{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:21:18Z","timestamp":1778019678609,"version":"3.51.4"},"reference-count":96,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["CEECIND\/01507\/2017"],"award-info":[{"award-number":["CEECIND\/01507\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The main goal of this study was to chemically characterize an aqueous S. nigra flower extract and validate it as a bioactive agent. The elderflower aqueous extraction was performed at different temperatures (50, 70 and 90 \u00b0C). The extract obtained at 90 \u00b0C exhibited the highest phenolic content and antiradical activity. Therefore, this extract was analyzed by GC-MS and HPLC-MS, which allowed the identification of 46 compounds, being quercetin and chlorogenic acid derivatives representative of 86% of the total of phenolic compounds identified in hydrophilic fraction of the aqueous extract. Naringenin (27.2%) was the major compound present in the lipophilic fraction. The antiproliferative effects of the S. nigra extract were evaluated using the colon cancer cell lines RKO, HCT-116, Caco-2 and the extract\u2019s antigenotoxic potential was evaluated by the Comet assay in RKO cells. The RKO cells were the most susceptible to S. nigra flower extract (IC50 = 1250 \u00b5g mL\u22121). Moreover, the extract showed antimicrobial activity against Gram-positive bacteria, particularly Staphylococcus aureus and S. epidermidis. These results show that S. nigra-based extracts can be an important dietary source of bioactive phenolic compounds that contribute to health-span improving life quality, demonstrating their potential as nutraceutical, functional foods and\/or cosmetic components for therapeutic purposes.<\/jats:p>","DOI":"10.3390\/biom11081222","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"1222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Chemical Characterization of Sambucus nigra L. Flowers Aqueous Extract and Its Biological Implications"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-4605","authenticated-orcid":false,"given":"Pedro","family":"Ferreira-Santos","sequence":"first","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1079-6893","authenticated-orcid":false,"given":"Helder","family":"Badim","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"\u00c2ngelo C.","family":"Salvador","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Chemistry Department, Campus de Santiago, University of Aveiro, 3810-1930 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5403-8416","authenticated-orcid":false,"given":"Armando J. D.","family":"Silvestre","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Chemistry Department, Campus de Santiago, University of Aveiro, 3810-1930 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6749-7619","authenticated-orcid":false,"given":"S\u00f3nia A. O.","family":"Santos","sequence":"additional","affiliation":[{"name":"CICECO\u2014Aveiro Institute of Materials, Chemistry Department, Campus de Santiago, University of Aveiro, 3810-1930 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-3019","authenticated-orcid":false,"given":"S\u00edlvia M.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica & LAQV-REQUIMTE, Universidade de Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Ana M.","family":"Sousa","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Maria Ol\u00edvia","family":"Pereira","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Cristina Pereira","family":"Wilson","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"},{"name":"Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-0266","authenticated-orcid":false,"given":"Cristina M. R.","family":"Rocha","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4918-3704","authenticated-orcid":false,"given":"Jos\u00e9 Ant\u00f3nio","family":"Teixeira","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8221-419X","authenticated-orcid":false,"given":"Cl\u00e1udia M.","family":"Botelho","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107673","DOI":"10.1016\/j.pharmthera.2020.107673","article-title":"A Natural Product Solution to Aging and Aging-Associated Diseases","volume":"216","author":"Yang","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Ferreira-Santos, P., Ibarz, R., Fernandes, J.-M., Pinheiro, A., Botelho, C., Rocha, C., Teixeira, J., and Mart\u00edn-Belloso, O. (2021). Encapsulated Pine Bark Polyphenolic Extract during Gastrointestinal Digestion: Bioaccessibility, Bioactivity and Oxidative Stress Prevention. Foods, 10.","DOI":"10.3390\/foods10020328"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.3390\/molecules18011227","article-title":"A Review on Anti-Inflammatory Activity of Monoterpenes","volume":"18","author":"Andrade","year":"2013","journal-title":"Molecules"},{"key":"ref_4","first-page":"1","article-title":"Monoterpenes with Analgesic Activity-A Systematic Review","volume":"27","author":"Quintans","year":"2012","journal-title":"Phytother. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"110774","DOI":"10.1016\/j.biopha.2020.110774","article-title":"Pharmacological Insights and Prediction of Lead Bioactive Isolates of Dita Bark through Experimental and Computer-Aided Mechanism","volume":"131","author":"Khan","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1021\/acs.jafc.9b02155","article-title":"Low-Molecular Weight Metabolites from Polyphenols as Effectors for Attenuating Neuroinflammation","volume":"68","author":"Carregosa","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110189","DOI":"10.1016\/j.foodres.2021.110189","article-title":"Role of Dietary Polyphenols on Gut Microbiota, their Metabolites and Health Benefits","volume":"142","author":"Aravind","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100850","DOI":"10.1016\/j.fbio.2020.100850","article-title":"The Anti-Inflammatory and Antioxidant Properties of Chickpea Hull Phenolic Extracts","volume":"40","author":"Mahbub","year":"2021","journal-title":"Food Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Akkol, E.K., Gen\u00e7, Y., Karpuz, B., Sobarzo-S\u00e1nchez, E., and Capasso, R. (2020). Coumarins and Coumarin-Related Compounds in Pharmacotherapy of Cancer. Cancers, 12.","DOI":"10.3390\/cancers12071959"},{"key":"ref_10","unstructured":"EU (2020). Farm to Fork Strategy: For a Fair, Healthy and Environmentally-Friendly Food System, EU. Available online: https:\/\/ec.europa.eu\/food\/sites\/food\/files\/safety\/docs\/f2f_action-plan_2020_strategy-info_en.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1021\/acs.jafc.5b03092","article-title":"Edible Flowers: A Rich Source of Phytochemicals with Antioxidant and Hypoglycemic Properties","volume":"64","author":"Loizzo","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"584","DOI":"10.3390\/ijms18030584","article-title":"Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264. 7 Macrophages and Dendritic Cells","volume":"18","author":"Thanh","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ferreira, S.S., Silva, A.M., and Nunes, F.M. (2020). Sambucus nigra L. Fruits and Flowers: Chemical Composition and Related Bioactivities. Food Rev. Int., 1\u201329.","DOI":"10.1080\/87559129.2020.1788578"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Przybylska-Balcerek, A., Szablewski, T., Szwajkowska-Micha\u0142ek, L., \u015awierk, D., Cegielska-Radziejewska, R., Krejpcio, Z., Suchowilska, E., Tomczyk, \u0141., and Stuper-Szablewska, K. (2021). Sambucus nigra Extracts\u2013Natural Antioxidants and Antimicrobial Compounds. Molecules, 26.","DOI":"10.3390\/molecules26102910"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.foodchem.2011.07.127","article-title":"Estimation of Antiradical Properties of Antioxidants Using DPPH Assay: A Critical Review and Results","volume":"130","author":"Mishra","year":"2012","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.indcrop.2010.10.006","article-title":"High Value Triterpenic Compounds from the Outer Barks of Several Eucalyptus Species Cultivated in Brazil and in Portugal","volume":"33","author":"Domingues","year":"2010","journal-title":"Ind. Crop. Prod."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1021\/bm500524s","article-title":"The Potential of Cellulose Nanocrystals in Tissue Engineering Strategies","volume":"15","author":"Domingues","year":"2014","journal-title":"Biomacromolecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1365\/s10337-008-0533-6","article-title":"Determination of Oleanolic, Betulinic and Ursolic Acid in Lamiaceae and Mass Spectral Fragmentation of Their Trimethylsilylated Derivatives","volume":"67","year":"2008","journal-title":"Chromatographia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/j.foodres.2013.09.017","article-title":"The Ripe Pulp of Mangifera Indica L.: A Rich Source of Phytosterols and Other Lipophilic Phytochemicals","volume":"54","author":"Vilela","year":"2013","journal-title":"Food Res. Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108979","DOI":"10.1016\/j.foodres.2020.108979","article-title":"\u03b2-Lactoglobulin Micro- and Nanostructures as Bioactive Compounds Vehicle: In Vitro Studies","volume":"131","author":"Martins","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1385\/MB:26:3:249","article-title":"The Comet Assay for DNA Damage and Repair: Principles, Applications, and Limitations","volume":"26","author":"Collins","year":"2004","journal-title":"Mol. