Ergothioneine, collagen peptides, and sodium hyaluronate ameliorate facial skin aging via modulating oxidative stress, inflammation, and extracellular matrix homeostasis.

BACKGROUND: Skin aging involves intrinsic chronological aging and extrinsic photoaging, characterized by impaired barrier function, extracellular matrix (ECM) degradation, and chronic inflammation. METHODS: This study evaluated anti-aging efficacy and mechanisms of ergothioneine (EGT), collagen peptides (CP) and sodium hyaluronate (NaHA) using an ex vivo human skin model and a clinical trial. RESULTS: Ex vivo results showed that the EGT+CP+NaHA triple combination (TC) attenuated UV-induced epithelial thinning and collagen fiber disruption. Mechanistically, TC enhanced antioxidant capacity by up-regulating Nrf2 and SOD2 expression, modulated the senescence-associated secretory phenotype (SASP) via restoring TGF-β1 and suppressing IL-1α, IL-6, and MMP1 levels, and preserved ECM integrity by reversing reductions in collagen I, III, IV, VII, XVII, and hyaluronic acid (HA) contents. Clinically, oral TC to Chinese women improved skin hydration, elasticity, and barrier function, while reducing the number, depth, area, and volume of crow's feet wrinkles, nasolabial folds and marionette lines. CONCLUSION: These findings demonstrate that TC exerts multifaceted anti-aging effects by targeting oxidative stress, inflammatory pathways, and ECM homeostasis, providing a scientific basis for the development of novel oral nutricosmetics for facial skin anti-aging.