Lysine Carboxymethyl Cysteinate (LCC) Protects the Epidermis from UVB-Induced Barrier Damage Through the Activation of Autophagy.

Lysine carboxymethyl cysteinate (LCC) has been identified as a glutathione (GSH) precursor for the use of cosmetic products, providing a defense against oxidative stress by elevating GSH levels, and mitigating UVB-induced pigmentation and barrier disruption. In this study, the protective efficacy of LCC on epidermal barrier integrity under UVB irradiation was systematically evaluated and its underlying mechanisms were investigated. Results from the UVB-exposed 3D living skin equivalent model (LSE) indicated that LCC effectively restored UVB-induced reductions in epidermal living cell thickness by 9.67%. In addition, LCC markedly increased the expression of key biomarkers related to cornified envelope (CE) formation and skin hydration, including transglutaminase 1, involucrin, loricrin and aquaporin 3 by 104.80%, 121.67%, 218.63% and 388.39%, respectively, compared with the UVB group. Transcriptomics analysis in human primary keratinocytes further revealed that LCC regulated multiple biological functions, including glutathione synthesis pathway, oxidation response, inflammatory process, and notably autophagy. After confirming LCC's potential in boosting autophagy-associated gene expression (p-value < 0.05) and autophagy activity (p-value < 0.01) in keratinocytes, functional validation in the same model confirmed that LCC counteracted UVB-induced suppression of genes involved in barrier formation, particularly those associated with CE development and autophagy, while these protective effects were abolished by chloroquine, an autophagy inhibitor. Findings from the UVB-exposed LSE model further substantiated this mechanism. Collectively, these results demonstrate that LCC safeguards the epidermis from UVB-induced cornification abnormalities through the activation of autophagy.