{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:16:29Z","timestamp":1790198189985,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Plataforma para a Valoriza\u00e7\u00e3o, Industrializa\u00e7\u00e3o e Inova\u00e7\u00e3o commercial para o Agroalimentar\u201d","award":["02\/C05-i01\/2022 (HIDROX (WP8| 8.3.)"],"award-info":[{"award-number":["02\/C05-i01\/2022 (HIDROX (WP8| 8.3.)"]}]},{"name":"RNEM-LVT","award":["Lisboa 2030\/FCT, LISBOA2030-FEDER-01319300"],"award-info":[{"award-number":["Lisboa 2030\/FCT, LISBOA2030-FEDER-01319300"]}]},{"name":"iNOVA4Health","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"iNOVA4Health","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Associate Laboratory LS4FUTURE","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The consumption of olive oil and olives has been steadily increasing, leading to growing interest in the sustainable management of by-products such as olive stones. This work aimed to contribute to the development of valorization strategies by studying the chemical composition and biological potential of olive stone extracts, using both conventional and eco-friendly extraction methods with various solvents. Methods: Several extracts were prepared and chemically characterized regarding their fatty acid and phenolic profiles by GC-FID and HPLC-DAD-MS\/MS, respectively. Their antioxidant, cytotoxic and antiproliferative activities were also evaluated. Results: n-Hexane Soxhlet extract yielded higher concentrations and a broader range of fatty acids when compared to the chloroform-methanol Folch extract. Oleic, palmitic, and linoleic acids were the predominant fatty acids in the extracts. A large variety of phenolic compounds were identified in extracts obtained by microwave-assisted extraction (MAE), including several flavonoids, small phenolic compounds, secoiridoids (nuezhenide and oleuropein), and hydroxytyrosol. MAE hydroalcoholic extracts showed high total phenolic content (TPC), antioxidant activity by the oxygen radical absorption capacity (ORAC) and hydroxyl radical scavenging capacity (HOSC) assays. Moreover, the aqueous ethanol (50%) and aqueous methanol (80%) extracts displayed low cytotoxicity toward the non-malignant Caco-2 cell line (IC50 values of 1.29 and 1.40 mg\/mL, respectively), while both induced complete loss of viability in the HT-29 human colon adenocarcinoma cell line at 0.63 mg\/mL. Conclusions: These findings highlight the potential of olive stone as a valuable source of bioactive compounds with antioxidant and selective antiproliferative properties. The results support their further exploration in the development of sustainable valorization strategies for olive industry by-products.<\/jats:p>","DOI":"10.3390\/ph19030447","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:45:39Z","timestamp":1773153939000},"page":"447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Valorization of Olive Stones: Chemical Composition and Bioactivity"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1002-5507","authenticated-orcid":false,"given":"Bruna","family":"Nunes","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-2966","authenticated-orcid":false,"given":"Naiara","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Quinta do Marqu\u00eas, 2780-157 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3047-0586","authenticated-orcid":false,"given":"Andreia","family":"Bento Silva","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Partid\u00e1rio","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investiga\u00e7\u00e3o Agr\u00e1ria e Veterin\u00e1ria (INIAV), I. P., Av. da Rep\u00fablica, Quinta do Marqu\u00eas, 2780-157 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-5622","authenticated-orcid":false,"given":"Joana","family":"Marto","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete M. C.","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Perfinox, Zona Industrial Lameiradas Lt 1 Mansores, 4540-423 Arouca, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1767-1797","authenticated-orcid":false,"given":"Sofia","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Sovena Portugal\u2014Consumer Goods, S.A., Rua Doutor Ant\u00f3nio Loureiro Borges 2, Edif\u00edcio Arquiparque 2 Miraflores, 1495-131 Alg\u00e9s, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8618-8299","authenticated-orcid":false,"given":"Ana Teresa","family":"Serra","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Antonio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-4634","authenticated-orcid":false,"given":"Maria