Glutathione amino acid precursors protect skin from UVB-induced damage and improve skin tone.

Background: UV radiation exposure causes skin irritation, erythema, darkening and barrier disruption by inducing oxidative stress and inflammation. Glutathione, a master antioxidant, plays an important role in the antioxidant defence network of the skin.

Objective: This study aimed to assess the in vitro protective effects of the glutathione amino acid precursors blend (GAP) on transcriptomic and phenotypic endpoints against UVB-induced challenges.

Methods: Normal human epidermal melanocytes (NHEMs) were exposed to GAP, ascorbic acid (AA) and its derivatives. Viability was assessed using the CCK8 method. Melakutis®, a pigmented living skin equivalent (pLSE) model, underwent repeated 50 mJ/cm UVB irradiation with or without GAP treatment. Images of the model were captured with consistent camera parameters, and the model's light intensity was measured using a spectrophotometer. Melanin content was determined by measuring absorbance at 405 nm. Confirmation of melanin deposition and distribution was achieved through Fontana-Masson staining. Transcriptomic analysis was conducted using RNA sequencing (RNA-Seq), and a machine learning approach was employed for transcriptomic aging clock analysis.

Results: In NHEMs, all tested compounds exhibited over 85% viability compared to the vehicle control, indicating no heightened risk of cytotoxicity. Notably, GAP demonstrated greater efficacy in inhibiting melanin production than AA derivatives at equivalent concentrations. In pLSE models, GAP notably enhanced model lightness, and reduced melanin content and deposition following the UVB challenge, whereas AA showed minimal impact. GAP effectively counteracted UVB-induced alterations in gene expression linked to pigmentation, inflammation and aging. Moreover, recurrent UVB exposure substantially elevated the biological age of pLSE models, a phenomenon mitigated by GAP treatment.

Conclusions: In NHEMs, GAP exhibited enhanced effectiveness in inhibiting melanin production at identical tested doses in comparison to AA derivatives. Noteworthy protective effects of GAP against UVB irradiation were observed in the pLSE models, as evidenced by skin pigmentation measurements and transcriptomic changes.