{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:21:26Z","timestamp":1776248486683,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Achillea clypeolata Sibth. &amp; Sm. is an endemic Balkan species traditionally used in Bulgarian folk medicine. The present study aimed to conduct untargeted metabolomic profiling and characterization of 70% methanol, 70% ethanol, and water A. clypeolata extracts via the UHPLC-ESI-Orbitrap-MS\/MS method. Furthermore, the in vitro antioxidant and antibacterial activities were determined. The putative analysis led to the identification of 62 compounds: 41 in positive and 21 in negative ionization mode. Predominant classes included flavonoids, organic acids, terpenes, fatty acids, sugars, and amino acids. The antiradical tests revealed the greatest antioxidant potential for the methanol extract, followed by the ethanol one, consistent with the findings for the total polyphenol and flavonoid contents. The antibacterial assays revealed the lowest minimum inhibitory concentration against the studied Gram-positive bacteria for the methanol extract, while the ethanol one better suppressed the Gram-negative ones\u2019 growth. Additionally, the ethanol extract had the lowest minimum bactericidal concentration (MBC) against S. aureus while the hydroalcoholic extracts\u2019s MBC was equal for the rest of the studied bacterial strains. The present findings provide additional insights into the phytochemical contents and in vitro biological activity of Achillea clypeolata, and serve as a basis for future investigations associated with its pharmacological application.<\/jats:p>","DOI":"10.3390\/foods15081367","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:15:59Z","timestamp":1776244559000},"page":"1367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["UHPLC-ESI-Orbitrap-MS\/MS Untargeted Metabolomic Profiling and In Vitro Antioxidant and Antibacterial Activity of Different Achillea clypeolata Sibth. &amp; Sm. Extracts"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-8106","authenticated-orcid":false,"given":"Mariya","family":"Choneva","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-1446","authenticated-orcid":false,"given":"Ivica","family":"Dimov","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Mollova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5205-4760","authenticated-orcid":false,"given":"Merlin","family":"Esad","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-1444","authenticated-orcid":false,"given":"Plamen","family":"Stoyanov","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"},{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-761X","authenticated-orcid":false,"given":"Rumen","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"},{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsvetelina","family":"Mladenova","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"},{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1344-624X","authenticated-orcid":false,"given":"Krasimir","family":"Todorov","sequence":"additional","affiliation":[{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"},{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2157-3858","authenticated-orcid":false,"given":"Anelia","family":"Bivolarska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, 15A Vasil Aprilov Blvd., 4002 Plovdiv, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ivanova, S., Dzhakova, Z., Gvozdeva, Y., Petkova, G., Ivanova, A., and Dzhambazova, E. (2025). The Role of Essential Oils in Sports Recovery and Performance. Molecules, 30.","DOI":"10.3390\/molecules30183771"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sajb.2023.06.048","article-title":"In vitro assessment of dermatological activity potential of Achillea clypeolata Sm. in H2O2-treated human dermal fibroblasts","volume":"160","author":"Barak","year":"2023","journal-title":"S. Afr. J. Bot."},{"key":"ref_3","first-page":"1","article-title":"The Chemical Composition of Essential Oil and Headspace Volatiles of Balkan Endemic Taxon Achillea \u00d7vandasii Velen","volume":"19","year":"2024","journal-title":"Nat. Prod. Commun."},{"key":"ref_4","first-page":"453","article-title":"Chemotaxonomic significance of the Balkan Achillea volatiles","volume":"2","author":"Radulovic","year":"2007","journal-title":"Nat. Prod. Commun."},{"key":"ref_5","first-page":"351","article-title":"Achillea kotschyi subsp. urumoffii (Hal\u00e1csy)","volume":"11","author":"Anchev","year":"2012","journal-title":"Fl. Reipubl. Popularis Bulg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17976","DOI":"10.3390\/molecules201017976","article-title":"Comparative Studies on Phenolic Composition, Antioxidant, Wound Healing and Cytotoxic Activities of Selected Achillea L. Species Growing in Turkey","volume":"20","author":"Agar","year":"2015","journal-title":"Molecules"},{"key":"ref_7","first-page":"63","article-title":"Micro-morphology of Achillea clypeolata: Contribution to the pharmacognostical profile","volume":"2","author":"Nedelcheva","year":"2012","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1080\/10412905.2005.9698991","article-title":"Aromatic Plants of Yugoslavia. III. Chemical Composition of Essential Oils of Achillea abrotanoides, A. clypeolata, A. depressa and A. stricta","volume":"17","author":"Chalchat","year":"2005","journal-title":"J. Essent. Oil Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1515\/znb-2007-0219","article-title":"Sesquiterpenes and phenolic compounds from Achillea clypeolata","volume":"62","author":"Werner","year":"2007","journal-title":"Z. Naturforsch. B"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104679","DOI":"10.1016\/j.bse.2023.104679","article-title":"Variation in the essential oil composition and in silico analysis of anti-inflammatory potential of Balkan endemic species Achillea clypeolata Sm","volume":"110","author":"Semerdijeva","year":"2023","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_11","first-page":"127","article-title":"Composition and antibacterial activity of Achillea clypeolata essential oil","volume":"20","year":"2004","journal-title":"Flavour Fragr. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.2298\/JSC200524008A","article-title":"Achillea clypeolata essential oil composition and QSRR model for predicting retention indices","volume":"86","author":"Pezo","year":"2021","journal-title":"J. Serb. Chem. Soc."},{"key":"ref_13","first-page":"48","article-title":"Antibacterial activity of methanol extract and acetone exudates from Bulgarian plants","volume":"38","author":"Sotirova","year":"2022","journal-title":"Acta Microbiol. Bulg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"755","DOI":"10.5897\/JMPR2015.5792","article-title":"Anti-acne activity of Achillea \u2018Moonshine\u2019 petroleum ether extract","volume":"9","author":"Shah","year":"2015","journal-title":"J. Med. Plants Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"A\u0107imovi\u0107, M., Zori\u0107, M., Zheljazkov, V.D., Pezo, L., \u010cabarkapa, I., Stankovi\u0107 Jeremi\u0107, J., and Cvetkovi\u0107, M. (2020). Chemical Characterization and Antibacterial Activity of Essential Oil of Medicinal Plants from Eastern Serbia. Molecules, 25.","DOI":"10.3390\/molecules25225482"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0031-9422(99)00350-7","article-title":"New sesquiterpenoids from Achillea clypeolata","volume":"52","author":"Todorova","year":"1999","journal-title":"Phytochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1016\/S0031-9422(98)00201-5","article-title":"Terpenoids from Achillea clypeolata","volume":"49","author":"Todorova","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3372\/wi.36.36105","article-title":"Multidisciplinary studies on Achillea sensu lato (Compositae\u2013Anthemideae): New data on systematics and phylogeography","volume":"36","author":"Ehrendorfer","year":"2006","journal-title":"Willdenowia"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Choneva, M., Bivolarska, A., Gyuzeleva, D., Turiyski, V., Stoyanov, P., Mladenova, T., Todorov, K., Mladenov, R., Prissadova, N., and Ardasheva, R. (2025). Putting Ethnobotany into Practice: In Vitro Antioxidant Potential and Impact on Rat Gastric Smooth Muscle Reactivity of Aqueous Extracts of Marrubium friwaldskyanum and Marrubium peregrinum. Life, 15.","DOI":"10.3390\/life15060948"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Stavrakeva, K., Metodieva, K., Benina, M., Bivolarska, A., Dimov, I., Choneva, M., Kokova, V., Alseekh, S., Ivanova, V., and Vatov, E. (2024). Metabolic Composition of Methanolic Extract of the Balkan Endemic Species Micromeria frivaldszkyana (Degen) Velen and Its Anti-Inflammatory Effect on Male Wistar Rats. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105396"},{"key":"ref_21","first-page":"7182","article-title":"Phytochemical characterization of natural leaf extracts from Achillea ligustica: HRMS analysis, antioxidant activity and brine shrimp lethality testing","volume":"27","author":"Menasri","year":"2025","journal-title":"Glob. Nest J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Raudone, L., Radu\u0161iene, J., Seyis, F., Yayla, F., Vilkickyte, G., Marksa, M., Ivanauskas, L., and C\u0131rak, C. (2022). Distribution of Phenolic Compounds and Antioxidant Activity in Plant Parts and Populations of Seven Underutilized Wild Achillea Species. Plants, 11.","DOI":"10.3390\/plants11030447"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.6001\/chemija.2025.36.2.3","article-title":"Composition of Some Macro and Micro Elements, Polyphenol Content, Antimicrobial and Antioxidant Activity of Achillea millefolium (L.) Grown in Kosovo","volume":"36","author":"Faiku","year":"2025","journal-title":"Chemija"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11686-025-01211-y","article-title":"In Vitro Antiparasitic Activity and Phytochemical Profiling of Rhaponticum repens and Achillea millefolium Methanolic Extracts Against Plasmodium falciparum and Leishmania major","volume":"71","author":"Singh","year":"2026","journal-title":"Acta Parasitol."},{"key":"ref_25","first-page":"178","article-title":"Estimation of total flavonoid content in propolis by complementary colorimetric methods","volume":"10","author":"Chang","year":"2002","journal-title":"J. Food Drug Anal."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.5344\/ajev.1965.16.3.144","article-title":"Colorimetry of total phenolics with phosphomolybdic\u2013phosphotungstic acid reagents","volume":"16","author":"Singleton","year":"1965","journal-title":"Am. J. Enol. Vitic."