Protective Effects of Syringaresinol against UVB-Induced Human Dermal Fibroblast Senescence and Apoptosis
DOI:
https://doi.org/10.48048/tis.2025.9395Keywords:
Syringaresinol, UVB, Human dermal fibroblasts, Antioxidant system, Cellular senescence, Apoptosis, PhotoagingAbstract
UV radiation can cause skin photoaging by damaging DNA and generating excess intracellular ROS in skin cells. This study aimed to evaluate the protective effects of syringaresinol (Syr) isolated from Carallia brachiata on UVB-induced skin cell damage. Syr demonstrated potent antioxidant activity, IC50 16.90 ± 0.89 μM, by DPPH assay. To evaluate the protective effect of Syr, human dermal fibroblasts, BJ cells, were pretreated with Syr, at noncytotoxic concentrations (3 - 30 μM), for 24 h before UVB irradiation. Syr increased cell survival and the levels of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO-1) of the irradiated cells. It also increased the level of nuclear Nrf-2, an important transcription factor for antioxidant gene expression. Syr suppressed UVB-induced ROS production. It attenuated UVB-induced cellular senescence by decreasing the number of β-galactosidase (β-gal) positive cells, suppressing p21, and reducing senescence-associated secretory phenotype (SASP) including levels of pro-inflammatory cytokines and matrix metalloproteinases (MMP1, MMP3), and increasing the level of collagen-1A1 (COL-1A1). Syr prevented UVB-induced DNA damage by decreasing cyclobutane pyrimidine dimer (CPD) photoproducts. Syr also suppressed UVB-induced apoptosis of BJ cells by decreasing the levels of active caspase 3, cleaved poly (ADP-ribose) polymerase (PARP). Syr remarkably inhibited the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) proteins of the mitogen-activated protein kinase (MAPK) signaling pathway. It also inhibited the activation of nuclear factor kappa B (NF-κB). The results in this study suggest that Syr prevents UVB-induced dermal fibroblast damage, possibly via its antioxidant activity through down-regulating MAPK signaling and NF-κB activation. The protective effects of Syr lead to suppression of ROS production, DNA damage, senescence, and apoptosis of the UVB-irradiated cells.
HIGHLIGHTS
- Low-dose UVB irradiation causes aging of human dermal fibroblasts by increasing intracellular ROS, DNA damage and senescence biomarkers.
- High-dose UVB irradiation triggers apoptosis of human dermal fibroblasts.
- Syringaresinol protects dermal fibroblasts from UVB-induced damage through its antioxidant activity by downregulating MAPK signaling and inhibiting NF-κB activation.
- Syringaresinol has protective effects on UVB-irradiated human skin fibroblasts by reducing ROS production, preventing DNA damage, mitigating senescence and apoptosis, and restoring Type I collagen production.
GRAPHICAL ABSTRACT
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