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Ultraviolet (UV) radiation is a main environmental factor responsible for skin damage, leading to oxidative stress, inflammation, and impairment of the skin barrier function. Furthermore, many components in sunscreen may accumulate in aquatic systems, causing environmental pollution. Therefore, the identification of novel natural bioactives that counteract these effects and can be useful as effective adjuvants in sunscreen formulations is of particular interest. Morin (1), a natural flavonoid, represents an attractive scaffold for modifications to enhance its biological activity. Herein, we aimed to investigate the effects of combining the flavonoid 1 and its derivative, morin semicarbazone (2), with the carotenoid fucoxanthin (FX) on UVB-exposed HaCaT keratinocytes. All compounds exhibited higher radical scavenging activity compared to Trolox. In this cell model, the phenolic–carotenoid combinations provided greater photoprotection than individual compounds, significantly enhancing cell viability and reducing necrosis, FX-2 emerged as the most potent combination, as evidenced by a marked reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, likely mediated through the activation of the nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, the tested treatments exerted enhanced anti-inflammatory effects by significantly reducing interleukin-6 (IL-6), cyclooxygenase 2 (COX-2), and matrix metalloproteinase-9 (MMP-9) mediators, with FX-2 being the most active combination. In conclusion, our findings highlight the protective effects of the combinations of these phenolics with the carotenoid FX against UVB radiation and support their potential application as natural active ingredients in sunscreen formulations. Full article

Ultraviolet (UV) radiation harms the skin, causing oxidative damage, inflammation, and disruption of the skin’s barrier function. There is considerable interest in identifying new natural ingredients with antioxidant and anti-inflammatory properties to serve as adjuvants in sunscreens. The flavonoid morin (1) can undergo structural modifications to enhance its biological properties. The aim of this study was to synthesize two new morin-Schiff base derivatives, morin oxime (2) and morin semicarbazone (3), comparing their photoprotective effects with that of the parent compound on UVB-exposed HaCaT keratinocytes. The chemical structure of the novel compounds was revealed based on spectroscopic data analysis. Our findings demonstrated that derivatives 2 and 3 enhanced the light absorption capability in the UV–visible (vis) range compared to 1. Tested compounds exhibited a higher scavenger capacity than Trolox. Moreover, pre-treatment with all compounds protected HaCaT cells from UVB-induced cell death. Compound 3 demonstrated the strongest antioxidant effect, reducing reactive oxygen species (ROS) generation and, subsequently, malondialdehyde (MDA) levels. Additionally, compounds 2 and 3 exhibited greater anti-inflammatory effects than compound 1, significantly reducing interleukin (IL)-6 production levels at all tested concentrations. These findings have demonstrated, for the first time, a promising photoprotective activity of two new Schiff base derivatives and suggest their use as natural sunscreen ingredients. Full article