{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:27:31Z","timestamp":1793348851237,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIMA Project"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>This study investigates the effects of extraction technique, solvent type, and geographical origin on the recovery of bioactive compounds from Arbutus unedo L. leaves collected from two Croatian islands (Vis and Mali Lo\u0161inj) and extracted using conventional, Soxhlet, and ultrasound-assisted extraction (UAE) with green solvents (distilled water, 70% ethanol, and ethyl acetate). Extracts were purified and characterized by thin-layer chromatography, column chromatography, and FTIR spectroscopy. Total phenols, hydroxycinnamic acids, flavonols, condensed tannins, and antioxidant capacity were quantified spectrophotometrically. Solvent type had the greatest influence, with 70% ethanol yielding the highest levels of bioactives and antioxidant capacity. Geographical origin significantly affected total phenolics and condensed tannins, with leaves from Vis outperforming those from Mali Lo\u0161inj. UAE was slightly more efficient than conventional and Soxhlet methods, particularly for thermolabile phenolics. Machine learning algorithms were applied as exploratory tools, using total phenols as a proxy variable to estimate selected bioactive compounds and antioxidant capacity based on extraction parameters. Decision Tree and Gradient Boosting models showed high goodness of fit within the experimental dataset (R2 &gt; 0.91). These results support the potential of green extraction strategies combined with data-driven screening for the valorization of A. unedo leaf extracts, while highlighting the need for further validation prior to industrial application.<\/jats:p>","DOI":"10.3390\/foods15060993","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:43:27Z","timestamp":1773225807000},"page":"993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Predicting Bioactive Compounds in Arbutus unedo L. Leaves Using Machine Learning: Influence of Extraction Technique, Solvent Type, and Geographical Location"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-7536","authenticated-orcid":false,"given":"Jasmina","family":"Lapi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3014-1675","authenticated-orcid":false,"given":"Anica","family":"Bebek Markovinovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolina","family":"Ra\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana","family":"Vujani\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-994X","authenticated-orcid":false,"given":"Marko","family":"Kosti\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, University of Novi Sad, Trg Dositeja Obradovi\u0107a 8, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161an","family":"Raki\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology, University of Novi Sad, Blvd. Cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senka","family":"Djakovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6829-6472","authenticated-orcid":false,"given":"Danijela","family":"Bursa\u0107 Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2478\/fhort-2018-0014","article-title":"Diversity in phenolic compounds, biochemical and pomological characteristics of Arbutus unedo fruits","volume":"30","author":"Ercisli","year":"2018","journal-title":"Folia Hortic."},{"key":"ref_2","first-page":"1794621","article-title":"An Insight into Phytochemical, Pharmacological, and Nutritional Properties of Arbutus unedo L. from Morocco","volume":"2021","author":"Assem","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jep.2018.07.004","article-title":"Arbutus unedo L.: From traditional medicine to potential uses in modern pharmacotherapy","volume":"225","author":"Morgado","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s42535-024-01090-0","article-title":"Influence of environmental factors on phenolic compounds and antioxidant activity in natural populations of the strawberry tree (Arbutus unedo) in Morocco","volume":"38","author":"Oussif","year":"2024","journal-title":"Vegetos"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1007\/s00468-021-02137-4","article-title":"Seasonal variation of phenolic compounds in Strawberry tree (Arbutus unedo L.) leaves and inhibitory potential on Phytophthora cinnamomi","volume":"35","author":"Martins","year":"2021","journal-title":"Trees"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"\u0160ic \u017dlabur, J., Bogdanovi\u0107, S., Vo\u0107a, S., and Skendrovi\u0107 Babojeli\u0107, M. (2020). Biological Potential of Fruit and Leaves of Strawberry Tree (Arbutus unedo L.) from Croatia. Molecules, 25.","DOI":"10.3390\/molecules25215102"},{"key":"ref_7","first-page":"101297","article-title":"Impact of altitudinal variation on secondary metabolites, antioxidant, anti-inflammatory and anticancer potential of Adiantum venustum D. Don","volume":"18","author":"Kimta","year":"2024","journal-title":"J. Agric. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131918","DOI":"10.1016\/j.foodchem.2021.131918","article-title":"Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products","volume":"378","author":"Romero","year":"2022","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13020-018-0177-x","article-title":"Techniques for extraction and isolation of natural products: A comprehensive review","volume":"13","author":"Zhang","year":"2018","journal-title":"Chin. Med."