{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:46:27Z","timestamp":1789137987103,"version":"build-2803163510"},"reference-count":92,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T00:00:00Z","timestamp":1638576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEES-CONARE","award":["115-B2-657 and ED-3239"],"award-info":[{"award-number":["115-B2-657 and ED-3239"]}]},{"DOI":"10.13039\/501100005298","name":"University of Costa Rica","doi-asserted-by":"publisher","award":["115-B0-047 and ED-2033"],"award-info":[{"award-number":["115-B0-047 and ED-2033"]}],"id":[{"id":"10.13039\/501100005298","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is increasing interest in research into fruits as sources of secondary metabolites because of their potential bioactivities. In this study, the phenolic profiles of Malus domestica Anna and Jonagold cultivars from Costa Rica were determined by Ultra Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry (HRMS) using a quadrupole-time-of-flight analyzer (UPLC-QTOF-ESI MS), on enriched-phenolic extracts from skins and flesh, obtained through Pressurized Liquid Extraction (PLE). In total, 48 different phenolic compounds were identified in the skin and flesh extracts, comprising 17 flavan-3-ols, 12 flavonoids, 4 chalcones, 1 glycosylated isoprenoid and 14 hydroxycinnamic acids and derivatives. Among extracts, the flesh of Jonagold exhibits a larger number of polyphenols and is especially rich in procyanidin trimers, tetramers and pentamers. Evaluating total phenolic content (TPC) and antioxidant activities using ORAC and DPPH procedures yields higher values for this extract (608.8 mg GAE\/g extract; 14.80 mmol TE\/g extract and IC50 = 3.96 \u00b5g\/mL, respectively). In addition, cytotoxicity evaluated against SW620 colon cancer cell lines and AGS gastric cancer cell lines also delivered better effects for Jonagold flesh (IC50 = 62.4 and 60.0 \u00b5g\/mL, respectively). In addition, a significant negative correlation (p &lt; 0.05) was found between TPC and cytotoxicity values against SW620 and AGS adenocarcinoma (r = \u22120.908, and \u22120.902, respectively). Furthermore, a significant negative correlation (p &lt; 0.05) was also found between the number of procyanidins and both antioxidant activities and cytotoxicity towards SW620 (r = \u22120.978) and AGS (r = \u22120.894) cell lines. These results align with Jonagold flesh exhibiting the highest abundance in procyanidin oligomers and yielding better cytotoxic and antioxidant results. In sum, our findings suggest the need for further studies on these Costa Rican apple extracts\u2014and particularly on the extracts from Jonagold flesh\u2014to increase the knowledge on their potential benefits for health.<\/jats:p>","DOI":"10.3390\/molecules26237367","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T03:10:38Z","timestamp":1638760238000},"page":"7367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["HRMS Characterization, Antioxidant and Cytotoxic Activities of Polyphenols in Malus domestica Cultivars from Costa Rica"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-4677","authenticated-orcid":false,"given":"Mirtha","family":"Navarro-Hoyos","sequence":"first","affiliation":[{"name":"Bioactivity & Sustainable Development (BIODESS) Group, Department of Chemistry, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-4429","authenticated-orcid":false,"given":"Elizabeth","family":"Arn\u00e1ez-Serrano","sequence":"additional","affiliation":[{"name":"Department of Biology, Costa Rica Institute of Technology (TEC), Cartago 7050, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-5378","authenticated-orcid":false,"given":"Silvia","family":"Quesada-Mora","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-9207","authenticated-orcid":false,"given":"Gabriela","family":"Azofeifa-Cordero","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-1626","authenticated-orcid":false,"given":"Krissia","family":"Wilhelm-Romero","sequence":"additional","affiliation":[{"name":"Bioactivity & Sustainable Development (BIODESS) Group, Department of Chemistry, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1377-6935","authenticated-orcid":false,"given":"Maria Isabel","family":"Quir\u00f3s-Fallas","sequence":"additional","affiliation":[{"name":"Bioactivity & Sustainable Development (BIODESS) Group, Department