Syringaresinol prevents human epidermal keratinocytes from oxidative stress, DNA damage, and cellular senescence induced by UVB irradiation

Context: UV radiation is a major external factor that harms the skin, causing photoaging and cancer through DNA damage and oxidative stress. This leads to cellular senescence and photoaging. Syringaresinol (Syr), a potential antioxidant, has a high possibility of taking part in the prevention of these detrimental effects from UV exposure. Aims: To evaluate the protective effects of an antioxidant, Syr, on oxidative stress, DNA damage, and cellular senescence induced by UVB radiation in human epidermal keratinocytes (HEKs). Methods: HEKs were treated with Syr at 3, 10, and 30 µM for 24 hours before UVB irradiation at 40 mJ/cm². The protective effects of Syr on irradiated cells were assessed by measuring intracellular ROS levels with the DCFDA assay and identifying senescent cells with the SA-β-gal assay. Western blot analysis was conducted to determine antioxidant enzymes, senescence markers MMPs and p21, transcription factors NF-κB and Nrf2, and MAPKs. ELISA was used to measure pro-inflammatory cytokine levels and cyclobutane pyrimidine dimer (CPD) photoproducts. Results: Syr significantly reduced UVB-induced oxidative stress by decreasing intracellular ROS levels and enhancing the cellular antioxidant system, including Nrf2 and related enzymes. Syr also reduced UVB-induced DNA damage by lowering CPD photoproduct levels. Furthermore, Syr prevented cellular senescence by reducing the number of senescent cells and levels of senescence-associated secretory phenotype products, including pro-inflammatory cytokines (TNF-α, IL-1, IL-6), MMP-1, MMP-3, and p21. Additionally, Syr modulated key signaling molecules involved in UV-induced photoaging by decreasing phosphorylated MAPKs (p38, pERK, pJNK) and nuclear NF-κB levels. Conclusions: Syringaresinol demonstrated protective effects against UVB-induced oxidative stress, DNA damage, and cellular senescence in HEKs, suggesting its potential as an antiphotoaging agent.