Comparative Phytochemical and Biological Evaluation of Four Thymus Species From Türkiye for Dermocosmetic Applications.

Species of Thymus have long been used in Anatolia for wound healing and skin disorders. This study characterized metabolites and biological activities of four taxa-Thymus leucostomus (TL), Thymus sipyleus (TS), Thymus brachychilus (TB), and Thymus migricus (TM)-using UHPLC-HRMS/MS-based molecular networking, anti-aging enzyme inhibition assays, and cellular models (L929 fibroblasts, HaCaT keratinocytes, HUVEC endothelial cells). All taxa showed triterpene-rich profiles, though TL was enriched in polymethoxylated flavonoids and TM in diterpenes. Extracts strongly inhibited hyaluronidase, collagenase and elastase, with more modest tyrosinase inhibition; the highest values were recorded for TB (hyaluronidase, 89.64%), TM (elastase, 78.31%), and TL (collagenase, 82.92%; tyrosinase, 39.74%). Biologically, TL demonstrated the broadest cytocompatibility and significantly enhanced wound closure in fibroblast (≈84.7%) and keratinocyte (≈71.3%) models. TL and TS achieved nearly complete endothelial wound closure, suggesting potential pro-regenerative effects. TL showed lower cytotoxicity in HaCaT and HUVEC cells (IC50 ≈ 0.5 mg/mL), whereas TM exhibited stronger cytotoxicity in keratinocytes (IC50 ≈ 0.1025 mg/mL). TM moderately increased intracellular ROS levels in L929 fibroblasts, while TL and TS maintained ROS levels closer to control conditions. Overall, TL and TS displayed more balanced in vitro profiles regarding wound closure, oxidative balance, and enzyme inhibition, whereas TM required more cautious concentration-dependent interpretation.