of Chemistry, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-2189","authenticated-orcid":false,"given":"Diego","family":"Alvarado-Corella","sequence":"additional","affiliation":[{"name":"Bioactivity & Sustainable Development (BIODESS) Group, Department of Chemistry, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-0403","authenticated-orcid":false,"given":"Felipe","family":"Vargas-Huertas","sequence":"additional","affiliation":[{"name":"Bioactivity & Sustainable Development (BIODESS) Group, Department of Chemistry, University of Costa Rica (UCR), San Jose 2060, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8469-4366","authenticated-orcid":false,"given":"Andr\u00e9s","family":"S\u00e1nchez-Kopper","sequence":"additional","affiliation":[{"name":"CEQIATEC, Department of Chemistry, Costa Rica Institute of Technology (TEC), Cartago 7050, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ahmad Khan, M.S., Ahmad, I., and Chattopadhyay, D. (2019). Herbal Medicine. New Look to Phytomedicine, Elsevier.","DOI":"10.1016\/B978-0-12-814619-4.00001-X"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1475-2891-3-5","article-title":"Apple Phytochemicals and Their Health Benefits","volume":"3","author":"Boyer","year":"2004","journal-title":"Nutr. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1183\/09031936.00086608","article-title":"Molecular mechanisms of cardiovascular disease in OSAHS: The oxidative stress link","volume":"33","author":"Lavie","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jchromb.2005.04.023","article-title":"Oxidative Stress in Brain Aging, Neurodegenerative and Vascular Diseases: An Overview","volume":"827","author":"Mariani","year":"2005","journal-title":"J. Chromatogr. B"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Maurya, P.K., and Dua, K. (2020). Oxidative Stress and Inflammation Can Fuel Cancer. Role of Oxidative Stress in Pathophysiology of Diseases, Springer.","DOI":"10.1007\/978-981-15-1568-2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"713","DOI":"10.5603\/KP.a2018.0071","article-title":"Oxidative Stress and Cardiovascular Disease: New Insights","volume":"76","author":"Pignatelli","year":"2018","journal-title":"Kardiol. Pol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3496043","DOI":"10.1155\/2017\/3496043","article-title":"Oxidative Stress in Infection and Consequent Disease","volume":"2017","author":"Ivanov","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Koch, W. (2019). Dietary Polyphenols\u2014Important Non-Nutrients in the Prevention of Chronic Noncommunicable Diseases. A Systematic Review. Nutrients, 11.","DOI":"10.3390\/nu11051039"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1080\/07315724.2017.1410867","article-title":"Functional Food and Cardiovascular Disease Prevention and Treatment: A Review","volume":"37","author":"Asgary","year":"2018","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5315","DOI":"10.1021\/jf0009293","article-title":"Phenol Antioxidant Quantity and Quality in Foods: Fruits","volume":"49","author":"Vinson","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tungmunnithum, D., Thongboonyou, A., Pholboon, A., and Yangsabai, A. (2018). Flavonoids and Other Phenolic Compounds from Medicinal Plants for Pharmaceutical and Medical Aspects: An Overview. Medicines, 5.","DOI":"10.3390\/medicines5030093"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103861","DOI":"10.1016\/j.jff.2020.103861","article-title":"Proanthocyanidins in Grape Seeds: An Updated Review of Their Health Benefits and Potential Uses in the Food Industry","volume":"67","author":"Unusan","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Patocka, J., Bhardwaj, K., Klimova, B., Nepovimova, E., Wu, Q., Landi, M., Kuca, K., Valis, M., and Wu, W. (2020). Malus Domestica: A Review on Nutritional Features, Chemical Composition, Traditional and Medicinal Value. Plants, 9.","DOI":"10.3390\/plants9111408"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.2174\/1389557519666190311154425","article-title":"Pharmacological Aspects and Potential Use of Phloretin: A Systemic Review","volume":"19","author":"Mariadoss","year":"2019","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/35016151","article-title":"Antioxidant activity of fresh