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‐isoPGF 2 α . 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 NF κ B and TNF α . By counteracting oxidative stress and changes in lipid structure in keratinocytes, CBD prevents cellular metabolic disturbances, protecting the epidermis against UV damage.
Psoriasis, one of the most frequent immune-mediated skin diseases, is manifested by numerous psoriatic lessons on the skin caused by excessive proliferation and keratinization of epidermal cells. These disorders of keratinocyte metabolism are caused by a pathological interaction with the cells of the immune system, including lymphocytes, which in psoriasis are also responsible for systemic inflammation. This is accompanied by oxidative stress, which promotes the formation of lipid peroxidation products, including reactive aldehydes and isoprostanes, which are additional pro-inflammatory signaling molecules. Therefore, the presented review is focused on highlighting changes that occur during psoriasis development at the level of lipid peroxidation products, including 4-hydroxynonenal, 4-oxononenal, malondialdehyde, and acrolein, and their influence on protein structures. Furthermore, we will examine inducing agents of cellular functioning, as well as intercellular signaling. These lipid peroxidation products can form adducts with a variety of proteins with different functions in the body, including proteins within skin cells and cells of the immune system. This is especially true in autoimmune diseases such as psoriasis. For example, these changes concern proteins involved in maintaining redox homeostasis or pro-inflammatory signaling. Therefore, the formation of such adducts should attract attention, especially during the design of preventive cosmetics or anti-psoriasis therapies.
Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years.
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