Orally Delivered Hyaluronic Acid Tetrasaccharide Improves Skin Barrier Function in UVB-Irradiated Mice: A Bioactive Approach for Cosmetic and Nutritional Applications

Hyaluronic acid (HA), which is present in various foods, has been the subject of various claims about its ability to relieve dry skin. In this study, the intestinal absorption of hyaluronic acid tetrasaccharide (HA4) and its ability to protect the skin from UV after oral administration were compared with those of high-molecular-weight HA. Intestinal absorption was evaluated by the Caco-2 cell monolayer mem-brane permeability assay. HA4 permeated the Caco-2 monolayer, reaching 2.67 µg/cm2 after 120 min, whereas HA did not. HA or HA4 was orally administered to UVB-irradiated mice, and the effects were evaluated using transepidermal water loss (TEWL), water content of the stratum corneum (SC), and epidermal thickness. HA4 permeated the Caco-2 monolayer. On day 26, TEWL significantly increased by 17.5 ± 3.1 g/m2/h in the Control group but only 8.0 ± 1.7 g/m2/h in the HA4 group compared to the Normal group, but no significant difference was observed. Water content of SC decreased by 25.7 ± 1.5 arbitrary units (a.u.) in the Control group; the decrease was attenuated in the HA4 group (17.5 ± 0.7 a.u.) (p < 0.05 vs. Control). On day 28, epidermal thickness reached 69.5 ± 10.8 µm in the Control group and was significantly lower in the HA4 group (43.5 ± 5.1 µm) (p < 0.01 vs. Control). These findings indicate that orally administered HA4 is efficiently absorbed and significantly attenuates UVB-induced skin barrier impairment, suggesting its promise as a functional food ingredient for improving dry skin.