Introduction and purpose: The skin in its function as a biological barrier of the human body protects against multiple environmental influences. In particular, sunlight triggers deleterious oxidative stress on in the skin. Adverse effects result in erythema, wrinkling, dryness, inflammation, autoimmune reactions, and pigment abnormalities. The generation of reactive oxygen species (ROS) is a common process occurring during various cellular reactions. An overproduction or inadequate processing of ROS within the skin manifests itself on a biomolecular level by lipid peroxidation, protein degradation, enzyme dysfunction and even DNA mutations/breakage. Accumulation of these effects over time has been associated with premature aging and photoaging. Sphingolipids are well known for their contribution and relevance for a proper skin barrier function. Besides that, special Sphingolipids can also have biochemical functions in regulation of cell growth, differentiation, and pathways in skin aging processes. Therefore, innovative bioactive Hydroxy-Ceramides were developed and screened for their biological activity.
Material & Methods: The efficacy of various Sphingolipid derivatives was analyzed using SimDerma® screening methods. For further investigation of anti-oxidative efficacy human epidermal keratinocytes (NHEK) were pre-incubated with test substances followed by UV irradiation (100 mJ/cm² UVB + 0.7 J/cm² UVA for ROS-formation measured via fluorescence intensity and 250 mJ/cm² UVB + 1.6 J/cm² UVA for analysis of DNA damage using a classical comet assay). For determination of cosmetic benefits an in vivo study with 16 panelists per test formulation, showing sun-stressed skin after summer period was performed. The molecule Hydroxybutyroyl-Phytosphingosine was topically applied in a suitable O/W vehicle emulsion at a concentration of 0.1% over a period of 8 weeks. Skin tone, texture parameters and skin density were monitored at different time points (start, 2 week, 4 weeks, 8 weeks).
Results: Screening of various Sphingolipid derivatives showed anti-oxidation and DNA repair effects. Hydroxybutyroyl-Phytosphingosine showed most promising efficacy and was further investigated in specific in vitro assays. A significant reduction in ROS formation and DNA damage after UV irradiation could be shown for this molecule. This efficacy finally results in improving sun-stressed skin conditions in vivo. Various texture parameters could be significantly improved after 4 and 8 weeks of topical application of Hydroxybutyroyl-Phytosphingosine. Skin roughness could be improved, skin density could be increased.
Discussion & Conclusion: Hydroxybutyroyl-Phytosphingosine showed promising anti-oxidative benefits in a broad screening approach with a special efficacy in DNA protection. Positive effects on sun-stressed skin could be shown in vivo. A re-balanced skin tone after summer stress might be due to an accelerated skin regeneration based on DNA protection. Overall, a protection from sun-induced premature aging for could be shown which marks Hydroxybutyroyl-Phytosphingosine as multifunctional product for holistic skin protection. Since DNA protection efficacy is not yet described for Sphingolipids, the exact working mechanism has to be further investigated.