{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:17:37Z","timestamp":1787833057087,"version":"build-2784847793"},"reference-count":38,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Council of Medical Sciences, Medical University of Sofia, Bulgaria","award":["141\/29.05.2024"],"award-info":[{"award-number":["141\/29.05.2024"]}]},{"award":["141\/29.05.2024"],"award-info":[{"award-number":["141\/29.05.2024"]}],"id":[{"id":"https:\/\/ror.org\/01n9zy652","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Helichrysum italicum is a Mediterranean medicinal plant whose phloroglucinol (PG) \u03b1-pyrones constitute a structurally distinctive and pharmacologically relevant metabolite class, yet no systematic high-resolution mass spectrometric (HRMS) study has comprehensively characterized them. In this study, the acetone extract of inflorescences from Helichrysum italicum (Roth) G. Don was profiled by UHPLC\u2013Orbitrap\u2013MS in negative ion mode using full-scan and data-dependent MS\/MS acquisition; exact-mass elemental composition assignment and HCD fragmentation analysis were combined with unsupervised clustering of fragment-ion and neutral-loss intensity matrices, validated against a manually curated annotation table using the adjusted Rand index (ARI) and cluster purity. From a total of 59 annotated compounds, 23 corresponded to known PG-\u03b1-pyrones previously reported from Helichrysum and 36 represented structures not previously described from the genus. Diagnostic fragment ions (FIs) and neutral losses (NLs) were established for identifying specific substituents of the \u03b1-pyrone and PG moieties. Semi-quantification gave a total PG-\u03b1-pyrone content of 0.019% dry weight, dominated by arzanol. This study establishes a UHPLC\u2013HRMS framework for profiling phloroglucinol \u03b1-pyrone derivatives and confirms H. italicum as a rich source of this class.<\/jats:p>","DOI":"10.3390\/plants15172619","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:58:21Z","timestamp":1787828301000},"page":"2619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive UHPLC\u2013Orbitrap\u2013MS Profiling of Phloroglucinol \u03b1-Pyrones in Helichrysum italicum (Roth) G. Don (Asteraceae)"],"prefix":"10.3390","volume":"15","author":[{"given":"Yulian","family":"Voynikov","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Pharmacy, Medical University, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodor","family":"Marinov","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5640-6120","authenticated-orcid":false,"given":"Paraskev","family":"Nedialkov","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bari\u010devi\u010d, D., Stopar, K., Bartol, T., and Luthar, Z. (2025). Genetics of Helichrysum spp. and Opportunities for Breeding. Breeding of Ornamental Crops: Annuals and Cut Flowers, Springer.","DOI":"10.1007\/978-3-031-78653-2_5"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lephatsi, M.M., Choene, M.S., Kappo, A.P., Madala, N.E., and Tugizimana, F. (2023). An integrated molecular networking and docking approach to characterize the metabolome of Helichrysum splendidum and its pharmaceutical potentials. Metabolites, 13.","DOI":"10.3390\/metabo13101104"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bojilov, D., Manolov, S., Ahmed, S., Dagnon, S., Ivanov, I., Marc, G., Oniga, S., Oniga, O., Nedialkov, P., and Mollova, S. (2023). HPLC Analysis and In Vitro and In Silico Evaluation of the Biological Activity of Polyphenolic Components Separated with Solvents of Various Polarities from Helichrysum italicum. Molecules, 28.","DOI":"10.3390\/molecules28176198"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Samanidis, I., Krigas, N., Athanasiadis, V., Makrygiannis, I., Mantiniotou, M., and Lalas, S.I. (2025). A Comparative Phytochemical Investigation of the Greek Members of the Genus Helichrysum Mill., with Emphasis on the Local Endemic Helichrysum amorginum Boiss and Orph. Plants, 14.","DOI":"10.3390\/plants14020229"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1021\/acs.jnatprod.8b01031","article-title":"HPLC-based activity profiling for antiprotozoal compounds in the endemic Iranian medicinal plant Helichrysum oocephalum","volume":"82","author":"Akaberi","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S0031-9422(00)98631-X","article-title":"Methylene-bis-2H-pyran-2-ones and phenolic constituents from the root of Helichrysum arenarium","volume":"14","year":"1975","journal-title":"Phytochemistry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0031-9422(80)85038-2","article-title":"Neue