Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid of Cannabis sativa L., is one of the most studied compounds in pharmacotherapeutic approaches to treat oxidative stress-related diseases such as cardiovascular, metabolic, neurodegenerative, and neoplastic diseases. The literature data to date indicate the possibility of both antioxidant and pro-oxidative effects of CBD. Thus, the mechanism of action of this natural compound in the regulation of nuclear factor 2 associated with erythroid 2 (Nrf2), which plays the role of the main cytoprotective regulator of redox balance and inflammation under oxidative stress conditions, seems to be particularly important. Moreover, Nrf2 is strongly correlated with the cellular neoplastic profile and malignancy, which in turn is critical in determining the cellular response induced by CBD under pathophysiological conditions. This paper summarizes the CBD-mediated pathways of regulation of the Nrf2 system by altering the expression and modification of both proteins directly involved in Nrf2 transcriptional activity and proteins involved in the relationship between Nrf2 and the nuclear factor kappa B (NF-κB) which is another redox-sensitive transcription factor.

Keratinocytes, the major cell type of the epidermis, are particularly sensitive to environmental factors including exposure to sunlight and chemical agents. Since oxidative stress may arise as a result of these factors, compounds are actively sought that can act as protective agents. Recently, cannabidiol (CBD), a phytocannabinoid found in Cannabis Sativa L., has gained increased interest due to its anti-inflammatory and antioxidant properties, and absence of psychoactive effects. This prompted us to analyze the protective effects of CBD on keratinocytes exposed to UVB irradiation and hydrogen peroxide. Here we show, using liquid chromatography mass spectrometry, that CBD was able to penetrate keratinocytes, and accumulated within the cellular membrane. CBD reduced redox balance shift, towards oxidative stress, caused by exposure UVB/hydrogen peroxide, estimated by superoxide anion radical generation and total antioxidant status and consequently lipid peroxidation level. CBD was found to protect keratinocytes by preventing changes in the composition of the cellular membrane, associated with UVB/hydrogen peroxide damages which included reduced polyunsaturated fatty acid levels, increased sialic acid and lipid peroxidation products (malondialdehyde and 8-isoprostanes) levels. This maintains cell membranes integrity and prevents the release of lactate dehydrogenase. In addition, CBD prevented UVB/hydrogen peroxide-induced reduction of keratinocyte size and zeta potential, and also decreased activity of ATP-binding cassette membrane transporters. Together, these findings suggest that CBD could be a potential protective agent for keratinocytes against the harmful effects of irradiation and chemical environmental factors that cause oxidative stress.

Cannabidiol (CBD), as the only phytocannabinoid that has no psychoactive effect, has both antioxidant and anti-inflammatory effects, and thus might be suggested as a cytoprotective compound against UV-induced metabolic changes in skin cells. Therefore, the aim of this study was to investigate the level of protective CBD activity by evaluating the proteomic profile of 2D and 3D cultured skin fibroblasts models following exposure to UVA and UVB radiation. The CBD cytoprotective effect against UV-induced damage in 2D and 3D cultured fibroblasts were different. The main alterations focus on the range of cell reaction and involved different proteins associated with various molecular functions. In the 2D cultured cells, following UV radiation, the major changes were associated with proteins involved in antioxidant response and inflammation, while, in the 3D cultured fibroblasts, CBD action against UV induced changes were mainly associated with the activation of signalling pathways. Therefore, the knowledge of the CBD action in a multilayer skin cells model allowed for the prediction of changes in cell-cell interactions and skin cell metabolism. Knowledge about the lower protective effect of CBD in 3D cultured fibroblasts should be taken into account during the design of UV light protection.

UV phototherapy used in chronic skin diseases causes redox imbalance and pro-inflammatory reactions, especially in the case of unchanged skin cells. To prevent the harmful effects of UV radiation, cannabidiol (CBD) has been used, which has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effect of CBD on the metabolism of skin keratinocytes in nude rats exposed to UVA/UVB radiation using a proteomic approach. The results obtained with SDS-PAGE/nanoHPLC/QexactiveOrbiTrap show that exposure of rat's skin to UVA/UVB radiation, as well as the action of CBD, significantly modified the expression of proteins involved in inflammation, redox balance and apoptosis. UVA/UVB radiation significantly increased the expression and biological effectiveness of the nuclear factor associated with erythroid factor 2 (Nrf2) and cytoprotective proteins being products of its transcriptional activity, including superoxide dismutase (Cu,Zn-SOD) and the inflammatory response (nuclear receptor coactivator-3 and paralemmin-3), while CBD treatment counteracted and partially eliminated these changes. Moreover, cannabidiol reversed changes in the UV-induced apoptotic pathways by modifying anti-apoptotic and pro-apoptotic factors (apoptosis regulator Bcl-2 and transforming growth factor-beta). The results show that CBD maintains keratinocyte proteostasis and therefore could be suggested as a protective measure in the prevention of UV-induced metabolic changes in epidermal keratinocytes. (C) 2020 The Author(s). Published by Elsevier B.V.

Ultraviolet (UV) radiation contained in sunlight disturbs the redox state of skin cells, leading to changes in the structures and functions of macromolecules including components of biological membranes. Cannabidiol (CBD), which accumulates in biomembranes, may be a promising protective antioxidant compound. Accordingly, the aim of this study was to compare the effects of short-term (24 h) and long-term (48 h) CBD application on the proteomic profile of biological membranes in UVB-irradiated keratinocytes. The data obtained show that UVB radiation quantitatively and qualitatively modified cell membrane proteins, with a particular research focus on adducts of proteins with the lipid peroxidation products malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE). CBD application reduced the UVB-enhanced level of these protein adducts. This was particularly notable amongst proteins related to cell proliferation and apoptosis. Moreover, CBD dramatically increased the UVB-induced expression of proteins involved in the regulation of protein translation and cell proliferation (S3a/L13a/L7a ribosomal proteins), the inflammatory response (S100/S100-A6 proteins), and maintenance of redox balance (peroxiredoxin-1, carbonyl reductase 1, and aldo-keto reductase family 1 members). In contrast, CBD effects on the level of 4-HNE-protein adducts involved in the antioxidant response and proteasomal degradation process indicate that CBD may protect keratinocytes in connection with protein catabolism processes or pro-apoptotic action.