Ros\u00e1rio","family":"Bronze","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Quinta do Marqu\u00eas, 2780-157 Oeiras, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Antonio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3119-8745","authenticated-orcid":false,"given":"No\u00e9lia","family":"Duarte","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-9777","authenticated-orcid":false,"given":"Ana Margarida","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Av. da Rep\u00fablica, Quinta do Marqu\u00eas, 2780-157 Oeiras, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1080\/87559129.2024.2354331","article-title":"From Olive Oil Production to By-Products: Emergent Technologies to Extract Bioactive Compounds","volume":"40","author":"Soares","year":"2024","journal-title":"Food Rev. Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xia, M., Zhong, Y., Peng, Y., and Qian, C. (2022). Olive Oil Consumption and Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1041203"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ilak Per\u0161uri\u0107, A.S., and Te\u017eak Damijani\u0107, A. (2021). Connections between Healthy Behaviour, Perception of Olive Oil Health Benefits, and Olive Oil Consumption Motives. Sustainability, 13.","DOI":"10.3390\/su13147630"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1016\/j.clnu.2022.10.001","article-title":"Effect of Olive Oil Consumption on Cardiovascular Disease, Cancer, Type 2 Diabetes, and All-Cause Mortality: A Systematic Review and Meta-Analysis","volume":"41","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1080\/10408398.2018.1438349","article-title":"Comparison of Blood Lipid-Lowering Effects of Olive Oil and Other Plant Oils: A Systematic Review and Meta-Analysis of 27 Randomized Placebo-Controlled Clinical Trials","volume":"59","author":"Ghobadi","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_6","unstructured":"International Olive Council (2025, May 09). World Market of Olive Oil and Table Olives 2024. Available online: https:\/\/www.internationaloliveoil.org\/world-market-of-olive-oil-and-table-olives-data-from-december-2024\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8728","DOI":"10.1080\/10408398.2023.2203229","article-title":"In Vivo Evidences of the Health-Promoting Properties of Bioactive Compounds Obtained from Olive By-Products and Their Use as Food Ingredient","volume":"64","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/j.1753-4887.2009.00248.x","article-title":"Olive Tree (Olea europaea) Leaves: Potential Beneficial Effects on Human Health","volume":"67","author":"El","year":"2009","journal-title":"Nutr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/1082013206070166","article-title":"Phenolic Compounds and Antioxidant Activity of Olea europaea L. Fruits and Leaves","volume":"12","author":"Silva","year":"2006","journal-title":"Food Sci. Technol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nicol\u00ec, F., Negro, C., Vergine, M., Aprile, A., Nutricati, E., Sabella, E., Miceli, A., Luvisi, A., and De Bellis, L. (2019). Evaluation of Phytochemical and Antioxidant Properties of 15 Italian Olea europaea L. Cultivar Leaves. Molecules, 24.","DOI":"10.3390\/molecules24101998"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, C., Xin, X., Zhang, J., Zhu, S., Niu, E., Zhou, Z., and Liu, D. (2022). Comparative Evaluation of the Phytochemical Profiles and Antioxidant Potentials of Olive Leaves from 32 Cultivars Grown in China. Molecules, 27.","DOI":"10.3390\/molecules27041292"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104759","DOI":"10.1016\/j.fbio.2024.104759","article-title":"Comprehensive Analysis of the Phytochemical Composition and Antitumoral Activity of an Olive Pomace Extract Obtained by Mechanical Pressing","volume":"61","author":"Ferreira","year":"2024","journal-title":"Food Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Abbattista, R., Ventura, G., Calvano, C.D., Cataldi, T.R., and Losito, I. (2021). Bioactive Compounds in Waste By-Products from Olive Oil Production: Applications and Structural Characterization by Mass Spectrometry Techniques. Foods, 10.","DOI":"10.3390\/foods10061236"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1016\/j.biortech.2007.11.027","article-title":"Olive Stone: An Attractive Source of Bioactive and Valuable Compounds","volume":"99","author":"Lama","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e70412","DOI":"10.1111\/1750-3841.70412","article-title":"Sustainable Valorization of Olive Oil By-Products: Green Extraction of Phytochemicals, Encapsulation Strategies, and Food Applications","volume":"90","author":"Laaroussi","year":"2025","journal-title":"J. Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"107495","DOI":"10.1016\/j.jfca.2025.107495","article-title":"Sustainable Valorization of Olive Stone By-Products: Opportunities and Challenges","volume":"142","author":"Elhrech","year":"2025","journal-title":"J. Food Compos. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118204","DOI":"10.1016\/j.jece.2025.118204","article-title":"From Olive Stones Waste to Valuable Resource: Exploring Various Techniques for Cellulose Extraction","volume":"13","author":"Macarez","year":"2025","journal-title":"J. Environ. Chem. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.tibtech.2015.10.008","article-title":"Exploitation of Food Industry Waste for High-Value Products","volume":"34","author":"Ravindran","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ifset.2016.04.016","article-title":"Olive By-Products for Functional and Food Applications: Challenging Opportunities to Face Environmental Constraints","volume":"35","author":"Nunes","year":"2016","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1021\/jf9806210","article-title":"Phenolic Compounds of Olive Fruit: One- and Two-Dimensional Nuclear Magnetic Resonance Characterization of N\u00fczhenide and Its Distribution in the Constitutive Parts of Fruit","volume":"47","author":"Servili","year":"1999","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"479","DOI":"10.4067\/S0718-221X2015005000043","article-title":"Characterization of Phenolic Compounds in Olive Stones of Three Moroccan Varieties","volume":"17","author":"Elbir","year":"2015","journal-title":"Maderas Cienc. Tecnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1007\/s13197-019-03904-5","article-title":"Nutritional Profile and Nutraceutical Components of Olive (Olea europaea L.) Seeds","volume":"56","author":"Maestri","year":"2019","journal-title":"J. Food Sci. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xie, P., Cecchi, L., Bellumori, M., Balli, D., Giovannelli, L., Huang, L., and Mulinacci, N. (2021). Phenolic Compounds and Triterpenes in Different Olive Tissues and Olive Oil By-Products, and Cytotoxicity on Human Colorectal Cancer Cells: The Case of Frantoio, Moraiolo and Leccino Cultivars (Olea europaea L.). Foods, 10.","DOI":"10.3390\/foods10112823"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cecchi, L., Ghizzani, G., Bellumori, M., Lammi, C., Zanoni, B., and Mulinacci, N. (2023). Virgin Olive Oil By-Product Valorization: An Insight into the Phenolic Composition of Olive Seed Extracts from Three Cultivars as Sources of Bioactive Molecules. Molecules, 28.","DOI":"10.3390\/molecules28062776"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gouvinhas, I., Garcia, J., Granato, D., and Barros, A. (2022). Seed Phytochemical Profiling of Three Olive Cultivars, Antioxidant Capacity, Enzymatic Inhibition, and Effects on Human Neuroblastoma Cells (SH-SY5Y). Molecules, 27.","DOI":"10.3390\/molecules27165057"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1021\/jf048569x","article-title":"Bioactivity and Analysis of Biophenols Recovered from Olive Mill Waste","volume":"53","author":"Obied","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/pca.631","article-title":"Recent Extraction Techniques for Natural Products: Microwave-Assisted Extraction and Pressurised Solvent Extraction","volume":"13","author":"Kaufmann","year":"2002","journal-title":"Phytochem. Anal."},{"key":"ref_29","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_30","first-page":"6614","article-title":"Microwave-Assisted Extraction of Functional Compounds from Plants: A Review","volume":"18","author":"Ocampo","year":"2023","journal-title":"BioResources"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1021\/acssuschemeng.8b06052","article-title":"Life-Cycle Assessment of Microwave-Assisted Pectin Extraction at Pilot Scale","volume":"7","author":"Rahimifard","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Catalano, T., Selvaggi, F., Cotellese, R., and Aceto, G.M. (2025). The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches. Cancers, 17.","DOI":"10.3390\/cancers17050752"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1021\/jf011506j","article-title":"Acylglycerol and Fatty Acid Components of Pulp, Seed, and Whole Olive Fruit Oils: Their Use to Characterize Fruit Variety by Chemometrics","volume":"50","author":"Ranalli","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.5209\/mbot.65609","article-title":"Amino and Fatty Acids Composition of Olive Stones for the Discrimination of Olea europaea subsp. europaea Varieties","volume":"41","author":"Hannachi","year":"2020","journal-title":"Mediterr. Bot."