{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:24:01Z","timestamp":1778127841792,"version":"3.51.4"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Berry fruits are rich in nutrients and polyphenols, providing potential health benefits. Understanding the factors that affect their bioavailability is becoming of utmost importance for evaluating their biological significance and efficacy as functional food. In this study, the phytochemical composition and the total antioxidant capacity of different varieties of five berries (blackberry, blackcurrant, blueberry, raspberry, and strawberry) were evaluated after an in vitro gastrointestinal digestion process. The cultivar of each berry that showed the higher content of total phenols and flavonoids was selected to study its cytotoxic effect on human hepatoma cells. Digestion resulted in a high reduction (p \u02c2 0.05) of total phenolic, flavonoid and anthocyanin contents and total antioxidant capacity, in the \u201cIN\u201d samples compared to the \u201cOUT\u201d extracts, which represent the \u201cserum-available\u201d and the \u201ccolon-available\u201d fractions, respectively. Incubation of the digested fraction for 24 h didn\u2019t exert any effect on cellular viability, while a dose- and time-dependent cytotoxicity was observed after 48 h and 72 h of incubation for all the berries analyzed. Our results suggest that the approach proposed in this work may represent a rapid tool for evaluating and identifying new berries with increased phytochemical bioavailability, highlighting their antiproliferative agents after an in vitro digestion.<\/jats:p>","DOI":"10.3390\/molecules23081918","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T11:22:34Z","timestamp":1533122554000},"page":"1918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Phytochemical Composition and Cytotoxic Effects on Liver Hepatocellular Carcinoma Cells of Different Berries Following a Simulated In Vitro Gastrointestinal Digestion"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-9132","authenticated-orcid":false,"given":"Francesca","family":"Giampieri","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5063-9900","authenticated-orcid":false,"given":"Sadia","family":"Afrin","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-4265","authenticated-orcid":false,"given":"Derek","family":"Stewart","sequence":"additional","affiliation":[{"name":"The James Hutton Institute, Dundee DD2 5DA, UK"},{"name":"Department of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK"},{"name":"Division of Food Production and Society, Norwegian Institute of Bioeconomy Research, Pb 115, NO-1431 \u00c5s, Norway"}]},{"given":"Gordon J.","family":"McDougall","sequence":"additional","affiliation":[{"name":"The James Hutton Institute, Dundee DD2 5DA, UK"}]},{"given":"Rex","family":"Brennan","sequence":"additional","affiliation":[{"name":"The James Hutton Institute, Dundee DD2 5DA, UK"}]},{"given":"Lesley","family":"Blyth","sequence":"additional","affiliation":[{"name":"The James Hutton Institute, Dundee DD2 5DA, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-2663","authenticated-orcid":false,"given":"Massimiliano","family":"Gasparrini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]},{"given":"Luca","family":"Mazzoni","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Universit\u00e0 Politecnica delle Marche, Via Ranieri 65, 60131 Ancona, Italy"}]},{"given":"Franco","family":"Capocasa","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Universit\u00e0 Politecnica delle Marche, Via Ranieri 65, 60131 Ancona, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-1498","authenticated-orcid":false,"given":"Jos\u00e8 Miguel","family":"Alvarez-Suarez","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda y Ciencias Agropecuarias (FICA), Grupo de Investigaci\u00f3n en Biotecnolog\u00eda Aplicada a Biomedicina (BIOMED), Universidad de Las Am\u00e9ricas, Jos\u00e9 Queri y Ave. de los Granados, Quito 170513, Ecuador"}]},{"given":"Stefano","family":"Bompadre","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze Biomediche e Sanita\u2019 Pubblica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]},{"given":"Pedro","family":"Nogueira Br\u00e1s de Oliveira","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Investigacao Agraria e Veterinaria (INIAV), 2780-113 Carcavelos, Portugal"}]},{"given":"Claudia","family":"N. Santos","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2781-901 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7555-5017","authenticated-orcid":false,"given":"Manuel","family":"Masias","sequence":"additional","affiliation":[{"name":"Center for Nutrition &amp; Health. CITICAN, Universidad Europea del Atl\u00e1ntico, Parque Cient\u00edfico y Tecnol\u00f3gico de Cantabria C\/Isabel Torres 21, 39011 Santander, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9436-2082","authenticated-orcid":false,"given":"Pablo","family":"Agudo","sequence":"additional","affiliation":[{"name":"Center for Nutrition &amp; Health. CITICAN, Universidad Europea del Atl\u00e1ntico, Parque Cient\u00edfico y Tecnol\u00f3gico de Cantabria C\/Isabel Torres 21, 39011 Santander, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7589-5337","authenticated-orcid":false,"given":"Jorge","family":"Crespo","sequence":"additional","affiliation":[{"name":"Center for Nutrition &amp; Health. CITICAN, Universidad Europea del Atl\u00e1ntico, Parque Cient\u00edfico y Tecnol\u00f3gico de Cantabria C\/Isabel Torres 21, 39011 Santander, Spain"}]},{"given":"Bruno","family":"Mezzetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Agrarie, Alimentari