Phytocannabinoids Regulate Lipid Metabolism in UVA-Irradiated Melanocytes.

Melanocytes are specialized skin cells that produce melanin. Under conditions of metabolic disturbances caused by UVA radiation, melanocytes may undergo neoplastic transformation, potentially leading to melanoma. This study evaluated the effects of phytocannabinoids, cannabidiol (CBD), cannabigerol (CBG), and their combination (CBD+CBG) in control cells and following UVA irradiation. Both compounds penetrated cells and localized primarily within cellular membranes. UVA exposure altered their intracellular distribution and disrupted redox homeostasis by decreasing total antioxidant status and increasing oxidative stress, as evidenced by elevated levels of lipid peroxidation products, including malondialdehyde. Administration of CBG or CBD+CBG partially prevented these changes. UVA irradiation also altered phospholipid composition and polyunsaturated fatty acids, and increased phospholipase A2 activity, which was partially counteracted by CBD and CBG. Although phytocannabinoids modulated membrane surface charge by altering sialic acid levels. Phytocannabinoids influenced fatty acid oxidation pathways mediated by cyclooxygenases. They partially reversed the UVA-induced reduction in endocannabinoids (AEA, 2-AG, PEA) and modulated eicosanoid profiles by decreasing pro-inflammatory mediators (PGE2, PGD2, 5-HETE, 12-HETE) while increasing the anti-inflammatory mediator, 15-d-PGJ2. These changes were accompanied by altered expression of membrane receptors. UVA exposure increased the expression of CB1, CB2, TRPV1, and PPARγ receptors. CBG upregulated all of these receptors, whereas CBD and CBD+CBG selectively modulated TRPV1 and PPARγ expression. In conclusion, phytocannabinoids partially restored redox balance and reduced inflammatory signaling, thereby normalizing membrane composition and cellular signaling in UVA-exposed melanocytes. These findings suggest a regulatory role for phytocannabinoids in melanocyte responses to UVA exposure, with potential implications for metabolic processes involved in neoplastic transformation.