{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:13:37Z","timestamp":1789154017825,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Five Salsola species have been studied as sources of bioactive compounds using a comprehensive, untargeted metabolomic and bioactivity assessment. Plant material was extracted using ethyl acetate (EA), water, and methanol (MeOH). S. ruthenica exhibited the highest total phenolic content (46.04 mg GAE\/g, MeOH extract) and antioxidant capacity (DPPH: 47.21 mg TE\/g; ABTS: 97.40 mg TE\/g; CUPRAC: 141.38 mg TE\/g; FRAP: 80.30 mg TE\/g). Extracts of S. stenoptera and S. ruthenica showed potent cholinesterase inhibition, while S. crassa was notably active against tyrosinase. A total of 265 metabolites were annotated, revealing strong solvent- and species-specific differences in phenolic composition, as confirmed by AMOPLS analysis. Flavanols, anthocyanins, and lignans emerged as the major chemotaxonomic markers, based on PCA, contributing the most to the total variance. Strong correlations were observed between TPC and CUPRAC (r = 0.93) and between flavanols and DPPH (r = 0.70), suggesting functional relevance of these compounds in redox activity, confirming the importance of different classes of phenolic constituents. VIP markers also revealed species- and solvent-specific enrichments of metabolites. Regularized canonical correlation analysis (rCCA) further linked specific metabolites, namely Quercetin 3-O-glucosyl-xyloside and 6\u2033-O-Acetylgenistin, the flavanone sakuranetin, the lignans Secoisolariciresinol, Anhydro-secoisolariciresinol, and Medioresinol, and p-Coumaric acid ethyl ester, with antioxidant functions. These findings underscore the pharmacological potential of Salsola species and highlight the importance of valorizing metabolic diversity in the search for new sources of health-promoting natural compounds. Furthermore, the work shows the need for a tailored solvent selection in bioactivity-guided phytochemical research.<\/jats:p>","DOI":"10.3390\/plants15020199","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:56:55Z","timestamp":1767877015000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Metabolic Diversity of Different Salsola Species Valorized Through Untargeted Metabolomics and In Vitro Bioassays: The Importance of Phenolic Constituents"],"prefix":"10.3390","volume":"15","author":[{"given":"Hajar","family":"Salehi","sequence":"first","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-9048","authenticated-orcid":false,"given":"Marco Armando De","family":"Gregorio","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6548-7823","authenticated-orcid":false,"given":"Gokhan","family":"Zengin","sequence":"additional","affiliation":[{"name":"Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-3526","authenticated-orcid":false,"given":"Sakina","family":"Yagi","sequence":"additional","affiliation":[{"name":"Department of Botany, Faculty of Science, University of Khartoum, Khartoum 13314, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes","family":"Ak","sequence":"additional","affiliation":[{"name":"Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0268-7497","authenticated-orcid":false,"given":"Enver","family":"Saka","sequence":"additional","affiliation":[{"name":"Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8399-452X","authenticated-orcid":false,"given":"Fevzi","family":"Elbasan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-2027","authenticated-orcid":false,"given":"Evren","family":"Yildiztugay","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-0459","authenticated-orcid":false,"given":"Leilei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6953","authenticated-orcid":false,"given":"Stefano","family":"Dall\u2019Acqua","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5133-9464","authenticated-orcid":false,"given":"Luigi","family":"Lucini","sequence":"additional","affiliation":[{"name":"Department for Sustainable Food Process, Universit\u00e0 Cattolica del Sacro Cuore, 20123 Piacenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1080\/14756366.2022.2102005","article-title":"The old world Salsola as a source of valuable secondary metabolites endowed with diverse pharmacological activities: A review","volume":"37","author":"ElNaggar","year":"2022","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Murshid, S.S., Atoum, D., Abou-Hussein, D.R., Abdallah, H.M., Hareeri, R.H., Almukadi, H., and Edrada-Ebel, R. (2022). Genus Salsola: Chemistry, biological activities and future prospective\u2014A review. Plants, 11.","DOI":"10.3390\/plants11060714"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.38058\/ijsl.867859","article-title":"Proline accumulation in three closely related Salsola L. taxa","volume":"3","year":"2021","journal-title":"Int. J. Sci. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.sajb.2019.03.003","article-title":"Biological activities and phytochemical analysis of phenolic extracts from Salsola kali L. Role of endogenous factors in the selection of the best plant extracts","volume":"123","author":"Boulaaba","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mohammed, H.A., Al-Omar, M.S., Mohammed, S.A., Alhowail, A.H., Eldeeb, H.M., Sajid, M.S., Abd-Elmoniem, E.M., Alghulayqeh, O.A., Kandil, Y.I., and Khan, R.A. (2021). Phytochemical analysis, pharmacological and safety evaluations of halophytic plant. Salsola cyclophylla. Molecules, 26.","DOI":"10.3390\/molecules26082384"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.indcrop.2011.10.006","article-title":"Evaluation of antioxidant activities of the edible and medicinal Suaeda species and related phenolic compounds","volume":"36","author":"Oueslati","year":"2012","journal-title":"Ind. Crops Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101731","DOI":"10.1016\/j.jsps.2023.101731","article-title":"Phytochemical profiling of Salsola tetragona Delile by LC-HR\/MS and investigation of the antioxidant, anti-inflammatory, cytotoxic, antibacterial and anti-SARS-CoV-2 activities","volume":"31","author":"Cherrada","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.4103\/0973-1296.176110","article-title":"New isorhamnetin derivatives from Salsola imbricata Forssk. leaves with distinct anti-inflammatory activity","volume":"12","author":"Osman","year":"2016","journal-title":"Pharmacogn. Mag."