Lichen-Derived Polysaccharide from Cladina rangiferina Alleviates UVB-Induced Skin Photoaging: Potential Role of the NRF2-Mediated Antioxidant Response

In a previous study, we isolated a water-soluble heteropolysaccharide (CRWP-S) from the edible lichen Cladina rangiferina (L.) Nyl., which exhibited potent free radical-scavenging capacities. However, its protective efficacy against ultraviolet B (UVB)-induced skin photoaging and the underlying molecular mechanisms remain to be fully elucidated. In this study, we established a UVB-induced photoaging model in BALB/c mice and cell senescence model in HaCaT keratinocytes to evaluate the photoprotective effects and mechanisms of CRWP-S. Microneedle-assisted topical application of CRWP-S effectively attenuated UVB-induced macroscopic photoaging phenotypes, while mitigating dermal collagen degradation and restored NRF2 expression in vivo. CRWP-S treatment enhanced HaCaT cell viability, reduced intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Mechanistically, CRWP-S inhibited senescence-associated β-galactosidase (SA-β-Gal) activity and downregulated the expression of senescence markers p53 and p21. Furthermore, CRWP-S promoted NRF2 nuclear translocation and upregulated downstream heme oxygenase-1 (HO-1) while downregulating KEAP1 expression. Pharmacological inhibition of NRF2 using ML385 largely abolished the ROS-scavenging and cytoprotective effects of CRWP-S. Taken together, these findings demonstrate that CRWP-S protects against UVB-induced skin photoaging via activation of the KEAP1–NRF2 signaling pathway, highlighting its strong potential as a functional bioactive ingredient for anti-photoaging formulations.