e Ambientali, Universit\u00e0 Politecnica delle Marche, Via Ranieri 65, 60131 Ancona, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-9276","authenticated-orcid":false,"given":"Tamara Y.","family":"Forbes-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-1782","authenticated-orcid":false,"given":"Maurizio","family":"Battino","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche-Sez. Biochimica, Facolt\u00e0 di Medicina, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1017\/S1368980011002515","article-title":"Mediterranean diet foundation expert group. Mediterranean diet pyramid today. Science and cultural updates","volume":"14","author":"Berry","year":"2011","journal-title":"Public Health Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brglez Mojzer, E., Knez Hrn\u010di\u010d, M., \u0160kerget, M., Knez, \u017d., and Bren, U. (2016). Polyphenols: Extraction methods, antioxidative action, bioavailability and anticarcinogenic effects. Molecules, 21.","DOI":"10.3390\/molecules21070901"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/ajcn\/78.1.57","article-title":"Intake of fruit and vegetables and the risk of ischaemic stroke in a cohort of Danish men and woman","volume":"78","author":"Johnsen","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fct.2017.01.018","article-title":"Anti-inflammatory effect of strawberry extract against LPS-induced stress in RAW 264.7 macrophages","volume":"102","author":"Gasparrini","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11130-010-0177-1","article-title":"Berries: Improving human health and healthy aging, and promoting quality life\u2014A review","volume":"65","year":"2010","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.nut.2011.08.009","article-title":"The strawberry: Composition, nutritional quality, and impact on human health","volume":"28","author":"Giampieri","year":"2012","journal-title":"Nutrition"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3233\/JBR-160140","article-title":"Nutraceutical properties of wild berry fruits from Southern Italy","volume":"6","author":"Caruso","year":"2016","journal-title":"J. Berry Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3233\/JBR-160127","article-title":"Multi-radical (ORACMR5) antioxidant capacity of selected berries and effects of food processing","volume":"6","author":"Prior","year":"2016","journal-title":"J. Berry Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.foodchem.2008.02.039","article-title":"Chemistry, natural sources, dietary intake and pharmacokinetic properties of ferulic acid: A review","volume":"109","author":"Zhao","year":"2008","journal-title":"Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s11101-007-9077-x","article-title":"Bioavailability of phenolic compounds","volume":"7","author":"Lafay","year":"2008","journal-title":"Phytochem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.fct.2013.03.023","article-title":"Antioxidant and anticancer activities of Chenopodium quinoa leaves extracts\u2014In vitro study","volume":"57","author":"Swieca","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"230S","DOI":"10.1093\/ajcn\/81.1.230S","article-title":"Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies","volume":"81","author":"Manach","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Teng, Z., Yuan, C., Zhang, F., Huan, M., Cao, W., Li, K., Yang, J., Cao, D., Zhou, S., and Mei, Q. (2012). Intestinal absorption and first-pass metabolism of polyphenol compounds in rat and their transport dynamics in Caco-2 cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029647"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1080\/10715760000301341","article-title":"The gastrointestinal tract: A major site of antioxidant action?","volume":"33","author":"Halliwell","year":"2000","journal-title":"Free Radic. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jff.2014.07.019","article-title":"Antioxidant activity induced by main polyphenols present in edible artichoke heads: Influence of in vitro gastro-intestinal digestion","volume":"10","author":"Garbetta","year":"2014","journal-title":"J. Funct. Foods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.foodchem.2010.08.036","article-title":"In vitro human digestion models for food applications","volume":"125","author":"Hur","year":"2011","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.foodchem.2008.04.068","article-title":"Combining quality and antioxidant attributes in the strawberry: The role of the genotype","volume":"111","author":"Capocasa","year":"2008","journal-title":"Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1021\/jf0719959","article-title":"Antioxidants, phenolic compounds, and nutritional quality of different strawberry genotypes","volume":"56","author":"Tulipani","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jfca.2012.07.007","article-title":"Standardized method for evaluation of strawberry (Fragaria \u00d7 ananassa Duch.) germplasm collections as a genetic resource for fruit nutritional compounds","volume":"28","author":"Diamanti","year":"2012","journal-title":"J. Food. Compos. Anal."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/14786419.2012.706294","article-title":"The potential impact of strawberry on human health","volume":"27","author":"Giampieri","year":"2012","journal-title":"Nat. Prod. