The skin covers the outer surface of the body, so the epidermal keratinocytes within it are susceptible to reactive oxygen species (ROS) generated by environmental pollutants such as benzo(a)pyrene (BaP), a potent activator of aryl hydrocarbon receptor (AHR). Antioxidant activity is generally mediated by the nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase-1 (HO1) axis in human keratinocytes. Perillaldehyde is the main component of Perilla frutescens, which is a medicinal antioxidant herb traditionally consumed in East Asia. However, the effect of perillaldehyde on the AHR/ROS and/or NRF2/HO1 pathways remains unknown. In human keratinocytes, we found that perillaldehyde (1) inhibited BaP-induced AHR activation and ROS production, (2) inhibited BaP/AHR-mediated release of the CCL2 chemokine, and (3) activated the NRF2/HO1 antioxidant pathway. Perillaldehyde is thus potentially useful for managing inflammatory skin diseases or disorders related to oxidative stress.
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