418 Protection against AhR-induced oxidative stress and premature skin aging

Abstract

Pollution is a major concern in our urbanized and industrialized countries. As a result, the skin is in contact with particulate matter (PM), which are tiny pollution particles associated to polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HM). Deleterious effects of these pollutants on the skin are now well described. Key players induced by pollutants following activation of Aryl hydrocarbon receptor (AhR) are the noxious Reactive Oxygen Species (ROS). We showed in keratinocytes that AhR was activated following application of calibrated HM or PAHs and in the mean time we measured an increase of ROS production. A more close-to-reality model, ex vivo skin explant, was then exposed to a mix of HM and PAHs to check for pollutants damaging effects. After HM/PAHs treatment, we measured an increase of malonaldehyde (MDA), a lipid peroxidation product. This oxidative stress causes dramatic biological consequences occurring during skin aging: a deterioration of dermo-epidermal junction (DEJ), an overexpression of MMP-1 protein, and a decrease of collagen type I expression. AhR activation regulates the expression of the NADPH oxidases (NOX) that are major contributors of ROS production. Intracellular ROS activate AP-1 signalling which in turn stimulates inflammatory pathways evidenced here by COX2 and MMP1 expression. Camellia Japonica flower extract exhibits an interesting antioxidant activity measured by DPPH assay (radical scavenging), thus constituting a good candidate for skin protection from harmful pollutants. We showed in keratinocytes, that this extract limits AhR activation and abrogates HM and PAHs dependent ROS induction. In addition, we showed in ex vivo model that this extract limits NOX related inflammatory pathways activation by inhibiting MMP1 and COX2 induction but stimulates collagen type I expression and preserves the global tissue morphology. Moreover, clinical results confirmed this anti-aging effect. In conclusion, we propose Camellia japonica flower extract as a powerful active ingredient fighting against pollutants-induced premature skin aging.