Photoprotective Effects of Cannabidiol against Ultraviolet-B-Induced DNA Damage and Autophagy in Human Keratinocyte Cells and Mouse Skin Tissue

Abstract

Cannabidiol (CBD) has emerged as a phytocannabinoid with various beneficial effects for the skin, including anti-photoaging effects, but its mechanisms of action are not fully elucidated. The study assessed CBD’s photoprotective effects against acute ultraviolet B (UVB)-induced damage in HaCaT human keratinocyte cells and murine skin tissue. CBD (8 μM) alleviated UVB-induced cytotoxicity, apoptosis, and G2/M cell cycle arrest in HaCaT cells. The contents of γH2AX and cyclobutane pyrimidine dimers were decreased after CBD treatment. CBD reduced the production of reactive oxygen species and modulated the expression of antioxidant-related proteins such as nuclear factor erythroid 2-related factor 2 in UVB-stimulated HaCaT cells. Furthermore, CBD mitigated the UVB-induced cytotoxicity by activating autophagy. In addition, a cream containing 5% CBD showed effectiveness against UVB-induced photodamage in a murine model. The CBD cream improved the skin’s condition by lowering the photodamage scores, reducing abnormal skin proliferation, and decreasing expression of the inflammation-related protein cyclooxygenase-2 in UVB-irradiated skin tissue. These findings indicate that CBD might be beneficial in alleviating UVB-induced skin damage in humans. The photoprotective effects of CBD might be attributed to its modulatory effects on redox homeostasis and autophagy.

Restorative Effect of Microalgae Nannochloropsis oceanica Lipid Extract on Phospholipid Metabolism in Keratinocytes Exposed to UVB Radiation

“…Conversely, the PPARγ receptor plays a role in modulating inflammatory signaling by inducing the p65 subunit of the NF-κB transcription factor [ 38 ]. Consequently, the obtained results validate previous reports of increased oxidative stress and inflammatory responses in UVB-exposed keratinocytes [ 28 , 30 , 31 ].…”

“…Moreover, keratinocytes exposed to UVB radiation and then exposed to microalgae show a reduction in the level of phospholipid peroxidation products. However, considering that proteins and partly DNA can also undergo structural and functional changes under the influence of UVB radiation [31], the regenerative effect of algae can also be indicated to proteins, which was also observed in previous studies [34].…”

“…When combined with impaired antioxidant mechanisms, this results in cellular redox imbalance, leading to structural and functional modifications in essential cellular components, including proteins and membrane phospholipids [ 28 ]. Consequently, this situation promotes the release of signaling molecules that induce keratinocyte proliferation as well as trigger a pro-inflammatory response and/or ultimately leads to cell death [ 3 , 28 , 29 , 30 , 31 ]. The findings of this study align with this phenomenon, as they demonstrate a reduction in keratinocyte antioxidant capacity (assessed as TAS) under the influence of UVB radiation, subsequently altering the metabolism of membrane phospholipids, influenced by both ROS and lipolytic enzymes (PLA2, COX1/2, and LOX-5).…”

Cannabidiol-Loaded Nanostructured Lipid Carriers (NLCs) for Dermal Delivery: Enhancement of Photostability, Cell Viability, and Anti-Inflammatory Activity

“…For the CBD-NLCs, cell viabilities higher than 90% were observed for concentrations less than or equal to 12.8 µg/mL, corresponding to 11.14 μg/mL or 35.41 µM. The cytotoxicities of CBD on HaCaT and HDF cells have been reported in several studies, while the reported CBD concentrations that were not toxic to HaCaT and HDF cells were different in each study [ 2 , 47 , 48 , 49 , 50 , 51 ]. For example, the study by Sangiovanni et al indicated that CBD concentrations higher than 2.5 μM were toxic to HaCaT and HDF cells [ 47 ], whereas Petrosino et al reported that treatment of HaCaT cells with 20 μM CBD did not cause toxicity to cells [ 51 ].…”

Role of autophagy in skin photoaging: A narrative review

“…Wondrak et al [122] reported that photosensitization by both endogenous and synthetic 3-hydroxypyridine derivatives inhibited the proliferation of cultured human skin keratinocytes and fibroblasts and induced their apoptosis in a dose-dependent manner. In an independent study, Li et al [123] found that cannabinol effectively inhibited UVB-induced cytotoxicity, apoptosis, and G2/M cell cycle arrest in human keratinocytes by modulating autophagy. In addition, cannabinol counteracted aberrant cell proliferation in UVB-exposed photodamaged mouse skin and suppressed the expression of cyclooxygenase-2 protein, thereby improving the overall skin condition.…”