Protective Effect of Auricularia polytricha Water Extract Against UVB-Induced Keratinocyte Damage by Inhibition of Ferroptosis and Apoptosis

Ultraviolet (UV) radiation causes skin damage through chronic exposure, particularly UVB, which generates reactive oxygen species (ROS) and induces oxidative stress. Although oxidative stress–related pathways in photoaging have been widely studied, the role of ferroptosis in skin aging has only recently gained attention. Auricularia polytricha (AP), commonly known as cloud ear mushroom, has demonstrated anti-aging and anti-inflammatory properties. This study investigated the protective effects of AP against UVB-induced cytotoxicity in human keratinocyte (HaCaT) cells. The cytoprotective effects of AP were demonstrated through antioxidants, apoptosis and ferroptosis detection. The underlying mechanisms mediated by UVB and AP treatment were examined using dual luciferase, western blot and untargeted metabolomic analysis. We found that UVB could induce apoptosis and ferroptosis on HaCaT cells. The water extract of AP (APW) showed the best protective effects among hexane, ethanol, and water extracts of AP against those damages. Additionally, APW at 100 μg/mL was able to suppress ROS and lipid peroxidation from UVB and recover Glutathione Peroxidase 4 (GPX4) and Ferritin heavy chain (FTH1) protein expression, suggesting an inhibition of ferroptosis. Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, a key regulator of antioxidant protection, showed activation after treatment with APW and ferrostatin-1 (Fer-1), a ferroptosis inhibitor. Moreover, APW also reduced apoptosis by inhibiting JNK and p38 signaling pathway on UVB-induced HaCaT cells. UVB-induced damages in HaCaT cells, was a response to oxidative stress imbalance, reflected by a significant reduction in the key metabolite from tryptophan metabolism like kynurenine showed markedly decreased in UVB-exposed group. The present study findings highlight the protective effects of AP by inhibiting ferroptosis and apoptosis in UVB-induced keratinocytes and warrant further investigation into its potential for mitigating UV-induced keratinocyte damage. • UVB-exposed HaCaT cells exhibited metabolomic dysregulation, in which oxidative stress triggered both apoptosis and ferroptosis. • Water extract of Auricularia polytricha could rescue HaCaT cells from UVB damage. • The JNK/p38 signaling pathway and GPX4/Nrf2 axis were inhibited by AP, contributing to the protective effects against UVB-exposed HaCaT cells.