Abstract
Pistacia lentiscus L. is widely reported in the ethnobotanical literature for its use in treating various pathologies, particularly skin disorders such as burns, inflammation, and wounds. These traditional applications suggest broader potential anti-aging activity and support the exploration of simple and sustainable extraction strategies. In this study, an aqueous extract obtained from leaf hydrodistillation residues, representing a by-product of essential oil production, was chemically characterized by LC-ESI-QToF-MS/MS and HPLC-PDA. The analysis identified 32 compounds, including 8 gallic acid derivatives, accounting for 70.7% of the total extract, and 24 flavonol glycosides. High total phenolic and flavonoid contents were associated with strong antioxidant activity, confirmed by the ABTS assay and by a dose-dependent intracellular ROS reduction in keratinocytes. The extract exhibited significant inhibitory activities against key skin-aging-related enzymes, with IC(50) of 33.8 µg/mL and 17.4 µg/mL, respectively for tyrosinase and elastase. Notably, strong anti-hyaluronidase activity, IC(50) 4.3 µg/mL, is reported here for the first time, while no collagenase inhibition was observed. The cytotoxicity assay demonstrated a favorable safety profile at biologically active concentrations. Overall, these results highlight the bioactivity of the P. lentiscus phenolic phytocomplex and support the valorization of hydrodistillation aqueous residues as a sustainable source of multifunctional bioactive compounds for dermocosmetic applications.