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jfca.2015.05.006","article-title":"Physico-chemical characteristics of thermally processed pure\u00b4e from different strawberry genotypes","volume":"43","author":"Diamanti","year":"2015","journal-title":"J. Food Compos. Anal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30917","DOI":"10.1038\/srep30917","article-title":"Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells","volume":"8","author":"Amatori","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"205","article-title":"The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans","volume":"43","author":"Parra","year":"2004","journal-title":"Eur. J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1021\/jf050131p","article-title":"Assessing potential bioavailability of raspberry anthocyanins using an in vitro digestion system","volume":"53","author":"McDougall","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.foodchem.2014.05.135","article-title":"Stability and biological activity of wild blueberry (Vaccinium angustifolium) polyphenols during simulated in vitro gastrointestinal digestion","volume":"165","author":"McDonald","year":"2014","journal-title":"Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.foodchem.2014.12.009","article-title":"Antioxidant and antiproliferative activity of chokeberry juice phenolics during in vitro simulated digestion in the presence of food matrix","volume":"175","author":"Mojsin","year":"2015","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.foodres.2014.08.049","article-title":"Bioavailability of cranberry bean hydroalcoholic extract and its inhibitory effect against starch hydrolysis following in vitro gastrointestinal digestion","volume":"64","author":"Chiang","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1016\/j.phytochem.2005.09.003","article-title":"Anthocyanins from red wine\u2014Their stability under simulated gastrointestinal digestion","volume":"66","author":"McDougall","year":"2005","journal-title":"Phytochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1155\/2016\/3297363","article-title":"Wild raspberry subjected to simulated gastrointestinal digestion improves the protective capacity against ethyl carbamate-induced oxidative damage in Caco-2 Cells","volume":"2016","author":"Chen","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.foodchem.2011.10.025","article-title":"Neuroprotective effect of blackberry (Rubus sp.) polyphenols is potentiated after simulated gastrointestinal digestion","volume":"131","author":"Tavares","year":"2012","journal-title":"Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.tibtech.2012.08.001","article-title":"Relevance and challenges in modeling human gastric and small intestinal digestion","volume":"30","author":"Guerra","year":"2012","journal-title":"Trends Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3945\/jn.109.120584","article-title":"In vitro starch digestion kinetic, corrected for estimated gastric emptying, predict portal glucose appearance in pigs","volume":"140","author":"Regmi","year":"2010","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1080\/10408398.2015.1051919","article-title":"The healthy effects of strawberry polyphenols: Which strategy behind antioxidant capacity?","volume":"56","author":"Gasparrini","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1021\/jf405455n","article-title":"Strawberry and human health: Effects beyond antioxidant activity","volume":"62","author":"Giampieri","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1002\/mnfr.201300822","article-title":"Urinary metabolite profiling identifies novel colonic metabolites and conjugates of phenolics in healthy volunteers","volume":"58","author":"Dew","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chen, S., Wei, C., Gong, H., Li, L., and Ye, X. (2016). Chemical and cellular assays combined with in vitro digestion to determine the antioxidant activity of flavonoids from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167484"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15538362.2016.1219292","article-title":"Romina and Cristina: Two new strawberry cultivars with high sensorial and nutritional values","volume":"16","author":"Capocasa","year":"2016","journal-title":"Int. J. Fruit Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5344\/ajev.1977.28.1.49","article-title":"Total phenol analysis: Automation and comparison with manual methods","volume":"28","author":"Slinkard","year":"1977","journal-title":"Am. J. Enol. Vitic."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1021\/jf0115589","article-title":"Thermal processing enhances the nutritional values of tomatoes by increasing the total antioxidant activity","volume":"50","author":"Dewanto","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Giusti, M.M., and Wrolstad, R.E. (2001). Characterization and measurement of anthocyanins by UV-Visible spectroscopy. Current Protocols in Food Analytical Chemistry, John Wiley & Sons Inc.","DOI":"10.1002\/0471142913.faf0102s00"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1002\/1097-0010(200007)80:9<1307::AID-JSFA638>3.0.CO;2-P","article-title":"Antioxidant properties of domesticated and wild Rubus species","volume":"80","author":"Deighton","year":"2000","journal-title":"J. Sci. Food Agric."},{"key":"ref_44","unstructured":"Maines, M.D., Costa, L.G., Reed, D.J., Sassa, S., and Sipes, I.G. (1998). Current Protocols in Toxicology, John Wiley & Sons."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/1918\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:15:48Z","timestamp":1760195748000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/8\/1918"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,1]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["molecules23081918"],"URL":"https:\/\/doi.org\/10.3390\/molecules23081918","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,1]]}}}