The skin, as the largest and outermost barrier organ of the human body, is constantly exposed to hazardous environmental stress and simultaneously affected by psychological stress from day-to-day life. Exposure to excessive stressors will provoke overwhelming amounts of free radicals in the body and overcome the skin’s protective potential and leave the affected skin vulnerable to further damage. To protect and repair oxidative damages, the skin has its own antioxidant network and detoxification system, in which the thiol containing tri-peptide glutathione is considered playing a master role.

Reduced glutathione (GSH) is the most abundant low molecular weight antioxidant that maintains redox homeostasis by scavenging free radicals, reducing peroxides, and providing thiol-disulfide redox buffer through GSH/GSSG ratio. GSH also acts as a reservoir of antioxidant activity that boost the utilization and recycle of other cutaneous antioxidants such as vitamin C and E. Furthermore, GSH is critical for detoxification and eliminating electrophilic xenobiotics and participates repair of reversible oxidative damage of protein thiols through S-glutathionylation. More and more studies revealed versatile regulatory functions of glutathione in cell proliferation, apoptosis, immune functions, and skin melanogenesis. However, depleted glutathione levels in skin are associated with aging and oxidative stress from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS) and other free radical species. It is highly desirable to increase GSH level in skin to boost its resilience under stress and deliver skin benefits. However, topical application of glutathione with skincare product is quite challenging due to low stability and poor stratum corneum penetration of glutathione and controversial evidence of oral glutathione administration for skin benefits.

To solve these challenges, Unilever established skin protection platform over the last decade focusing the discovery of ‘Topical Glutathione Precursors’ technology, this highly versatile platform discovered a collection of biological active ingredients that could boost endogenous glutathione level in skin cells to protect itself against various stresses, such as UV rays and pollution.

Glutathione Amino acid Precursors (GAP), one of lead precursor bioactive composed with L-cystine, L-glutamine and glycine were successfully developed. Date from in vitro study showed significantly increased the GSH levels and GSH/GSSG ratio in normal human epidermal keratinocytes with presence of GAP, the protective effects of GAP against oxidative stress were superior to those of ascorbic acid. Topical application of a cosmetic formulation containing GAP significantly elevated the skin GSH/GSSG ratio in a clinical study. In a skin 3D model, GAP significantly improved model lightness and reduced melanin content and deposition under UVB challenge. RNA-seq analysis further revealed that GAP could restore UVB induced changes on expression of genes associated with pigmentation, inflammation, and aging. Transcriptomic aging clock analysis suggested that repeated UVB exposure caused a significant increase of biological age of the pLSE model, which could be attenuated by GAP treatment. The highlights were presented at the 25th World Congress of Dermatology Singapore 2023 and distinguished as ‘platinum feature poster’.

Reference:
1. A Novel Glutathione Boosting Blend Protects Skin Tone from UV and Oxidative Stress. Presented at the 24th World Congress of Dermatology 2019, Milan Italy
2. A Novel glutathione-boosting blend protects pollution induced cellular damage through autophagy regulation. Presented at the 25th World Congress of Dermatology 2023, Singapore
3. Time-course transcriptome profiles of 3D skin models under UVB exposure and intervention —roles of a glutathione precursor ingredients blend beyond anti-oxidation. Presented at the 25th World Congress of Dermatology 2023, Singapore
4. Glutathione amino acid precursors protect skin from UVB-induced damage and improve skin tone. JEADV 2024
5. Topical glutathione amino acid precursors protect skin against environmental and oxidative stress. JEADV 2024
6. Lysine carboxymethyl cystinate, a new skin brightening agent with unique mode of action investigated in vitro. Presented at the 2024 AAD annual meeting