phloroglucin-derivate aus Helichrysum-arten","volume":"19","author":"Bohlmann","year":"1980","journal-title":"Phytochemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/0031-9422(80)87030-0","article-title":"Neue pyron-derivate aus Helichrysum-arten","volume":"19","author":"Cybulski","year":"1980","journal-title":"Phytochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Voynikov, Y. (2025). Phloroglucinol \u03b1-Pyrones from Helichrysum: A Review on Structural Diversity, Plant Distribution and Isolation. Plants, 14.","DOI":"10.20944\/preprints202510.1957.v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1021\/np060581r","article-title":"Arzanol, an anti-inflammatory and anti-HIV-1 phloroglucinol \u03b1-pyrone from Helichrysum italicum ssp. microphyllum","volume":"70","author":"Appendino","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1021\/np3007149","article-title":"Antimicrobial phenolics and unusual glycerides from Helichrysum italicum subsp. microphyllum","volume":"76","author":"Pollastro","year":"2013","journal-title":"J. Nat. Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.fitote.2018.12.018","article-title":"Pyrone derivatives from Helichrysum italicum","volume":"133","author":"Werner","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cbi.2006.11.006","article-title":"Evaluation of the antioxidant and cytotoxic activity of arzanol, a prenylated \u03b1-pyrone\u2013phloroglucinol etherodimer from Helichrysum italicum subsp. microphyllum","volume":"165","author":"Rosa","year":"2007","journal-title":"Chem.-Biol. Interact."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.indcrop.2017.06.043","article-title":"Everlasting flower (Helichrysum stoechas Moench) as a potential source of bioactive molecules with antiproliferative, antioxidant, antidiabetic and neuroprotective properties","volume":"108","author":"Les","year":"2017","journal-title":"Ind. Crops Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1016\/S0040-4039(01)98478-3","article-title":"Helipyron, ein methylen-bis-triacets\u00e4urelacton aus Helichrysum italicum","volume":"11","author":"Opitz","year":"1970","journal-title":"Tetrahedron Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1023\/B:CONC.0000033925.00693.7b","article-title":"Constituents of Helichrysum stoechas variety olonnense","volume":"40","author":"Lavault","year":"2004","journal-title":"Chem. Nat. Compd."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-8741(91)90160-F","article-title":"Isolation and identification of the antibacterial compounds from Helichrysum stoechas","volume":"33","author":"Rios","year":"1991","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0031-9422(00)81569-1","article-title":"Phloroglucinol derivatives and other constituents from South African Helichrysum species","volume":"25","author":"Jakupovic","year":"1986","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1016\/S0031-9422(00)97809-9","article-title":"Antifungal phloroglucinol derivatives and lipophilic flavonoids from Helichrysum decumbens","volume":"28","author":"Wray","year":"1989","journal-title":"Phytochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1002\/ejoc.201101193","article-title":"A Multicomponent Carba-Betti Strategy to Alkylidene Heterodimers\u2013Total Synthesis and Structure\u2013Activity Relationships of Arzanol","volume":"2012","author":"Minassi","year":"2012","journal-title":"Eur. J. Org. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.bcp.2010.09.025","article-title":"Arzanol, a prenylated heterodimeric phloroglucinyl pyrone, inhibits eicosanoid biosynthesis and exhibits anti-inflammatory efficacy in vivo","volume":"81","author":"Bauer","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.chemphyslip.2010.09.009","article-title":"Protective role of arzanol against lipid peroxidation in biological systems","volume":"164","author":"Rosa","year":"2011","journal-title":"Chem. Phys. Lipids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/jat.4570","article-title":"Arzanol, a natural phloroglucinol \u03b1-pyrone, protects HaCaT keratinocytes against H2O2-induced oxidative stress, counteracting cytotoxicity, reactive oxygen species generation, apoptosis, and mitochondrial depolarization","volume":"44","author":"Piras","year":"2024","journal-title":"J. Appl. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Piras, F., Sogos, V., Pollastro, F., and Rosa, A. (2024). Protective effect of arzanol against H2O2-induced oxidative stress damage in differentiated and undifferentiated SH-SY5Y Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137386"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1002\/ptr.7941","article-title":"Helichrysum stoechas (L.) Moench reduces body weight gain and modulates mood disorders via inhibition of silent information regulator 1 (SIRT1) by arzanol","volume":"37","author":"Borgonetti","year":"2023","journal-title":"Phytother. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s11030-012-9417-7","article-title":"High-throughput virtual screening of phloroglucinol derivatives against HIV-reverse transcriptase","volume":"17","author":"Belekar","year":"2013","journal-title":"Mol. Divers."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Vuji\u0107, B., Vidakovi\u0107, V., Jadranin, M., Novakovi\u0107, I., Trifunovi\u0107, S., Te\u0161evi\u0107, V., and Mandi\u0107, B. (2020). Composition, antioxidant potential, and antimicrobial activity of Helichrysum plicatum DC. various extracts. Plants, 9.","DOI":"10.3390\/plants9030337"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kramberger, K., Barli\u010d-Maganja, D., Bandelj, D., Baruca Arbeiter, A., Peeters, K., Miklav\u010di\u010d Vi\u0161njevec, A., and Jenko Pra\u017enikar, Z. (2020). HPLC-DAD-ESI-QTOF-MS determination of bioactive compounds and antioxidant activity comparison of the hydroalcoholic and water extracts from two Helichrysum italicum species. Metabolites, 10.","DOI":"10.3390\/metabo10100403"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114196","DOI":"10.1016\/j.indcrop.2021.114196","article-title":"Metabolite profiling and antiprotozoal activity of three endemic Iranian Helichrysum species","volume":"174","author":"Akaberi","year":"2021","journal-title":"Ind. Crops Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111471","DOI":"10.1016\/j.indcrop.2019.111471","article-title":"Everlasting flowers: Phytochemistry and pharmacology of the genus Helichrysum","volume":"138","author":"Akaberi","year":"2019","journal-title":"Ind. Crops Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.phytochem.2016.09.012","article-title":"Phytochemical study of Helichrysum italicum (Roth) G. Don: Spectroscopic elucidation of unusual amino-phlorogucinols and antimicrobial assessment of secondary metabolites from medium-polar extract","volume":"132","author":"Buommino","year":"2016","journal-title":"Phytochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phytochem.2017.01.001","article-title":"Separation of phytochemicals from Helichrysum italicum: An analysis of different isolation techniques and biological activity of prepared extracts","volume":"138","author":"Maksimovic","year":"2017","journal-title":"Phytochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.chemphyslip.2017.05.001","article-title":"New insights into the antioxidant activity and cytotoxicity of arzanol and effect of methylation on its biological properties","volume":"205","author":"Rosa","year":"2017","journal-title":"Chem. Phys. Lipids"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/oms.1210290908","article-title":"Fragmentation of collisionally activated hydroxyphenoxide anions in the gas phase","volume":"29","author":"Binkley","year":"1994","journal-title":"Org. Mass Spectrom."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"116397","DOI":"10.1016\/j.ijms.2020.116397","article-title":"Losses of CO and CO2 upon collision-activated dissociation of substituted 2-methoxyphenoxides after methyl radical loss","volume":"456","author":"Marcum","year":"2020","journal-title":"Int. J. Mass Spectrom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1021\/es5002105","article-title":"Identifying Small Molecules via High Resolution Mass Spectrometry: Communicating Confidence","volume":"48","author":"Schymanski","year":"2014","journal-title":"Environ. Sci. Technol."},{"key":"ref_37","unstructured":"Oksanen, J., Simpson, G.L., Blanchet, F.G., Kindt, R., Legendre, P., Minchin, P.R., O\u2019Hara, R.B., Solymos, P., Stevens, M.H.H., and Szoecs, E. (2026, July 14). vegan: Community Ecology Package, R Package Version 2.7-5. Available online: https:\/\/CRAN.R-project.org\/package=vegan."},{"key":"ref_38","first-page":"790","article-title":"Package \u2018pheatmap\u2019","volume":"1","author":"Kolde","year":"2015","journal-title":"R Package"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/17\/2619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T11:18:36Z","timestamp":1787829516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/17\/2619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["plants15172619"],"URL":"https:\/\/doi.org\/10.3390\/plants15172619","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}