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Revelou, P.-K., Xagoraris, M., Alexandropoulou, A., Kanakis, C.D., Papadopoulos, G.K., Pappas, C.S., and Tarantilis, P.A. (2021). Chemometric Study of Fatty Acid Composition of Virgin Olive Oil from Four Widespread Greek Cultivars. Molecules, 26.","DOI":"10.3390\/molecules26144151"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Jimenez-Lopez, C., Carpena, M., Louren\u00e7o-Lopes, C., Gallardo-Gomez, M., Lorenzo, J.M., Barba, F.J., Prieto, M.A., and Simal-Gandara, J. (2020). Bioactive Compounds and Quality of Extra Virgin Olive Oil. Foods, 9.","DOI":"10.3390\/foods9081014"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/j.jacc.2015.07.055","article-title":"Saturated Fats Compared with Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease","volume":"66","author":"Li","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"106623","DOI":"10.1016\/j.biombioe.2022.106623","article-title":"Recovery of Oils and Antioxidants from Olive Stones","volume":"166","author":"Osei","year":"2022","journal-title":"Biomass Bioenergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1080\/14786419.2010.489048","article-title":"Optimisation and Characterisation of Various Extraction Conditions of Phenolic Compounds and Antioxidant Activity in Olive Seeds","volume":"25","author":"Alli","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"416","DOI":"10.4236\/ajac.2017.86032","article-title":"Evaluation of Standards and Interfering Compounds in the Determination of Phenolics by Folin\u2013Ciocalteu Assay Method for Effective Bioprocessing of Biomass","volume":"8","author":"Bastola","year":"2017","journal-title":"Am. J. Anal. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81112","DOI":"10.1007\/s11356-022-23337-6","article-title":"Extraction and Characterization of Phenolic Compounds and Their Potential Antioxidant Activities","volume":"29","author":"Shi","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102626","DOI":"10.1016\/j.fbio.2023.102626","article-title":"Phenolic Compounds and Contaminants in Olive Oil and Pomace\u2014A Narrative Review of Their Biological and Toxic Effects","volume":"53","author":"Schmidt","year":"2023","journal-title":"Food Biosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"682","DOI":"10.3390\/antiox4040682","article-title":"Olive Tree (Olea europaea L.) Leaves: Importance and Advances in the Analysis of Phenolic Compounds","volume":"4","author":"Abaza","year":"2015","journal-title":"Antioxidants"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1111\/1541-4337.12882","article-title":"Olive Byproducts and Their Bioactive Compounds as a Valuable Source for Food Packaging Applications","volume":"21","author":"Khwaldia","year":"2022","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Romani, A., Ieri, F., Urciuoli, S., Noce, A., Marrone, G., Nediani, C., and Bernini, R. (2019). Health Effects of Phenolic Compounds Found in Extra-Virgin Olive Oil, By-Products, and Leaf of Olea europaea L. Nutrients, 11.","DOI":"10.3390\/nu11081776"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"134808","DOI":"10.1016\/j.foodchem.2022.134808","article-title":"Fast and Selective Production of Quercetin and Saccharides from Rutin Using Microwave-Assisted Hydrothermal Treatment in the Presence of Graphene Oxide","volume":"405","author":"Sasaki","year":"2023","journal-title":"Food Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Safarzadeh Markhali, F. (2021). Effect of Processing on Phenolic Composition of Olive Oil Products and Olive Mill By-Products and Possibilities for Enhancement of Sustainable Processes. Processes, 9.","DOI":"10.3390\/pr9060953"},{"key":"ref_48","first-page":"332","article-title":"Gluc\u00f3sidos fen\u00f3licos amargos de las semillas del olivo (Olea europaea)","volume":"45","author":"Cabello","year":"1994","journal-title":"Grasas Aceites"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6716","DOI":"10.1021\/jf025736p","article-title":"Identification of Phenolic Compounds in Tissues of the Novel Olive Cultivar Hardy\u2019s Mammoth","volume":"50","author":"Ryan","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"157","DOI":"10.3989\/gya.087309","article-title":"Secoiridoids