Luteolin Mitigates Photoaging Caused by UVA-Induced Fibroblast Senescence by Modulating Oxidative Stress Pathways

As a polyphenolic plant flavone, luteolin (Lut) is widely found in many medicinal plants, flowers, and vegetables. Although Lut has been shown to have the effect of preventing and treating skin photoaging, its role in preventing photoaging specifically induced by ultraviolet A (UVA) radiation remains underreported. In vivo, BALB/c mice were used as models for skin photoaging models and treated with Lut. Additionally, NIH-3T3 fibroblasts were utilized in vitro to further investigate whether Lut exerts its anti-photoaging effects by enhancing fibroblast vitality and function. Several biochemical assays (CCK-8, catalase, superoxide dismutase, malondialdehyde, dichloro-dihydro-fluorescein diacetate, quantitative real-time-PCR, gene expression patterns) and histochemical (histological staining, immunofluorescent staining, SA-β-Gal experiments, western blotting analysis) were conducted. The findings demonstrate that the Lut pretreatment could enhance the vitality and function of fibroblasts in both in vitro and in vivo experiments and inhibit UVA-induced collagen degradation, thereby improving the skin's resistance to photoaging. We confirmed that the Lut pretreatment inhibited the expression of UVA-induced senescent factors P21, P16, and pro-inflammatory senescence-associated secretory phenotype (SASP) factors. Additionally, Lut exhibited potent antioxidant effects during UVA exposure. Bioinformatics and network pharmacology analyses revealed that Lut's anti-photoaging effects may be mediated through the regulation of oxidative stress-related pathways and anti-aging genes. Upon utilizing inhibitors and agonists of oxidative stress, we further confirmed that Lut prevents UVA-induced fibroblast senescence by suppressing oxidative stress, and ultimately protects the skin from photoaging damage. These findings indicate that lutein mitigates photoaging caused by UVA-induced fibroblast senescence through the modulation of oxidative stress pathways.