The Anti-Inflammatory Action of Cannabigerol Accompanied by the Antioxidant Effect of 3-O-ethyl Ascorbic Acid in UVA-Irradiated Human Keratinocytes.

Excessive daily exposure of human skin to natural UVA radiation leads to impaired redox homeostasis in epidermal keratinocytes, resulting in changes in their proteome. Commonly used antioxidants usually exhibit protection in a narrowed range, which makes it necessary to combine their effects. Therefore, the aim of this study was to analyze the protective effect of cannabigerol (CBG) and 3-O-ethyl ascorbic acid (EAA), used separately and together, on the proteomic profile of UVA irradiated keratinocytes. Proteomic analysis with the use of the Q Exactive HF mass spectrometer, combined with biostatistic tests, performed on UVA-irradiated keratinocytes indicated enhanced and lowered expression of 186 and 160 proteins, respectively. CBG treatment after UVA irradiation reduced these numbers to 110 upregulated and 49 downregulated proteins, while EAA eliminated all these changes. CBG completely eliminated the UV-induced effect on the expression of pro-inflammatory proteins and significantly increased the level of proteins responsible for cellular locomotion. On the other hand, CBG reduced the level of UVA-induced 4-hydroxynonenal protein adducts fivefold, whereas EAA had no effect on this modification. At the same time, CBG and EAA did not modify the expression/structure of proteins in relation to the nonirradiated control keratinocytes in the case of an unaccompanied use or slightly modified the protein profile when used in a mixture. The combined protective effects of CBG on protein structure and EAA on protein expression profile allowed us to obtain a wider protection of cells against UVA radiation, compared with when the compounds were used alone. SIGNIFICANCE STATEMENT: Proteomic analysis of human skin cells allows to conclude that 3-O-ethyl ascorbic acid eliminates UVA-induced changes in the expression of keratinocyte proteins, while cannabigerol significantly reduces 4-hydroxynonenal protein adducts. The combined protective effects of cannabigerol on protein structure and of 3-O-ethyl ascorbic acid on protein expression profile allowed to obtain a wider protection of cells against UVA radiation.