in Olive Seed: Characterization of N\u00fczhenide and 11-Methyl Oleosides by Liquid Chromatography with Diode Array and Mass Spectrometry","volume":"61","author":"Silva","year":"2010","journal-title":"Grasas Aceites"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1021\/acs.jafc.5b00353","article-title":"Phenolic Profile Characterization of Chemlali Olive Stones by Liquid Chromatography\u2013Ion Trap Mass Spectrometry","volume":"63","author":"Mansour","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1365-2621.2011.02892.x","article-title":"Evaluation of Table Olive By-Product as a Source of Natural Antioxidants","volume":"47","author":"Ros","year":"2012","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.lwt.2018.01.009","article-title":"Abscisic Acid Treated Olive Seeds as a Natural Source of Bioactive Compounds","volume":"90","author":"Flores","year":"2018","journal-title":"LWT"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Bai, L., Xu, D., Zhou, Y.-M., Zhang, Y.-B., Zhang, H., Chen, Y.-B., and Cui, Y.-L. (2022). Antioxidant Activities of Natural Polysaccharides and Their Derivatives for Biomedical and Medicinal Applications. Antioxidants, 11.","DOI":"10.3390\/antiox11122491"},{"key":"ref_55","unstructured":"Diogo, J. (2013). Valorization of Wild Olives (Olea europaea var. sylvestris) as Potential Source of Functional Ingredients, Faculdade de Ci\u00eancias da Universidade de Lisboa."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.foodchem.2016.06.001","article-title":"Phenolic Content and Antioxidant Activity of Olive By-Products and Antioxidant Film Containing Olive Leaf Extract","volume":"212","author":"Moudache","year":"2016","journal-title":"Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5590","DOI":"10.1021\/acssuschemeng.0c09426","article-title":"Pressurized Liquid Extraction Optimization from Supercritical Defatted Olive Pomace: A Green and Selective Phenolic Extraction Process","volume":"9","author":"Katsinas","year":"2021","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_58","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro Cytotoxicity (Standard No. ISO 10993-5)."},{"key":"ref_59","first-page":"071","article-title":"Phenolic compounds in grapes (genus Vitis): A review of their antioxidant activity, antiproliferative capacity, and cytotoxic effect on colorectal cancer","volume":"14","author":"Rojas","year":"2024","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fink, H., Langselius, O., Vignat, J., Rumgay, H., Rehm, J., Martinez, R.X., Santero, M., Lopez-Perez, L., Inoue, M., and Zeng, H. (2026). Global and Regional Cancer Burden Attributable to Modifiable Risk Factors to Inform Prevention. Nat. Med.","DOI":"10.1038\/s41591-026-04219-7"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-G\u00f3mez, L., and Uranga, J.A. (2024). Polyphenols in the Prevention and Treatment of Colorectal Cancer: A Systematic Review of Clinical Evidence. Nutrients, 16.","DOI":"10.3390\/nu16162735"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tan, B.L., Zulkifli, F., and Norhaizan, M.E. (2025). Dietary Polyphenols as Modulators of Cell Signaling and Inflammation in Colorectal Carcinogenesis. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1691590"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/01635581.2013.741758","article-title":"Oleuropein, a Secoiridoid Derived from Olive Tree, Inhibits the Proliferation of Human Colorectal Cancer Cells through Downregulation of HIF-1\u03b1","volume":"65","author":"Rosillo","year":"2013","journal-title":"Nutr. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Rishmawi, S., Haddad, F., Dokmak, G., and Karaman, R. (2022). A Comprehensive Review on the Anti-Cancer Effects of Oleuropein. Life, 12.","DOI":"10.3390\/life12081140"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Almatroudi, A., Alharbi, H.O.A., Khan, A.A., and Rahmani, A.H. (2024). Effects and Mechanisms of Luteolin, a Plant-Based Flavonoid, in the Prevention of Cancers via Modulation of Inflammation and Cell Signaling Molecules. Molecules, 29.","DOI":"10.3390\/molecules29051093"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Naponelli, V., Piscazzi, A., and Mangieri, D. (2025). Cellular and Molecular Mechanisms Modulated by Genistein in Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031114"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"9573","DOI":"10.1002\/jcb.27275","article-title":"The Dietary Flavone Luteolin Epigenetically Activates the Nrf2 Pathway and Blocks Cell Transformation in Human Colorectal Cancer HCT116 Cells","volume":"119","author":"Zuo","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_68","first-page":"178","article-title":"Genistein Induces Apoptosis and Inhibits Proliferation of HT29 Colon Cancer Cells","volume":"5","author":"Shafiee","year":"2016","journal-title":"Int. J. Mol. Cell Med."