Antioxidant and Anti-inflammatory Effect of Cannabidiol Contributes to the Decreased Lipid Peroxidation of Keratinocytes of Rat Skin Exposed to UV Radiation

Abstract
There is a great need for compounds with antioxidant and anti-inflammatory properties for protection against UV radiation, which is the most prooxidative physical factor that skin cells are exposed to everyday. Therefore, the aim of the study was to evaluate the mechanism of phytocannabinoid-cannabidiol (CBD) action in vivo on lipid metabolism in keratinocytes of rat skin exposed to UVA/UVB radiation. Our results show that CBD protects keratinocytes against the effects of UVA/UVB radiation by reducing lipid peroxidation products: 4-HNE and 8-isoPGF2α. In addition, CBD significantly increases the level of endocannabinoids, such as anandamide, 2-arachidonylglycerol, and palmitoylethanolamide, and the activation of their receptors CB1/2 or TRPV1. The above changes are due to the protective effect of CBD against the UVA/UVB-induced decrease in the level/activity of superoxide dismutase and the components of the thioredoxin and glutathione systems. CBD also increases the in vivo transcriptional activity of Nrf2 and the expression of its Bach1 inhibitor as well as preventing the UVA/UVB-induced increase in the expression of Nrf2 activators p21, p62, p38, and KAP1 and proinflammatory factors such as NFκB and TNFα. By counteracting oxidative stress and changes in lipid structure in keratinocytes, CBD prevents cellular metabolic disturbances, protecting the epidermis against UV damage.