o:38507 Bioactivities of Alchemilla alpina L. Extract on Women’s Reproductive and Metabolic Health: Antioxidant, Enzyme Inhibitory, Receptor Modulatory Properties and Potential Cytotoxic Effects en ABSTRACT Alchemilla alpina L. (Rosaceae), belongs to a genus well recognized in traditional medicine for treating gynecological disorders and hormonal imbalance; however, the specific bioactivity of A. alpina itself remains poorly characterized. This study aimed to elucidate the phenolic composition and the biological potential of the methanolic (MeOH) extract of A. alpina. LC–MS/MS analysis identified 39 phenolic compounds, with rutin, catechin, kaempferol-3-O-glucoside, and caffeic acid being the dominant constituents. The extract exhibited high total phenolic and flavonoid contents, consistent with strong antioxidant capacities. It demonstrated notable α-glucosidase and acetylcholinesterase inhibitory activities, indicating its potential relevance for metabolic and neurodegenerative disorders. The extract effectively reduced AAPH-induced ROS levels in MRC-5 fibroblasts, indicating cytoprotective and antioxidative effects. The cytotoxicity toward cervical cancer cells HeLa and ovarian cancer cells A2780 was moderate and concentration dependent. A yeast-based fluorescent screen revealed a strong and selective binding affinity toward estrogen receptor α (ERα) and selective inhibition of human recombinant AKR1C3 (59.5%), without affecting AKR1C4. Additionally, high COX-1/COX-2 inhibition (>70%) supported its anti-inflammatory potential. Collectively, these findings provide the first integrated evidence of A. alpina’s phenolic richness and multifunctional bioactivity, scientifically supporting its potential in managing hormone-dependent and oxidative stress-related disorders. Alchemilla alpina; LC-MS/MS; phenolic compounds; antioxidant activity; α-glucosidase; α-amylase; acetylcholinesterase inhibition; estrogen receptor; aldo-keto reductase; women’s reproductive health 1552099 10.3390/ijms27073025 2026-03-30T07:43:23.544Z 44 yes 46 Sanja Krstić Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria Sofija Bekić Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia person Nemanja Živanović Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia person Andrea Pirković University of Belgrade, Institute for the Application of Nuclear Energy INEP, Zemun, Belgrade, Serbia doktor bioloških nauka person 0000-0002-1182-4895 Jovana Vuković University of Belgrade, Institute for the Application of Nuclear Energy INEP, Zemun, Belgrade, Serbia person 0000-0002-6170-1826 Rudolf Bauer Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria person Milena Rašeta Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia person application/pdf 1191351 https://phaidrabg.bg.ac.rs/o:38507 no yes 16 70 92000001 11A29 11A2901 International Journal of Molecular Sciences 27 7 MDPI, Basel, Switzerland 2026