UV radiation from the sun is a potent environmental risk factor in the pathogenesis of skin damage. Much of the skin damage caused by ultraviolet A (UVA) irradiation from the sun is associated with oxidative stress. The aim of this study was to investigate the protective role of ellagicacid (25–75 μM), a natural antioxidant, against UVA (5–20 J/cm2)-induced oxidative stress and apoptosis in humankeratinocyte (HaCaT) cells and to reveal the possible mechanisms underlying this protective efficacy. Ellagicacid pre-treatment markedly increased HaCaT cell viability and suppressed UVA-induced ROS generation and MDA formation. Moreover, ellagicacid pre-treatment prevented UVA-induced DNA damage as evaluated by the comet assay. Ellagicacid treatment also significantly inhibited the UVA-induced apoptosis of HaCaT cells, as measured by a reduction of DNA fragmentation, mitochondria dysfunction, ER stress, caspase-3 activation, and Bcl-2/Bax deregulation. Notably, the antioxidant potential of ellagicacid was directly correlated with the increased expression of HO-1 and SOD, which was followed by the downregulation of Keap1 and the augmented nuclear translocation and transcriptional activation of Nrf2 with or without UVA irradiation. Nrf2 knockdown diminished the protective effects of ellagicacid. Therefore, ellagicacid may be useful for the treatment of UVA-induced skin damage.