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: The FRAP assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1080\/10715760500210145","article-title":"Total antioxidant capacity assay of human serum using copper(II)-neocuproine as chromogenic oxidant: The CUPRAC method","volume":"39","author":"Apak","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a free radical method to evaluate antioxidant activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT Food Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"18028","DOI":"10.1038\/s41598-023-45030-5","article-title":"Efficacy of various extracting solvents on phytochemical composition and biological properties of Mentha longifolia leaf extracts","volume":"13","author":"Tourabi","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6643827","DOI":"10.1155\/2021\/6643827","article-title":"Achillea species as sources of active phytochemicals for dermatological and cosmetic applications","volume":"2021","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Berdgaleeva, A., Zhalimova, Z., Saginbazarova, A., Tulegenova, G., Zharylkassynova, D., Bazargaliyeva, A., Kuanbay, Z., Sakhanova, S., Ramazanova, A., and Bilkenova, A. (2025). Comparative phytochemical analysis and antimicrobial properties of ethanol and macerated extracts from aerial and root parts of Achillea nobilis. Molecules, 30.","DOI":"10.3390\/molecules30142957"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.jpba.2018.02.059","article-title":"A comprehensive LC\u2013MS\/MS method validation for the quantitative investigation of 37 fingerprint phytochemicals in Achillea species","volume":"154","author":"Yilmaz","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1515\/znc-2020-0149","article-title":"Phytochemical characterization of different yarrow species (Achillea sp.) and investigations into their antimicrobial activity","volume":"76","author":"Apel","year":"2020","journal-title":"Z. Naturforsch. C"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gevrenova, R., Zengin, G., Sinan, K.I., Y\u0131ld\u0131ztugay, E., Zheleva-Dimitrova, D., Picot-Allain, C., Mahomoodally, M.F., Imran, M., and Dall\u2019Acqua, S. (2021). UHPLC-MS characterization and biological insights of different solvent extracts of two Achillea species. Antioxidants, 10.","DOI":"10.3390\/antiox10081180"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Angelov, M., Ivanova, V., Stoyanov, P., Mladenov, R., Mladenova, T., Gyuzeleva, D., Zhelyazkova, S., Radoukova, T., Todorov, K., and Bogdanova, S. (2025). Metabolome and essential element analyses of five underutilized European crops reveal their nutritional properties. Metabolites, 15.","DOI":"10.3390\/metabo15110720"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11432","DOI":"10.3390\/molecules200611432","article-title":"Characterization of volatile compounds of eleven Achillea species from Turkey","volume":"20","author":"Turkmenoglu","year":"2015","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e41482","DOI":"10.1016\/j.heliyon.2024.e41482","article-title":"Spermidine-induced improvements in water relations and antioxidant defense enhance drought tolerance in yarrow (Achillea millefolium)","volume":"11","author":"Alijani","year":"2024","journal-title":"Heliyon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16070","DOI":"10.1038\/s41598-025-98887-z","article-title":"Phytochemical analysis and neuroprotective potential of Achillea santolina fractions","volume":"15","author":"Mahdy","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.3109\/13880209.2012.662235","article-title":"Investigation of optimal extraction, antioxidant and antimicrobial activities of Achillea biebersteinii and A. wilhelmsii","volume":"50","author":"Bashi","year":"2012","journal-title":"Pharm. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/ptr.2679","article-title":"Antioxidant and cytoprotective properties of infusions from leaves and inflorescences of Achillea collina","volume":"23","author":"Giorgi","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kaczorov\u00e1, D., Karalija, E., Dahija, S., Be\u0161ta-Gajevi\u0107, R., Pari\u0107, A., and \u0106avar Zeljkovi\u0107, S. (2021). Influence of extraction solvent on the phenolic profile and bioactivity of two Achillea species. Molecules, 26.","DOI":"10.3390\/molecules26061601"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e70999","DOI":"10.1002\/fsn3.70999","article-title":"Investigation of antimicrobial potential of medicinal plants against Pseudomonas aeruginosa","volume":"13","author":"Bibi","year":"2025","journal-title":"Food Sci. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15406","DOI":"10.1038\/s41598-025-00127-x","article-title":"Evaluating the efficacy of Chenopodium murale plant extract in inhibiting Streptococcus mutans and reducing dental caries risk","volume":"15","author":"Kanwal","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_45","first-page":"1063","article-title":"Essential oil composition and antibacterial activity of Achillea millefolium from different regions in northeast Iran","volume":"7","author":"Mazandrani","year":"2013","journal-title":"J. Med. Plants Res."},{"key":"ref_46","first-page":"5","article-title":"Screening of various solvents and extracts of Achillea latiloba for antibacterial and antifungal activities","volume":"60","year":"2014","journal-title":"Herba Pol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.fitote.2009.04.004","article-title":"Composition and biological activity of essential oil of Achillea ligustica naturalized in central Italy","volume":"80","author":"Maggi","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"540","DOI":"10.4103\/apjtb.apjtb_515_24","article-title":"Antioxidant, antimicrobial, and anticancer effects of Achillea filipendulina against colon cancer","volume":"14","author":"Hepokur","year":"2024","journal-title":"Asian Pac. J. Trop. Biomed."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/8\/1367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:34:00Z","timestamp":1776245640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/8\/1367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["foods15081367"],"URL":"https:\/\/doi.org\/10.3390\/foods15081367","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}