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100942","DOI":"10.1016\/j.hermed.2024.100942","article-title":"Antimicrobial activity and molecular docking analysis of Salsola kali: Investigating potent biological interactions and chemical composition","volume":"48","author":"Aytar","year":"2024","journal-title":"J. Herb. Med."},{"key":"ref_10","first-page":"2033","article-title":"Pharmacological investigations and chemical constituents of Salsola kali aerial parts","volume":"66","author":"Abdelgawad","year":"2023","journal-title":"Egypt. J. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20221011","DOI":"10.1515\/biol-2022-1011","article-title":"Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization","volume":"19","author":"Aamer","year":"2024","journal-title":"Open Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10811-019-01927-1","article-title":"Effect of extraction method and solvent system on the phenolic content and antioxidant activity of selected macro-and microalgae extracts","volume":"32","author":"Monteiro","year":"2020","journal-title":"J. Appl. Phycol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Plaskova, A., and Mlcek, J. (2023). New insights of the application of water or ethanol-water plant extract rich in active compounds in food. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1118761"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102306","DOI":"10.1016\/j.fbio.2022.102306","article-title":"Comparative metabolomics of the different fractions of two saltwort (Salsola L.) species in relation to their anti-inflammatory activity","volume":"51","author":"Selim","year":"2023","journal-title":"Food Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1038\/s41598-024-80807-2","article-title":"A comprehensive metabolomic study of three Egyptian Salsola species revealed their potential anti-inflammatory activity","volume":"15","author":"Zakaria","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"112528","DOI":"10.1016\/j.phytochem.2020.112528","article-title":"Antioxidant action of deprotonated flavonoids: Thermodynamics of sequential proton-loss electron-transfer","volume":"180","author":"Biela","year":"2020","journal-title":"Phytochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13065-014-0048-1","article-title":"Evaluation of solvent effect on the extraction of phenolic compounds and antioxidant capacities from the berries: Application of principal component analysis","volume":"8","author":"Boeing","year":"2014","journal-title":"Chem. Cent. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Iloki-Assanga, S.B., Lewis-Luj\u00e1n, L.M., Lara-Espinoza, C.L., Gil-Salido, A.A., Fernandez-Angulo, D., Rubio-Pino, J.L., and Haines, D.D. (2015). Solvent effects on phytochemical constituent profiles and antioxidant activities, using four different extraction formulations for analysis of Bucida buceras L. and Phoradendron californicum. BMC Res. Notes, 8.","DOI":"10.1186\/s13104-015-1388-1"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e7857","DOI":"10.7717\/peerj.7857","article-title":"Solvent polarity mediates phytochemical yield and antioxidant capacity of Isatis tinctoria","volume":"7","author":"Wakeel","year":"2019","journal-title":"Peer J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27192","DOI":"10.1021\/acsomega.4c01321","article-title":"Solvent effects on the phenolic compounds and antioxidant activity associated with Camellia polyodonta flower extracts","volume":"9","author":"Xiang","year":"2024","journal-title":"ACS Omega"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"118371","DOI":"10.1016\/j.ejmech.2025.118371","article-title":"Natural alkaloids with therapeutic potential against Alzheimer\u2019s disease through cholinesterase inhibition","volume":"302","author":"Khan","year":"2026","journal-title":"Eur. J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e020724231486","DOI":"10.2174\/0115733998304373240611110224","article-title":"Molecular mechanisms underlying the therapeutic potential of plant-based \u03b1-amylase inhibitors for hyperglycemic control in diabetes","volume":"21","author":"Kaur","year":"2025","journal-title":"Curr. Diabetes Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115574","DOI":"10.1016\/j.bcp.2023.115574","article-title":"Targeting tyrosinase in hyperpigmentation: Current status, limitations and future promises","volume":"212","author":"Zolghadri","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","first-page":"300","article-title":"Radical scavenging activity and cholinesterase inhibitory activity of Leopoldia comosa (L.) bulbs","volume":"13","author":"Loizzo","year":"2011","journal-title":"Prog. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/hlca.200390045","article-title":"Three tyrosinase inhibitors and antioxidant compounds from Salsola foetida","volume":"86","author":"Khan","year":"2003","journal-title":"Helv. Chim. Acta"},{"key":"ref_26","first-page":"473","article-title":"Inhibitory effects on the digestive enzyme \u03b1-amylase of three Salsola species (Chenopodiaceae) in vitro","volume":"62","author":"Tundis","year":"2007","journal-title":"Pharmazie"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e2013344118","DOI":"10.1073\/pnas.2013344118","article-title":"Spatial and evolutionary predictability of phytochemical diversity","volume":"118","author":"Defossez","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, J.-E., Jayakody, J.T.M., Kim, J.-I., Jeong, J.-W., Choi, K.-M., Kim, T.-S., Seo, C., Azimi, I., Hyun, J., and Ryu, B. (2024). The influence of solvent choice on the extraction of bioactive compounds from Asteraceae: A comparative review. Foods, 13.","DOI":"10.3390\/foods13193151"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jchromb.2017.07.025","article-title":"Evaluation of the effect of extraction solvent and organ selection on the chemical profile of Astragalus spinosus using HPTLC-multivariate image analysis","volume":"1061","author":"Shawky","year":"2017","journal-title":"J. Chromatogr. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.phytochem.2009.05.010","article-title":"Evolution of rosmarinic acid biosynthesis","volume":"70","author":"Petersen","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mencin, M., Mikulic-Petkovsek, M., Veberi\u010d, R., and Terpinc, P. (2021). Development and optimisation of solid-phase extraction of extractable and bound phenolic acids in spelt (Triticum spelta L.) seeds. Antioxidants, 10.","DOI":"10.3390\/antiox10071085"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/aocs.12935","article-title":"Assessing the efficiency of ethyl acetate for lipid extraction as an alternative to the Folch method in selected marine low-trophic species","volume":"102","author":"Wang","year":"2025","journal-title":"J. Am. Oil Chem. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chiorcea-Paquim, A.-M. (2023). Electrochemistry of flavonoids: A comprehensive review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115667"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1021\/jf010152t","article-title":"Berry phenolics and their antioxidant activity","volume":"49","author":"Hopia","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Le Roy, J., Huss, B., Creach, A., Hawkins, S., and Neutelings, G. (2016). Glycosylation is a major regulator of phenylpropanoid availability and biological activity in plants. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.00735"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9824203","DOI":"10.1155\/2016\/9824203","article-title":"Sakuranetin inhibits inflammatory enzyme, cytokine, and costimulatory molecule expression in macrophages through modulation of JNK, p38, and STAT1","volume":"2016","author":"Kim","year":"2016","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/j.fct.2007.05.017","article-title":"Antioxidant activities of the flaxseed lignan secoisolariciresinol diglucoside, its aglycone secoisolariciresinol and the mammalian lignans enterodiol and enterolactone in vitro","volume":"45","author":"Hu","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.sjbs.2020.11.064","article-title":"Mode of action and determination of antioxidant activity in the dietary sources: An overview","volume":"28","author":"Siddeeg","year":"2021","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4314\/ajtcam.v11i2.37","article-title":"Investigation of antioxidant potentials of solvent extracts from different anatomical parts of Asphodeline anatolica E. Tuzlaci: An endemic plant to Turkey","volume":"11","author":"Zengin","year":"2014","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.phytol.2017.03.005","article-title":"In vitro enzyme inhibitory properties, antioxidant activities, and phytochemical profile of Potentilla thuringiaca","volume":"20","author":"Grochowski","year":"2017","journal-title":"Phytochem. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1002\/jsfa.13160","article-title":"The exogenous application of naringenin and rosmarinic acid modulates functional traits in Lepidium sativum","volume":"104","author":"Salehi","year":"2024","journal-title":"J. Sci. Food Agric."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"bat070","DOI":"10.1093\/database\/bat070","article-title":"Phenol-Explorer 3.0: A major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content","volume":"2013","author":"Rothwell","year":"2013","journal-title":"Database"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2047-217X-2-13","article-title":"The role of reporting standards for metabolite annotation and identification in metabolomic studies","volume":"2","author":"Salek","year":"2013","journal-title":"Gigascience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"127415","DOI":"10.1016\/j.foodchem.2020.127415","article-title":"Red beet (Beta vulgaris) and amaranth (Amaranthus sp.) microgreens: Effect of storage and in vitro gastrointestinal digestion on the untargeted metabolomic profile","volume":"332","author":"Rocchetti","year":"2020","journal-title":"Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.talanta.2018.11.019","article-title":"Removal of batch effects using stratified subsampling of metabolomic data for in vitro endocrine disruptors screening","volume":"195","author":"Boccard","year":"2019","journal-title":"Talanta"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/2\/199\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T05:29:49Z","timestamp":1768022989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/15\/2\/199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["plants15020199"],"URL":"https:\/\/doi.org\/10.3390\/plants15020199","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]}}}