Multi-Target Photoprotection by Taxifolin Against UVB-Induced Keratinocyte Injury Through UVB Filtration, ROS Scavenging and Transcriptomic-Proteomic Reprogramming.

Taxifolin, a natural flavonoid, consistently exerts cytoprotective effects against various oxidative stresses. In this study, we systematically evaluated its photoprotective efficacy and underlying mechanisms against ultraviolet B (UVB)-induced injury in human immortalized keratinocytes (HaCaT). Cell viability and apoptosis were assessed by MTT, fluorescence staining, and flow cytometry, while integrative transcriptomic and proteomic analyses were employed to identify core pathways and key mediators. Taxifolin exhibited antioxidant capacity comparable to that of ascorbic acid under identical in vitro radical-scavenging assays. Moreover, it displayed a strong absorption peak at 289 nm that overlaps the UVB spectrum (280-320 nm), enabling it to act as a chemical sunscreen. In UVB-challenged HaCaT cells, taxifolin markedly reduced intracellular reactive oxygen species (ROS) and attenuated JNK/p38 MAPK activation, as evidenced by Western blot, thereby breaking the ROS-MAPK vicious cycle. Multi-omics revealed that taxifolin was associated with attenuation of UVB-imposed G1/S arrest concomitant with restored Cyclin expression, while up-regulating MYC, FOXQ1, HMOX1 and AP-1 components c-Jun/c-Fos and thereby switching on a pro-survival transcriptional program. Consequently, apoptosis was suppressed and survival was significantly improved. Collectively, taxifolin integrated chemical filtration, ROS scavenging and signaling modulation to support a multi-target photoprotective network, which provides mechanistic insight into taxifolin-mediated cytoprotection and identifies candidate molecular nodes for further validation.