Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes

Abstract

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 ellagic acid (25-75 μM), a natural antioxidant, against UVA (5-20 J/cm(2))-induced oxidative stress and apoptosis in human keratinocyte (HaCaT) cells and to reveal the possible mechanisms underlying this protective efficacy. Ellagic acid pre-treatment markedly increased HaCaT cell viability and suppressed UVA-induced ROS generation and MDA formation. Moreover, ellagic acid pre-treatment prevented UVA-induced DNA damage as evaluated by the comet assay. Ellagic acid 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 ellagic acid 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 ellagic acid. Therefore, ellagic acid may be useful for the treatment of UVA-induced skin damage.