Rhamnose Acetamide Attenuates Glycation-Associated Skin Yellowness and Preserves Collagen-Positive Area in a Human Skin Explant Model

Glycation contributes to skin yellowing and deterioration of the dermal collagen matrix, highlighting the potential of antiglycation strategies to address these features of skin aging. This study investigated the protective effects of rhamnose acetamide (RA) against glycation-associated changes in human dermal fibroblasts and methylglyoxal (MGO)-treated human skin explants. Longitudinal facial colour measurements in 71 Korean women showed increased skin yellowness over approximately three years, underscoring the relevance of this visible skin change. In skin explants, topical RA partially attenuated MGO-induced yellowness and preserved the dermal collagen-positive area. The mean collagen-positive area was approximately 41% in RA-treated explants, compared with 28% in MGO-exposed vehicle explants and 51% in untreated explants. In fibroblasts, RA increased glyoxalase 1 (GLO1) expression and enzymatic activity, reduced high-glucose-induced advanced glycation end product (AGE)-associated immunofluorescence, and decreased the proportion of senescence-associated β-galactosidase-positive cells. Under MGO stress, RA partially restored intracellular ATP levels and increased sirtuin 1 activity at 200 μg/mL. RA also reduced reactive oxygen species and lipofuscin-associated accumulation under repeated ultraviolet A irradiation with MGO exposure between irradiations. Together, these findings demonstrate protective effects of RA against glycation-associated cellular and tissue changes in the experimental models studied, encompassing skin yellowness, dermal collagen preservation, and cellular senescence-related responses. These results highlight RA as a promising candidate for targeting glycation-associated features of skin aging.