Antioxidant and membrane-protective effects of the 3-O-ethyl ascorbic acid-cannabigerol system on UVB-irradiated human keratinocytes

The lack of effective protection against UVB radiation, that severely disrupts the metabolism of keratinocytes, underlines the search for bioactive compounds that would provide effective protection without causing side effects. Therefore, the aim of the study has been to assess the effect of two compounds, that are different in terms of structure and properties: 3-O-ethyl ascorbic acid-EAA (a stable derivative of vitamin C) and cannabigerol-CBG, used separately or concurrently, on the metabolism of keratinocytes previously exposed to UVB. The obtained results indicate diverse, yet mutually reinforcing localization of the tested compounds, both within the membrane structures and cytosol. When used concurrently, EAA + CBG effectively prevent modifications of the structure of cell membranes, particularly the increase in their fluidity and permeability caused by UVB. It promotes cell survival and enhances the expression of membrane transporters, especially BCRP. Moreover, the concurrent use of both compounds, by reducing the level of ROS and regulating the expression of both Nrf2 activators (p62, MAPK) and inhibitors (Keap1, Bach1, PAGM5), supports the antioxidant efficiency of cells, visible in the increased activity of antioxidant enzymes (SOD1/2, CAT) and the effectiveness of GSH- and Trx-dependent antioxidant systems. Consequently, oxidative modifications of lipids (assessed as 4-HNE and isoprostanes) and proteins (measured as 4-HNE-protein adducts and carbonyl groups) are reduced. The tested compounds also reveal anti-inflammatory effects by modifying the expression of the activator (p62) and inhibitors (IKKα, IKKβ) of NFκB. The observed EAA + CBG effect in preventing changes in the structure and functionality of keratinocyte membranes, maintaining redox balance, and mitigating inflammatory effects caused by UVB provides the basis for further research.