISA. Additionally, the regulatory effects on ERK, JNK, and p38 phosphorylation were determined by Western blot. Synergy prediction was analyzed using the SynergyFinder platform via Highest Single Agent and Loewe models. While NMN and HA individually attenuated TNF-α-induced ROS and MMP-1 levels, co-treatment provided superior suppression and exhibited combinational interactions at specific concentrations. These findings suggest that NMN and HA combination treatment effectively modulates oxidative stress and skin-aging-related responses by regulating ROS levels and MAPK signaling pathways.
Choi et al. (Wed,) studied this question.