apples","volume":"405","author":"Eberhardt","year":"2000","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Acquavia, M., Pascale, R., Foti, L., Carlucci, G., Scrano, L., Martelli, G., Brienza, M., Coviello, D., Bianco, G., and Lelario, F. (2021). Analytical Methods for Extraction and Identification of Primary and Secondary Metabolites of Apple (Malus domestica) Fruits: A Review. Separations, 8.","DOI":"10.3390\/separations8070091"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1021\/acs.jafc.0c05481","article-title":"Systematic Review of Phenolic Compounds in Apple Fruits: Compositions, Distribution, Absorption, Metabolism, and Processing Stability","volume":"69","author":"Feng","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","first-page":"18","article-title":"A Critical Review on Presence of Polyphenols in Commercial Varieties of Apple Peel, their Extraction and Health Benefits","volume":"6","author":"Shehzadi","year":"2020","journal-title":"Op. Acc. J. Bio. Sci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6038","DOI":"10.1111\/1462-2920.15469","article-title":"Global Analysis of the Apple Fruit Microbiome: Are All Apples the Same?","volume":"23","author":"Abdelfattah","year":"2021","journal-title":"Environ. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/ele.12713","article-title":"Intraspecific Chemical Diversity among Neighbouring Plants Correlates Positively with Plant Size and Herbivore Load but Negatively with Herbivore Damage","volume":"20","author":"Poelman","year":"2017","journal-title":"Ecol. Lett."},{"key":"ref_21","unstructured":"Ram\u00edrez, S.M. (2021). Informe Comercio Exterior del Sector Agropecuario 2019\u20132020, Secretar\u00eda Ejecutiva de Planificaci\u00f3n Sectorial Agropecuaria. SEPSA 2021, 2021\u2013003."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Navarro, M., Moreira, I., Arnaez, E., Quesada, S., Azofeifa, G., Vargas, F., Alvarado, D., and Chen, P. (2018). Polyphenolic characterization and antioxidant activity of Malus domestica and Prunus domestica cultivars from Costa Rica. Foods, 7.","DOI":"10.3390\/foods7020015"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.fbp.2008.03.004","article-title":"Comparison of methods for compositional characterization of grape (Vitis vinifera L.) and apple (Malus domestica) skins","volume":"86","author":"Arnous","year":"2008","journal-title":"Food Bioprod. Process."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kschonsek, J., Wolfram, T., St\u00f6ckl, A., and B\u00f6hm, V. (2018). Polyphenolic Compounds Analysis of Old and New Apple Cultivars and Contribution of Polyphenolic Profile to the In Vitro Antioxidant Capacity. Antioxidants, 7.","DOI":"10.3390\/antiox7010020"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6347","DOI":"10.1021\/jf0346298","article-title":"Polyphenolic Profiles in Eight Apple Cultivars Using High-Performance Liquid Chromatography (HPLC)","volume":"51","author":"Tsao","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.postharvbio.2018.12.015","article-title":"1-Methylcyclopropene (1-MCP), Storage Time, and Shelf Life and Temperature Affect Phenolic Compounds and Antioxidant Activity of \u2018Jonagold\u2019 Apple","volume":"150","author":"Ma","year":"2019","journal-title":"Postharvest Biol. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1021\/jf021115k","article-title":"Detection of Phloridzin in Strawberries (Fragaria \u00d7 Ananassa Duch.) by HPLC\u2212PDA\u2212MS\/MS and NMR Spectroscopy","volume":"51","author":"Hilt","year":"2003","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1016\/j.jplph.2014.08.010","article-title":"Individual Phenolic Response and Peroxidase Activity in Peel of Differently Sun-Exposed Apples in the Period Favorable for Sunburn Occurrence","volume":"171","author":"Zupan","year":"2014","journal-title":"J. Plant. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1021\/tx800227v","article-title":"Apple Polyphenols, Phloretin and Phloridzin: New Trapping Agents of Reactive Dicarbonyl Species","volume":"21","author":"Shao","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0031-9422(90)89030-D","article-title":"Vomifoliol l-0-\u03b2-d-xylopyranosyl-6-o-\u03b2-d-glucopyranoside: A disaccharide glycoside from apple fruit","volume":"29","author":"Schwab","year":"2008","journal-title":"Phytochemistry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1002\/jms.3344","article-title":"Profiles Analysis of Proanthocyanidins in the Argun Nut (Medemia argun -an Ancient Egyptian Palm) by LC-ESI-MS\/MS: Analysis of PACs in M. Argun Nut by LC-ESI-MS\/MS","volume":"49","author":"Hamed","year":"2014","journal-title":"J. Mass Spectrom."