},{"key":"ref_10","first-page":"e01585","article-title":"A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants","volume":"19","author":"Bitwell","year":"2023","journal-title":"Sci. Afr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1007\/s11694-022-01697-4","article-title":"A comparison of conventional and novel phytonutrient extraction techniques from various sources and their potential applications","volume":"17","author":"Khongthaw","year":"2022","journal-title":"J. Food Meas. Charact."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ultsonch.2016.06.035","article-title":"Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review","volume":"34","author":"Chemat","year":"2017","journal-title":"Ultrason. Sonochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Piroddi, L. (2022). Machine Learning for Scientific Data Analysis. Special Topics in Information Technology, Springer. SpringerBriefs in Applied Sciences and Technology.","DOI":"10.1007\/978-3-030-85918-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/s41598-023-49839-y","article-title":"Optimization of ultrasound-aided extraction of bioactive ingredients from Vitis vinifera seeds using RSM and ANFIS modeling with machine learning algorithm","volume":"14","author":"Kunjiappan","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Mantiniotou, M., Athanasiadis, V., Liakos, K.G., Bozinou, E., and Lalas, S.I. (2025). Artificial Intelligence and Extraction of Bioactive Compounds: The Case of Rosemary and Pressurized Liquid Extraction. Processes, 13.","DOI":"10.3390\/pr13061879"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.crfs.2021.03.011","article-title":"Extraction of phenolic compounds: A review","volume":"4","author":"Alara","year":"2021","journal-title":"Curr. Res. Food Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.foodchem.2015.05.099","article-title":"Effects of cold atmospheric gas phase plasma on anthocyanins and color in pomegranate juice","volume":"190","author":"Putnik","year":"2016","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ifset.2018.03.009","article-title":"High pressure processing (HPP) of aronia berry pur\u00e9e: Effects on physicochemical properties, microbial counts, bioactive compounds, and antioxidant capacities","volume":"47","author":"Yuan","year":"2018","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1002\/jsfa.1532","article-title":"Antioxidant capacity and phenolic content in blueberries as affected by genotype and growing season","volume":"83","author":"Howard","year":"2003","journal-title":"J. Sci. Food Agric."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1021\/jf980366j","article-title":"Critical Factors of Vanillin Assay for Catechins and Proanthocyanidins","volume":"46","author":"Sun","year":"1998","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4337","DOI":"10.1007\/s13197-018-3383-8","article-title":"UPLC\u2013DAD quantification of chemical constituents of Potentilla atrosanguinea roots and their antioxidant activity","volume":"55","author":"Walia","year":"2018","journal-title":"J. Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, Q., Zhang, Y., Xie, M., Zhao, Z., Yang, L., Liu, J., and Hou, D. (2023). Estimation of Fv\/Fm in Spring Wheat Using UAV-Based Multispectral and RGB Imagery with Multiple Machine Learning Methods. Agronomy, 13.","DOI":"10.3390\/agronomy13041003"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461770","DOI":"10.1016\/j.chroma.2020.461770","article-title":"Selective extraction of bioactive compounds from plants using recent extraction techniques: A review","volume":"1635","author":"Lefebvre","year":"2021","journal-title":"J. Chromatogr. A"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.seppur.2007.03.006","article-title":"Optimization of ethanol\u2013water extraction of lignans from flaxseed","volume":"57","author":"Zhang","year":"2007","journal-title":"Sep. Purif. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.tifs.2021.11.019","article-title":"Extraction of bioactive compounds from plant materials using combination of various novel methods: A review","volume":"119","author":"Jha","year":"2022","journal-title":"Trends Food Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"137841","DOI":"10.1016\/j.foodchem.2023.137841","article-title":"Trends in extracting Agro-byproducts\u2019 phenolics using non-thermal technologies and their combinative effect: Mechanisms, potentials, drawbacks, and safety evaluation","volume":"437","author":"Boateng","year":"2023","journal-title":"Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1007\/s13197-020-04433-2","article-title":"Recent advances and comparisons of conventional and alternative extraction techniques of phenolic compounds","volume":"57","year":"2020","journal-title":"J. Food Sci. Technol."