Protective Effects of Xanthorrhizol-Rich Extracts Against PM-Induced Skin Damage in Human Keratinocytes and 3D-Reconstructed Skin Models.

Particulate matter (PM) is a major environmental pollutant that induces oxidative stress, inflammation, and extracellular matrix (ECM) degradation, leading to skin damage and accelerated aging. Xanthorrhizol (XAN), a bioactive compound derived from Roxb., exhibits anti-inflammatory and antioxidative properties, making it a promising candidate for protecting against PM-induced skin damage. This study investigated the protective effects of XAN and supercritical extract (CXSE) on PM-exposed skin cells. A 3D-reconstructed skin model and HaCaT human keratinocytes were exposed to PM (100 µg/mL) with or without CXSE or XAN. Histological analysis, enzyme-linked immunosorbent assay (ELISA), Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and reporter gene assays were performed to assess the ECM integrity, inflammatory cytokine production, aryl hydrocarbon receptor (AhR) activation, and oxidative stress responses. PM exposure activates AhR and mitogen-activated protein kinases (MAPK) signaling, increases reactive oxygen species (ROS) levels, and upregulates matrix metalloproteinases (MMPs) and inflammatory cytokines. CXSE and XAN suppresses AhR-mediated transcriptional activity and downregulates the expression of AhR target genes. Additionally, CXSE and XAN reduces ROS production by upregulating antioxidant enzyme-related genes. CXSE and XAN protect against PM-induced skin damage by inhibiting oxidative stress, inflammation, and ECM degradation, highlighting their potential as natural anti-pollution skincare ingredients.