Objective: This study aimed to investigate the synergistic effects of Ergothioneine (EGT) and Tyrosine-Arginine Peptide (TAP) in promoting β-endorphin production in the skin, aiming to alleviate stress-induced dermatological disorders.

Method: An optimal ratio between EGT and TAP for β-endorphin stimulation was ascertained through cell experiments using human dermal fibroblasts and immortalized human keratinocytes. These cells were treated with cortisol to induce stress-related conditions. β-endorphin content was measured following treatment with various EGT-TAP ratios. Additional gene expression analysis was conducted to observe the regulatory effects of the combination on key skin health indicators, using specific primers and qPCR methods.

Results: The combination of EGT and TAP displayed a significant synergistic effect on β-endorphin production, with the optimal ratio identified as 9:1. This ratio resulted in a 175.75% and 190.20% increase in β-endorphin generation compared to individual EGT and TAP treatments, respectively. The EGT-TAP combination also mitigated cortisol-induced disruptions in gene expression, positively affecting the expression of extracellular matrix proteins and mitigating the negative effects of stress on skin cell models.

Conclusion: The combined administration of EGT and TAP at a 9:1 ratio significantly boosts β-endorphin levels and beneficially regulates gene expression under stress-induced conditions in skin cells. This synergy presents a novel and effective approach to enhance skin health and counteract the detrimental impacts of stress, offering a promising avenue for the development of advanced dermatological treatments.