},{"key":"ref_29","first-page":"385473","article-title":"Quantitative Determination of Flavonoids and Chlorogenic Acid in the Leaves of Arbutus unedo L. Using Thin Layer Chromatography","volume":"2013","year":"2013","journal-title":"J. Anal. Methods Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.foodchem.2015.08.095","article-title":"Assessment of the differences in the physical, chemical and phytochemical properties of four strawberry cultivars using principal component analysis","volume":"194","author":"Duralija","year":"2016","journal-title":"Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/BBJ\/2016\/26488","article-title":"Determination of Phenolic Contents, Antioxidant and Antibacterial Activities of Strawberry Tree (Arbutus unedo L.) Leaf Extracts","volume":"14","author":"Bouyahya","year":"2016","journal-title":"Br. Biotechnol. J."},{"key":"ref_32","first-page":"192","article-title":"Phenolic Composition and Antioxidant Activity of Leaves of Strawberry Tree (Arbutus unedo L.) Populations from Morocco","volume":"20","author":"Zetlaoui","year":"2021","journal-title":"Phytoth\u00e9rapie"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Qaderi, M.M., Martel, A.B., and Strugnell, C.A. (2023). Environmental Factors Regulate Plant Secondary Metabolites. Plants, 12.","DOI":"10.3390\/plants12030447"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.3390\/nu2121231","article-title":"Chemistry and Biochemistry of Dietary Polyphenols","volume":"2","author":"Tsao","year":"2010","journal-title":"Nutrients"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhong, R., Wei, J., Liu, B., Luo, H., Zhang, Z., Pang, X., and Fang, F. (2022). Metabolite and Transcriptome Profiles of Proanthocyanidin Biosynthesis in the Development of Litchi Fruit. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010532"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bebek Markovinovi\u0107, A., Milo\u0161evi\u0107, S., Tesli\u0107, N., Pavli\u0107, B., Putnik, P., Br\u010di\u0107 Kara\u010donji, I., Jurica, K., Lasi\u0107, D., and Bursa\u0107 Kova\u010devi\u0107, D. (2023). Development of a Pressurized Green Liquid Extraction Procedure to Recover Antioxidant Bioactive Compounds from Strawberry Tree Fruit (Arbutus unedo L.). Plants, 12.","DOI":"10.3390\/plants12102006"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28591","DOI":"10.1038\/srep28591","article-title":"Influence of Environmental Factors on the Active Substance Production and Antioxidant Activity in Potentilla fruticosa L. and Its Quality Assessment","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, L., Wen, K.-S., Ruan, X., Zhao, Y.-X., Wei, F., and Wang, Q. (2018). Response of Plant Secondary Metabolites to Environmental Factors. Molecules, 23.","DOI":"10.3390\/molecules23040762"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1080\/15538362.2020.1741058","article-title":"Growing Location Affects Physical Properties, Bioactive Compounds, and Antioxidant Activity of Pomegranate Fruit (Punica granatum L. var. Gabsi)","volume":"20","author":"Boussaa","year":"2020","journal-title":"Int. J. Fruit Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Radu\u0161ien\u0117, J., Karpavi\u010dien\u0117, B., Raudone, L., Vilkickyte, G., \u00c7\u0131rak, C., Seyis, F., Yayla, F., Marksa, M., Rimkien\u0117, L., and Ivanauskas, L. (2023). Trends in Phenolic Profiles of Achillea millefolium from Different Geographical Gradients. Plants, 12.","DOI":"10.3390\/plants12040746"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Urbonaviciene, D., Bobinaite, R., Viskelis, P., Bobinas, C., Petruskevicius, A., Klavins, L., and Viskelis, J. (2022). Geographic Variability of Biologically Active Compounds, Antioxidant Activity and Physico-Chemical Properties in Wild Bilberries (Vaccinium myrtillus L.). Antioxidants, 11.","DOI":"10.3390\/antiox11030588"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1080\/10826068.2020.1728696","article-title":"An overview of cell disruption methods for intracellular biomolecules recovery","volume":"50","author":"Gomes","year":"2020","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lohvina, H., S\u00e1ndor, M., and Wink, M. (2021). Effect of Ethanol Solvents on Total Phenolic Content and Antioxidant Properties of Seed Extracts of Fenugreek (Trigonella foenum-graecum L.) Varieties and Determination of Phenolic Composition by HPLC-ESI-MS. Diversity, 14.","DOI":"10.3390\/d14010007"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1039\/D1GC03662A","article-title":"Sustainability of green solvents\u2014Review and perspective","volume":"24","author":"Hessel","year":"2022","journal-title":"Green Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Antony, A., and Farid, M. (2022). Effect of Temperatures on Polyphenols during Extraction. Appl. Sci., 12.","DOI":"10.3390\/app12042107"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"116732","DOI":"10.1016\/j.trac.2022.116732","article-title":"Green solvents and approaches recently applied for extraction of natural bioactive compounds","volume":"157","author":"Hashemi","year":"2022","journal-title":"TrAC Trends Anal. Chem."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/6\/993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:28:03Z","timestamp":1773379683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/15\/6\/993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["foods15060993"],"URL":"https:\/\/doi.org\/10.3390\/foods15060993","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]}}}