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11101-017-9507-3","article-title":"Procyanidins: A Comprehensive Review Encompassing Structure Elucidation via Mass Spectrometry","volume":"17","author":"Rue","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.aca.2004.06.041","article-title":"Analysis of Procyanidins in Pine Bark with Reversed-Phase and Normal-Phase High-Performance Liquid Chromatography\u2013Electrospray Ionization Mass Spectrometry","volume":"522","author":"Karonen","year":"2004","journal-title":"Anal. Chim. Acta"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12020","DOI":"10.1021\/jf402288j","article-title":"Identification of phenolic compounds in plum fruits (Prunus salicina L. and Prunus domestica L.) by HPLC\/MS and characterization of varieties by quantitative phenolic fingerprints","volume":"61","author":"Jaiswal","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S1044-0305(01)00226-4","article-title":"Determination of Flavone, Flavonol, and Flavanone Aglycones by Negative Ion Liquid Chromatography Electrospray Ion Trap Mass Spectrometry","volume":"12","author":"Fabre","year":"2001","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.talanta.2012.07.025","article-title":"Evaluation of Matrix Effect in Determination of Some Bioflavonoids in Food Samples by LC\u2013MS\/MS Method","volume":"99","author":"Prosen","year":"2012","journal-title":"Talanta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.foodchem.2013.11.158","article-title":"Comprehensive identification of walnut polyphenols by liquid chromatography coupled to linear ion trap\u2013Orbitrap mass spectrometry","volume":"152","author":"Regueiro","year":"2014","journal-title":"Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1021\/jf062431s","article-title":"A Screening Method for the Identification of Glycosylated Flavonoids and Other Phenolic Compounds Using a Standard Analytical Approach for All Plant Materials","volume":"55","author":"Lin","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.talanta.2012.11.012","article-title":"Diagnostic Fragment-Ion-Based and Extension Strategy Coupled to DFIs Intensity Analysis for Identification of Chlorogenic Acids Isomers in Flos Lonicerae Japonicae by HPLC-ESI-MSn","volume":"104","author":"Zhang","year":"2013","journal-title":"Talanta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s11418-014-0818-z","article-title":"Structures of acylated sucroses from the flower buds of Prunus mume","volume":"68","author":"Fujimoto","year":"2014","journal-title":"J. Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.foodres.2012.09.038","article-title":"Comprehensive Characterization by UHPLC-ESI-Q-TOF-MS from an Eryngium bourgatii Extract and Their Antioxidant and Anti-Inflammatory Activities","volume":"50","author":"Joven","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1007\/s13197-017-2582-z","article-title":"Distribution of Phenolic Compounds and Antioxidant Capacity in Apples Tissues during Ripening","volume":"54","author":"Alberti","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.jfca.2008.03.004","article-title":"Polyphenol Composition and Total Antioxidant Capacity of Selected Apple Genotypes for Processing","volume":"21","author":"Khanizadeh","year":"2008","journal-title":"J. Food Compost. Anal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"125912","DOI":"10.1016\/j.foodchem.2019.125912","article-title":"Postharvest Changes in Phenolic Compounds and Antioxidant Capacity of Apples Cv. Jonagold Growing in Different Locations in Europe","volume":"310","year":"2020","journal-title":"Food Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s13765-017-0288-6","article-title":"Chemical, Physical, and Sensory Properties of 1-MCP-Treated Fuji Apple (Malus domestica Borkh.) Fruits after Long-Term Cold Storage","volume":"60","author":"Lee","year":"2017","journal-title":"Appl. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Groth, S., Budke, C., Neugart, S., Ackermann, S., Kappenstein, F.