chlorogenic acid; UHPLC-MS/MS; skin; anti-inflammatory; collagenase; elastase; hyaluronidase; tyrosinase http://creativecommons.org/licenses/by/4.0/legalcode 2026 Unveiling the Bioactive Potential of the Aerial Parts of Balkan Achillea clypeolata: Comparison with Officinal Achillea millefolium volume: 18 number: 5 Background/Objectives: Achillea millefolium is a well-known medicinal plant recognized in several pharmacopeias, while the Balkan endemic species Achillea clypeolata lacks a pharmacopeial monograph and remains insufficiently studied despite its traditional use. This study aimed to comparatively evaluate the phytochemical composition and biological potential of both species. Methods: Chemical composition was studied using UHPLC-MS/MS, HPLC, and FT-IR; anti-inflammatory potential was analyzed by erythrocyte membrane stabilization assay (heat- and hypotonicity-induced hemolysis); and enzyme-inhibitory activity was tested against collagenase, elastase, hyaluronidase, and tyrosinase. In addition, antioxidant activity was evaluated using DPPH, ABTS, and DCFDA assays; antimicrobial activity was determined using the broth microdilution method; and cytotoxic potential was investigated by the MTT assay. Results: The major constituents in water–ethanolic extracts were quinic acid derivatives, flavonoids, phenolic acids, and coumarins, with chlorogenic acid, 3,5-dicaffeoylquinic acid, cosmosiin, cynaroside, rutin, and hyperoside as dominant in both species. Extracts exhibited marked anti-inflammatory activity, where A. millefolium provided greater protection under heat-induced hemolysis, and both extracts showed comparable efficacy under osmotic stress. Concentration-dependent inhibition of collagenase, elastase, hyaluronidase, and tyrosinase (concentration from 62.5 to 1000 µg/mL), along with significant antioxidant activity in ABTS and DPPH assays, was observed. In MRC-5 cells, the extracts reduced AAPH-induced ROS levels up to 50 µg/mL, while higher concentrations showed diminished effects. Moderate cytotoxicity was observed, with A. clypeolata displaying stronger effects at 50–100 µg/mL. Both Achillea species exhibited broad-spectrum antimicrobial activity, with pronounced effects against Gram-positive bacteria. Conclusions: The results support the traditional use of Achillea species and highlight A. clypeolata as a promising, yet underexplored, source of bioactive compounds for dermatological and pharmaceutical applications. Šavikin, Katarina Jovanović, Aleksandra A. Pirković, Andrea Alimpić Aradski, Ana Živković, Jelena Stević, Tatjana Trendafilova, Antoaneta https://phaidrabg.bg.ac.rs/o:38886 doi:https://doi.org/10.3390/pharmaceutics18050591 info:eu-repo/semantics/article Unveiling the Bioactive Potential of the Aerial Parts of Balkan Achillea clypeolata Comparison with Officinal Achillea millefolium eng application/pdf 1745333 bytes MDPI