Enhancing Photoprotection and Mitigating Ex Vivo Stratum Corneum Oxidative Stress: A Multifunctional Strategy Combining Rosmarinic Acid with UVB Filters

Exposure to ultraviolet (UV) radiation is a major contributor to skin injury, including sunburn, photoaging, and augmented risk of skin cancer, primarily through the generation of reactive oxygen species (ROS) that induce oxidative stress. Rosmarinic acid (RA), a natural phenolic compound with antioxidant and several other biological properties, has shown promise in mitigating such damage when incorporated into sunscreens. We evaluated RA's possible interactions and potential to enhance the efficacy of three worldwide known UVB filters-ethylhexyl methoxycinnamate (EHMC), octocrylene (OCT), and ethylhexyl salicylate (EHS). The performance of sunscreens with and without RA (0.1% w/w) was analyzed through in vitro and in vivo photoprotective assessments. The HPLC-TBARS-EVSC (high-performance liquid chromatography-thiobarbituric acid reactive substances-ex vivo stratum corneum) protocol, which quantified oxidative stress reduction in the human stratum corneum, was also used. The in vitro photoprotective assays showed that RA had distinct levels of interactions with the UVB filters. When associated with EHMC, RA exclusively acted in the UVB range (SPF-enhancing effect). Remarkably, for EHS, RA contributed to a higher efficacy profile in the total UV spectrum. OCT-RA was the sample that reached the highest critical wavelength value parallelly to OCT, boosting the in vivo SPF by more than 157% in comparison to OCT. However, its in vitro SPF performance was not affected by the RA addition, being comparable to OCT, EHS, and EHS-RA. Furthermore, the HPLC-TBARS-EVSC protocol highlighted RA's ability to reduce lipid peroxidation, with OCT-RA exhibiting the most notable protective effect. These findings underscore RA's potential as a multifunctional additive in sunscreen systems, enhancing both photoprotection and oxidative stress mitigation.