-S., Daum, D., and Rohn, S. (2020). Influence of a Selenium Biofortification on Antioxidant Properties and Phenolic Compounds of Apples (Malus domestica). Antioxidants, 9.","DOI":"10.3390\/antiox9020187"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.postharvbio.2007.02.002","article-title":"Phenolic Contents and Other Health and Sensory Related Properties of Apple Fruit (Malus domestica Borkh., Cv. Aroma): Effect of Postharvest UV-B Irradiation","volume":"45","author":"Hagen","year":"2007","journal-title":"Postharvest Biol. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.foodchem.2017.08.010","article-title":"Antioxidant and Antimicrobial Properties of Dried Portuguese Apple Variety (Malus Domestica Borkh. Cv Bravo de Esmolfe)","volume":"240","author":"Pires","year":"2018","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.foodchem.2017.03.111","article-title":"Extraction, Identification, and Antioxidant and Anticancer Tests of Seven Dihydrochalcones from Malus \u2018Red Splendor\u2019 Fruit","volume":"231","author":"Xiao","year":"2017","journal-title":"Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Navarro-Hoyos, M., Arn\u00e1ez-Serrano, E., Quesada-Mora, S., Azofeifa-Cordero, G., Wilhelm-Romero, K., Quir\u00f3s-Fallas, M.I., Alvarado-Corella, D., Vargas-Huertas, F., and S\u00e1nchez-Kopper, A. (2021). Polyphenolic QTOF-ESI MS Characterization and the Antioxidant and Cytotoxic Activities of Prunus domestica Commercial Cultivars from Costa Rica. Molecules, 26.","DOI":"10.3390\/molecules26216493"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1021\/jf047832r","article-title":"Cultivar and Growing Region Determine the Antioxidant Polyphenolic Concentration and Composition of Apples Grown in New Zealand","volume":"53","author":"McGhie","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s00049-016-0213-1","article-title":"Intraspecific Variation of Sesquiterpene Lactones Associated to a Latitudinal Gradient in Smallanthus macroscyphus (Heliantheae: Asteraceae)","volume":"26","author":"Mercado","year":"2016","journal-title":"Chemoecology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1039\/c3fo60470e","article-title":"Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity","volume":"5","author":"Vineetha","year":"2014","journal-title":"Food Funct."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00217-019-03411-z","article-title":"Phytochemical analysis by liquid chromatography of ten old apple varieties grown in Austria and their antioxidative activity","volume":"246","author":"Lachowicz","year":"2020","journal-title":"Eur. Food Res. Technol."},{"key":"ref_55","first-page":"8","article-title":"Polyphenols profile and antioxidant activity of skin and pulp of a rare apple from Marche region (Italy)","volume":"10","author":"Giomaro","year":"2014","journal-title":"Chem. Central J."},{"key":"ref_56","first-page":"288","article-title":"A New Sunburned Apple Category Browning under Conventional and Organic Management: Phenolic Compounds and Antioxidant Capacity in Cold Storage","volume":"92","author":"Yuri","year":"2019","journal-title":"J. Appl. Bot. Food Qual."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1016\/j.foodchem.2009.09.043","article-title":"Antioxidant activity and polyphenol content of aqueous extracts from Colombia Amazonian plants with medicinal use","volume":"119","author":"Lizcano","year":"2010","journal-title":"Food Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1007\/s00394-011-0269-1","article-title":"Procyanidin B2 Induces Nrf2 Translocation and Glutathione S-Transferase P1 Expression via ERKs and P38-MAPK Pathways and Protect Human Colonic Cells against Oxidative Stress","volume":"51","author":"Ramos","year":"2012","journal-title":"Eur. J. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.bbrc.2011.09.014","article-title":"Enhanced Sensitivity of A549 Cells to the Cytotoxic Action of Anticancer Drugs via Suppression of Nrf2 by Procyanidins from Cinnamomi Cortex Extract","volume":"413","author":"Ohnuma","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S102","DOI":"10.1017\/S0007114515000148","article-title":"Fruit and vegetables and cancer risk: A review of 722 southern European studies","volume":"113","author":"Turati","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s394-001-8354-9","article-title":"Vegetables, fruit, antioxidants and cancer: A review of Italian studies","volume":"40","author":"Altieri","year":"2001","journal-title":"Eur. J. Nutr."