},{"key":"ref_69","first-page":"52","article-title":"Physico-Chemical Characteristics of Oils Extracted from Three Compartments of the Olive Fruit (Pulp, Endocarp and Seed) of Variety Chemlal Cultivated in Kabylia (Algeria)","volume":"6","author":"Moussaoui","year":"2008","journal-title":"J. Food Agric. Environ."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Alves, E., Rey, F., Melo, T., Barros, M.P., Domingues, P., and Domingues, R. (2022). Bioprospecting Bioactive Polar Lipids from Olive (Olea europaea cv. Galega vulgar) Fruit Seeds: LC\u2013HR\u2013MS\/MS Fingerprinting and Sub-Geographic Comparison. Foods, 11.","DOI":"10.3390\/foods11070951"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A Simple Method for the Isolation and Purification of Total Lipides from Animal Tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Serra, A.T., Silva, S.D., Pleno de Gouveia, L., Alexandre, A.M.R.C., Pereira, C.V., Pereira, A.B., Partid\u00e1rio, A.C., Silva, N.E., Bohn, T., and Gon\u00e7alves, V.S.S. (2021). A Single Dose of Marine Chlorella vulgaris Increases Plasma Concentrations of Lutein, \u03b2-Carotene and Zeaxanthin in Healthy Male Volunteers. Antioxidants, 10.","DOI":"10.3390\/antiox10081164"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"101505","DOI":"10.1016\/j.psj.2021.101505","article-title":"The Composition of the Lipid, Protein and Mineral Fractions of Quail Breast Meat Obtained from Wild and Farmed Specimens of Common Quail (Coturnix coturnix) and Farmed Japanese Quail (Coturnix japonica domestica)","volume":"101","author":"Quaresma","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Weng, V., Cardeira, M., Bento-Silva, A., Serra, A.T., Brazinha, C., and Bronze, M.R. (2023). Arabinoxylan from Corn Fiber Obtained through Alkaline Extraction and Membrane Purification: Relating Bioactivities with the Phenolic Compounds. Molecules, 28.","DOI":"10.3390\/molecules28155621"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.1021\/jf0201529","article-title":"High-Throughput Assay of Oxygen Radical Absorbance Capacity (ORAC) Using a Multichannel Liquid Handling System Coupled with a Microplate Fluorescence Reader in 96-Well Format","volume":"50","author":"Huang","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1021\/jf052555p","article-title":"Novel Fluorometric Assay for Hydroxyl Radical Scavenging Capacity (HOSC) Estimation","volume":"54","author":"Moore","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Oliveira-Alves, S.C., Andrade, F., Prazeres, I., Silva, A.B., Capelo, J., Duarte, B., Ca\u00e7ador, I., Coelho, J., Serra, A.T., and Bronze, M.R. (2021). Impact of Drying Processes on the Nutritional Composition, Volatile Profile, Phytochemical Content and Bioactivity of Salicornia ramosissima J. Woods. Antioxidants, 10.","DOI":"10.3390\/antiox10081312"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.mimet.2013.06.027","article-title":"Comparison of the Caco-2, HT-29 and the Mucus-Secreting HT29-MTX Intestinal Cell Models to Investigate Salmonella Adhesion and Invasion","volume":"94","author":"Gagnon","year":"2013","journal-title":"J. Microbiol. Methods"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Nollevaux, G., Devill\u00e9, C., El Moualij, B., Zorzi, W., Deloyer, P., Schneider, Y.-J., Peulen, O., and Dandrifosse, G. (2006). Development of a Serum-Free Co-Culture of Human Intestinal Epithelium Cell Lines (Caco-2\/HT29-5M21). BMC Cell Biol., 7.","DOI":"10.1186\/1471-2121-7-20"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e004142","DOI":"10.1161\/JAHA.116.004142","article-title":"Common Statistical Pitfalls in Basic Science Research","volume":"5","author":"Sullivan","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Saini, K., Prasad, P., Shang, X., and Keum, Y.-S. (2021). Advances in Lipid Extraction Methods\u2014A Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413643"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:52:02Z","timestamp":1773154322000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":81,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030447"],"URL":"https:\/\/doi.org\/10.3390\/ph19030447","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]}}}