},{"key":"ref_62","unstructured":"World Health Organization (WHO) (2021, November 25). Cancer Today-Population fact Sheets-Costa Rica. Available online: https:\/\/gco.iarc.fr\/today\/data\/factsheets\/populations\/188-costa-rica-fact-sheets.pdf."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"108999","DOI":"10.1016\/j.biopha.2019.108999","article-title":"Proanthocyanidins: A Comprehensive Review","volume":"116","author":"Rauf","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"243S","DOI":"10.1093\/ajcn\/81.1.243S","article-title":"Bioavailability and Bioefficacy of Polyphenols in Humans. II. Review of 93 Intervention Studies","volume":"81","author":"Williamson","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/carcin\/bgi074","article-title":"Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis","volume":"26","author":"Gosse","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/mnfr.200700513","article-title":"Procyanidin Effects on Oesophageal Adenocarcinoma Cells Strongly Depend on Flavan-3-Ol Degree of Polymerization","volume":"52","author":"Pierini","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Butkeviciute, A., Petrikaite, V., Jurgaityte, V., Liaudanskas, M., and Janulis, V. (2021). Antioxidant, Anti-Inflammatory, and Cytotoxic Activity of Extracts from Some Commercial Apple Cultivars in Two Colorectal and Glioblastoma Human Cell Lines. Antioxidants, 10.","DOI":"10.3390\/antiox10071098"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113158","DOI":"10.1016\/j.indcrop.2020.113158","article-title":"Biological Activity of Phenolics Enriched Extracts from Industrial Apple Pomace","volume":"160","author":"Rana","year":"2021","journal-title":"Ind. Crops Prod."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ejmech.2014.02.010","article-title":"Cytotoxicity and Antimicrobial Activities of Green Synthesized Silver Nanoparticles","volume":"76","author":"Lokina","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103609","DOI":"10.1016\/j.micpath.2019.103609","article-title":"Green synthesis, characterization and antibacterial activity of silver nanoparticles by Malus domestica and its cytotoxic effect on (MCF-7) cell line","volume":"135","author":"Mariadoss","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/1750-3841.15056","article-title":"Phytochemical Profiles, Antioxidant, and Antiproliferative Activities of Four Red-fleshed Apple Varieties in China","volume":"85","author":"Li","year":"2020","journal-title":"J. Food Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.hpj.2019.01.003","article-title":"Phenolic Profile, Antioxidant Activity and Anti-Proliferative Activity of Crabapple Fruits","volume":"5","author":"Han","year":"2019","journal-title":"Hortic. Plant. J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liang, X., Zhu, T., Yang, S., Li, X., Song, B., Wang, Y., Lin, Q., and Cao, J. (2020). Analysis of Phenolic Components and Related Biological Activities of 35 Apple (Malus pumila Mill.) Cultivars. Molecules, 25.","DOI":"10.3390\/molecules25184153"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mahavorasirikul, W., Viyanant, V., Chaijaroenkul, W., Itharat, A., and Na-Bangchang, K. (2010). Cytotoxic Activity of Thai Medicinal Plants against Human Cholangiocarcinoma, Laryngeal and Hepatocarcinoma Cells in Vitro. BMC Complementary Altern. Med., 10.","DOI":"10.1186\/1472-6882-10-55"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1158\/0008-5472.CAN-09-3565","article-title":"Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway","volume":"70","author":"Adams","year":"2010","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"467691","DOI":"10.1093\/ecam\/nen047","article-title":"Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas","volume":"2011","author":"Chatelain","year":"2011","journal-title":"Evid. Based Complementary Altern. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1158\/1535-7163.MCT-06-0014","article-title":"Grape Seed Extract Induces Anoikis and Caspase-Mediated Apoptosis in Human Prostate Carcinoma LNCaP Cells: Possible Role of Ataxia Telangiectasia Mutated\u2013P53 Activation","volume":"5","author":"Kaur","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/01635580802381295","article-title":"Grape Seed Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Carcinoma Cells","volume":"60","author":"Kaur","year":"2008","journal-title":"Nutr. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3390\/ijms13010651","article-title":"Antiproliferative and Apoptotic Effects Triggered by Grape Seed Extract (GSE) versus Epigallocatechin and Procyanidins on Colon Cancer Cell Lines","volume":"13","author":"Dinicola","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"567","DOI":"10.18388\/abp.2017_1599","article-title":"Flavanols from Japanese Quince (Chaenomeles japonica) Fruit Suppress Expression of Cyclooxygenase-2, Metalloproteinase-9, and Nuclear Factor-KappaB in Human Colon Cancer Cells","volume":"64","author":"Owczarek","year":"2017","journal-title":"Acta Biochim. Pol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3233\/JBR190449","article-title":"Bactris guineensis (Arecaceae) Extract: Polyphenol Characterization, Antioxidant Capacity and Cytotoxicity against Cancer Cell Lines","volume":"10","author":"Quesada","year":"2020","journal-title":"J. Berry Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"154164","DOI":"10.1155\/2015\/154164","article-title":"Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer","volume":"2015","author":"Minker","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1111\/j.1742-4658.2007.06010.x","article-title":"The Importance of Polymerization and Galloylation for the Antiproliferative Properties of Procyanidin-Rich Natural Extracts: Antiproliferative Properties of Natural Extracts","volume":"274","author":"Lizarraga","year":"2007","journal-title":"FEBS J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5564312","DOI":"10.1155\/2021\/5564312","article-title":"Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF-\u03b2 Signaling Pathway","volume":"2021","author":"Yang","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.3892\/mmr.2016.5492","article-title":"Suppression of Tumor Cell Proliferation by Quinine via the Inhibition of the Tumor Necrosis Factor Receptor-Associated Factor 6-AKT Interaction","volume":"14","author":"Liu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/carcin\/bgm198","article-title":"Apple Procyanidins Induce Tumor Cell Apoptosis through Mitochondrial Pathway Activation of Caspase-3","volume":"29","author":"Miura","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"22703","DOI":"10.3390\/molecules201219875","article-title":"Phenolic assesment of Uncaria tomentosa L. (Cat\u2019s Claw): Leaves, stem, bark and wood extracts","volume":"20","author":"Navarro","year":"2015","journal-title":"Molecules"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"144","DOI":"10.5344\/ajev.1965.16.3.144","article-title":"Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents","volume":"16","author":"Singleton","year":"1965","journal-title":"Am. J. Enol. Vitic."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Navarro, M., Arnaez, E., Moreira, I., Quesada, S., Azofeifa, G., Wilhelm, K., Vargas, F., and Chen, P. (2019). Polyphenolic Characterization, Antioxidant, and Cytotoxic Activities of Mangifera indica Cultivars from Costa Rica. Foods, 8.","DOI":"10.3390\/foods8090384"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Navarro, M., Arnaez, E., Moreira, I., Hurtado, A., Monge, D., and Monagas, M. (2019). Polyphenolic Composition and Antioxidant Activity of Uncaria tomentosa Commercial Bark Products. Antioxidants, 8.","DOI":"10.3390\/antiox8090339"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.nut.2004.03.025","article-title":"Plant genotype affects total antioxidant capacity and phenolic contents in fruit","volume":"21","author":"Scalzo","year":"2005","journal-title":"Nutrition"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1207\/s15327914nc5302_13","article-title":"Quality assessment of commercial dietary antioxidant products from Vitis vinifera L. grape seeds","volume":"53","author":"Monagas","year":"2005","journal-title":"Nutr. Cancer"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/23\/7367\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:39:46Z","timestamp":1760168386000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/23\/7367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,4]]},"references-count":92,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["molecules26237367"],"URL":"https:\/\/doi.org\/10.3390\/molecules26237367","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,4]]}}}