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7465","DOI":"10.1021\/jf100082p","article-title":"Polyphenolic Compounds from Salvia Species Protect Cellular DNA from Oxidation and Stimulate DNA Repair in Cultured Human Cells","volume":"58","author":"Ramos","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","unstructured":"CLSI (2020). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [30th ed.]. Supplement M100."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Oliveira, C.S.D., Moreira, P., Resende, J., Cruz, M.T., Pereira, C.M.F., Silva, A.M.S., Santos, S.A.O., and Silvestre, A.J.D. (2020). Characterization and Cytotoxicity Assessment of the Lipophilic Fractions of Different Morphological Parts of Acacia dealbata. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051814"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.jff.2014.07.012","article-title":"Advanced Research on the Antioxidant and Health Benefit of Elderberry (SAMBUCUS nigra) in food\u2014A Review","volume":"18","author":"Sidor","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.foodchem.2014.01.028","article-title":"In vitro Antioxidant Properties and Anthocyanin Compositions of Elderberry Extracts","volume":"155","year":"2014","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ferreira-Santos, P., Zanuso, E., Genisheva, Z., Rocha, C., and Teixeira, J. (2020). Green and Sustainable Valorization of Bioactive Phenolic Compounds from Pinus By-Products. Molecules, 25.","DOI":"10.3390\/molecules25122931"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/10715762.2017.1322205","article-title":"Antioxidant Therapy for Management of Oxidative Stress Induced Hypertension","volume":"51","author":"Ahmad","year":"2017","journal-title":"Free. Radic. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hueda, M.C. (2017). Polyphenols: Food Sources and Health Benefits. Functional Food-Improve Health through Adequate Food, IntechOpen.","DOI":"10.5772\/66263"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Santos, P.M.F., Genisheva, Z., Botelho, C., Santos, J., Ramos, C., Teixeira, J.A., and Rocha, C.M. (2020). Unravelling the Biological Potential of Pinus pinaster Bark Extracts. Antioxidants, 9.","DOI":"10.3390\/antiox9040334"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.indcrop.2012.07.066","article-title":"The Phenolic Content and Antioxidant Activity of Infusions from Mediterranean Medicinal Plants","volume":"43","author":"Gomes","year":"2013","journal-title":"Ind. Crop. Prod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.lwt.2005.01.005","article-title":"The Antioxidant Properties of Alcoholic Extracts from Sambucus nigra L. (Antioxidant Properties of Extracts)","volume":"39","author":"Dawidowicz","year":"2006","journal-title":"LWT"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.foodchem.2015.10.139","article-title":"Influence of Heat Treatment on Antioxidant Capacity and (Poly)Phenolic Compounds of Selected Vegetables","volume":"197","author":"Ludwig","year":"2016","journal-title":"Food Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s11130-016-0594-x","article-title":"The Phenolic Contents and Antioxidant Activities of Infusions of Sambucus nigra L.","volume":"72","author":"Viapiana","year":"2017","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.jff.2014.07.009","article-title":"Short Communications Evaluation of the Total Antioxidant Capacity and Antioxidant Compounds Of Different Solvent Extracts of Chilgoza Pine Nuts (Pinus Gerardiana )","volume":"18","author":"Hoon","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8816","DOI":"10.1021\/acssuschemeng.9b00780","article-title":"Moderate Electric Fields as a Potential Tool for Sustainable Recovery of Phenolic Compounds from Pinus Pinaster Bark","volume":"7","author":"Santos","year":"2019","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tundis, R., Ursino, C., Bonesi, M., Loizzo, M.R., Sicari, V., Pellican\u00f2, T., Manfredi, I.L., Figoli, A., and Cassano, A. (2019). Flower and Leaf Extracts of Sambucus nigra L.: Application of Membrane Processes to Obtain Fractions with Antioxidant and Antityrosinase Properties. Membranes, 9.","DOI":"10.3390\/membranes9100127"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Stillwell, W. (2013). An Introduction to Biological Membranes: From Bilayers to Rafts, Elsevier B.V.","DOI":"10.1016\/B978-0-444-52153-8.00001-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/s11655-014-1960-x","article-title":"A Review on Pharmacological and Analytical Aspects of Naringenin","volume":"24","author":"Patel","year":"2014","journal-title":"Chin. J. Integr. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.lfs.2018.10.066","article-title":"Pharmacokinetic, Pharmacodynamic and Formulations Aspects of Naringenin: An Update","volume":"215","author":"Joshi","year":"2018","journal-title":"Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/10286021003620226","article-title":"Peroxynitrite and Hemoglobin-Mediated Nitrative\/Oxidative modification of Human Plasma Protein: Effects of Some Flavonoids","volume":"12","author":"Wang","year":"2010","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jnutbio.2016.03.013","article-title":"The Citrus Flavonone Naringenin Reduces Lipopolysaccharide-Induced Inflammatory Pain and Leukocyte Recruitment by Inhibiting NF-\u03baB Activation","volume":"33","author":"Zarpelon","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1248\/bpb.28.527","article-title":"Inhibitory Effects of Naringenin on Tumor Growth in Human Cancer Cell Lines and Sarcoma S-180-Implanted Mice","volume":"28","author":"Kanno","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1039\/C1CC10778J","article-title":"A Single-Molecule Study of the Inhibition Effect of Naringenin on Transforming Growth Factor-\u03b2 Ligand\u2013Receptor Binding","volume":"47","author":"Yang","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_45","first-page":"1","article-title":"Naringenin Ameliorated Kidney Injury through Let-7a\/TGFBR1 Signaling in Diabetic Nephropathy","volume":"2016","author":"Yan","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1211\/jpp.58.3.0013","article-title":"Inhibition of Rat vas Deferens Contractions by Flavonoids in-Vitro","volume":"58","author":"Capasso","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.biocel.2005.10.002","article-title":"Inhibition of Intestinal and Renal Na+-Glucose Cotransporter by Naringenin","volume":"38","author":"Li","year":"2006","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.pnpbp.2010.06.024","article-title":"Involvement of Monoaminergic System in the Antidepressant-Like Effect of the Flavonoid Naringenin in Mice","volume":"34","author":"Yi","year":"2010","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.brainresbull.2020.12.003","article-title":"Naringenin improves Depressive- and Anxiety-Like Behaviors in Mice Exposed to Repeated Hypoxic Stress through Modulation of Oxido-Inflammatory Mediators and NF-kB\/BDNF Expressions","volume":"169","author":"Olugbemide","year":"2021","journal-title":"Brain Res. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"173535","DOI":"10.1016\/j.ejphar.2020.173535","article-title":"Naringenin and Naringin in Cardiovascular Disease Prevention: A Preclinical Review","volume":"887","author":"Moghaddam","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1021\/jf506005b","article-title":"Traditional Elderflower Beverages: A Rich Source of Phenolic Compounds with High Antioxidant Activity","volume":"63","author":"Samoticha","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.indcrop.2015.03.082","article-title":"Lipophilic Phytochemicals from Elderberries (Sambucus nigra L.): Influence of Ripening, Cultivar and Season","volume":"71","author":"Salvador","year":"2015","journal-title":"Ind. Crop. Prod."},{"key":"ref_53","unstructured":"Food and Agriculture Organization of the United Nations (FAO) (2010). Fats and Fatty Acids in Human Nutrition, FAO."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.fct.2012.02.004","article-title":"Characterization of Phenolic Compounds in Flowers of Wild Medicinal Plants from Northeastern Portugal","volume":"50","author":"Barros","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1556\/AAlim.2010.0010","article-title":"The Stability of Rutin and Chlorogenic Acid during the Processing of Black Elder (Sambucus nigra) Inflorescence","volume":"40","year":"2011","journal-title":"Acta Aliment."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijpharm.2010.09.035","article-title":"In Vitro and In Vivo Antioxidant Properties of Chlorogenic Acid and Caffeic Acid","volume":"403","author":"Sato","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.2174\/1381612826666200212115826","article-title":"Caffeoylquinic Acids with Potential Biological Activity from Plant In Vitro Cultures as Alternative Sources of Valuable Natural Products","volume":"26","author":"Wieczfinska","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_58","first-page":"683","article-title":"Anti-Inflammatory Properties of Plant Flavonoids. Effects of Rutin, Quercetin and Hesperidin on Adjuvant Arthritis in Rat","volume":"56","author":"Guardia","year":"2001","journal-title":"II Farm."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.taap.2005.09.007","article-title":"Effect of Ginkgo Biloba Extract on Procarcinogen-Bioactivating Human CYP1 Enzymes: Identification of Isorhamnetin, Kaempferol, and Quercetin as Potent Inhibitors of CYP1B1","volume":"213","author":"Chang","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wang, J., Fang, X., Ge, L., Cao, F., Zhao, L., Wang, Z., and Xiao, W. (2018). Antitumor, Antioxidant and Anti-Inflammatory Activities of Kaempferol and its Corresponding Glycosides and the Enzymatic Preparation of Kaempferol. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197563"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S2222-1808(15)61024-6","article-title":"Quercetin: A Wonder Bioflavonoid with Therapeutic Potential in Disease Management","volume":"6","author":"Gupta","year":"2016","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5490","DOI":"10.1021\/jf0202133","article-title":"Antioxidant Effects of Isorhamnetin 3,7-di-O-\u03b2-D-Glucopyranoside Isolated from Mustard Leaf (Brassica juncea) in rats with Streptozotocin-Induced Diabetes","volume":"50","author":"Yokozawa","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.3892\/mmr.2015.4269","article-title":"Isorhamnetin Inhibits Cell Proliferation and Induces Apoptosis in Breast Cancer via Akt and Mitogen-Activated Protein Kinase Kinase Signaling Pathways","volume":"12","author":"Yingchun","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.biopha.2018.08.006","article-title":"Colorectal Cancer and Medicinal Plants: Principle Findings from Recent Studies","volume":"107","author":"Benarba","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1089\/jmf.2006.9.498","article-title":"A Comparative Evaluation of the Anticancer Properties of European and American Elderberry Fruits","volume":"9","author":"Thole","year":"2006","journal-title":"J. Med. Food"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.foodchem.2015.11.017","article-title":"Gastrointestinal Digested Sambucus nigra L. Fruit Extract Protects In Vitro Cultured Human Colon Cells against Oxidative Stress","volume":"197","author":"Olejnik","year":"2016","journal-title":"Food Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0378-8741(02)00116-2","article-title":"Anticancer and Antithrombin Activity of Russian Plants","volume":"81","author":"Goun","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.1021\/jf8005917","article-title":"Structure\u2212Function Relationships of Anthocyanins from Various Anthocyanin-Rich Extracts on the Inhibition of Colon Cancer Cell Growth","volume":"56","author":"Jing","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Jesus, M.S., Carvalho, A.C., Teixeira, J.A., Domingues, L., and Pereira-Wilson, C. (2020). Ohmic Heating Extract of Vine Pruning Residue Has Anti-Colorectal Cancer Activity and Increases Sensitivity to the Chemotherapeutic Drug 5-FU. Foods, 9.","DOI":"10.3390\/foods9081102"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chiang, E., Tsai, S.-Y., Kuo, Y.-H., Pai, M.-H., Chiu, H.-L., Rodriguez, R.L., and Tang, F.-Y. (2014). Caffeic Acid Derivatives Inhibit the Growth of Colon Cancer: Involvement of the PI3-K\/Akt and AMPK Signaling Pathways. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099631"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1016\/j.phymed.2016.09.011","article-title":"Inhibitory Effect of Quercetin on Colorectal Lung Metastasis through Inducing Apoptosis, and Suppression of Metastatic Ability","volume":"23","author":"Kee","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"161","DOI":"10.15430\/JCP.2014.19.3.161","article-title":"Kaempferol Downregulates Insulin-like Growth Factor-I Receptor and ErbB3 Signaling in HT-29 Human Colon Cancer Cells","volume":"19","author":"Lee","year":"2014","journal-title":"J. Cancer Prev."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bhia, M., Motallebi, M., Abadi, B., Zarepour, A., Pereira-Silva, M., Saremnejad, F., Santos, A., Zarrabi, A., Melero, A., and Jafari, S. (2021). Naringenin Nano-Delivery Systems and Their Therapeutic Applications. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020291"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Buhrmann, C., Kunnumakkara, A.B., Popper, B., Majeed, M., Aggarwal, B.B., and Shakibaei, M. (2020). Calebin A Potentiates the Effect of 5-FU and TNF-\u03b2 (Lymphotoxin \u03b1) against Human Colorectal Cancer Cells: Potential Role of NF-\u03baB. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072393"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1535370218824538","article-title":"Evidence that TNF-\u03b2 induces Proliferation in Colorectal Cancer Cells and Resveratrol can Down-Modulate it","volume":"244","author":"Buhrmann","year":"2019","journal-title":"Exp. Biol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-015-1291-0","article-title":"Curcumin Potentiates Antitumor Activity of 5-Fluorouracil in a 3D Alginate Tumor Microenvironment of Colorectal Cancer","volume":"15","author":"Shakibaei","year":"2015","journal-title":"BMC Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.toxlet.2008.01.001","article-title":"Antigenotoxic Effects of Quercetin, Rutin and Ursolic acid on HepG2 Cells: Evaluation by the Comet Assay","volume":"177","author":"Ramos","year":"2008","journal-title":"Toxicol. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1080\/01635581.2015.1004736","article-title":"Effects of Caffeic and 5-Caffeoylquinic Acids on Cell Viability and Cellular Uptake in Human Colon Adenocarcinoma Cells","volume":"67","author":"Murad","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"108612","DOI":"10.1016\/j.biopha.2019.108612","article-title":"Luteolin, a Flavonoid, as an Anticancer Agent: A Review","volume":"112","author":"Imran","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2174\/156800908786241050","article-title":"Luteolin, a Flavonoid with Potential for Cancer Prevention and Therapy","volume":"8","author":"Lin","year":"2008","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1016\/j.lfs.2006.06.042","article-title":"Phenolic Compounds Protect HepG2 cells from Oxidative Damage: Relevance of Glutathione Levels","volume":"79","author":"Lima","year":"2006","journal-title":"Life Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.2174\/0929867322666150530210522","article-title":"Insights on Antimicrobial Resistance, Biofilms and the Use of Phytochemicals as new Antimicrobial Agents","volume":"22","author":"Borges","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.micres.2016.12.003","article-title":"Phytochemicals for Human Disease: An Update on Plant-Derived Compounds Antibacterial Activity","volume":"196","author":"Barbieri","year":"2017","journal-title":"Microbiol. Res."},{"key":"ref_84","first-page":"1","article-title":"Inhibition of Penicillin-Binding Protein 2a (PBP2a) in Methicillin Resistant Staphylococcus Aureus (MRSA) by Combination of Ampicillin and a Bioactive Fraction from Duabanga Grandiflora","volume":"15","author":"Santiago","year":"2015","journal-title":"BMC Complement. Altern. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mets\u00e4muuronen, S., and Sir\u00e9n, H. (2019). Bioactive Phenolic Compounds, Metabolism and Properties: A Review on Valuable Chemical Compounds in Scots Pine and Norway Spruce, Springer.","DOI":"10.1007\/s11101-019-09630-2"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"198","DOI":"10.2174\/1574891X08666131210124649","article-title":"Novel Quercetin Glycosides as Potent Anti-MRSA and Anti-VRE Agents","volume":"8","author":"Hossion","year":"2014","journal-title":"Recent Patents Anti-Infect. Drug Discov."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7933","DOI":"10.3390\/molecules15117933","article-title":"Flavonoids from Halostachys Caspica and Their Antimicrobial and Antioxidant Activities","volume":"15","author":"Liu","year":"2010","journal-title":"Molecules"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.lwt.2015.08.024","article-title":"5-O-Caffeoylquinic Acid: A Spectroscopic Study and Biological Screening for Antimicrobial Activity","volume":"65","author":"Bajko","year":"2016","journal-title":"LWT"},{"key":"ref_89","first-page":"1","article-title":"Phenolic Compounds and In Vitro Antibacterial and Antioxidant Activities of Three Tropic Fruits: Persimmon, Guava, and Sweetsop","volume":"2016","author":"Fu","year":"2016","journal-title":"BioMed. Res. Int."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/cid\/ciu235","article-title":"Is asymptomatic Bacteriuria a Risk Factor for Prosthetic Joint Infection?","volume":"59","author":"Sousa","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s10930-015-9609-y","article-title":"Inhibition of Staphylococcus Aureus PriA Helicase by Flavonol Kaempferol","volume":"34","author":"Huang","year":"2015","journal-title":"Protein J."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Silva, B., Cadavez, V., Ferreira-Santos, P., Alves, M., Ferreira, I., Barros, L., Teixeira, J., and Gonzales-Barron, U. (2021). Chemical Profile and Bioactivities of Extracts from Edible Plants Readily Available in Portugal. Foods, 10.","DOI":"10.3390\/foods10030673"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.lwt.2007.01.016","article-title":"Antimicrobial Activity of Some Plant Extracts and Essential Oils against Foodborne Pathogens In Vitro and on the Fate of Inoculated Pathogens in Chocolate","volume":"41","author":"Kotzekidou","year":"2008","journal-title":"LWT"},{"key":"ref_94","first-page":"241","article-title":"Comprehensive Review of Antimicrobial Activities of Plant Flavonoids","volume":"18","author":"Bartoszewski","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1046\/j.1365-2672.2001.01271.x","article-title":"Antimicrobial Properties of Phenolic Compounds from Berries","volume":"90","author":"Nohynek","year":"2001","journal-title":"J. Appl. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1351\/PAC-CON-09-01-08","article-title":"Antifungal Action of Chlorogenic Acid against Pathogenic Fungi, Mediated by Membrane Disruption","volume":"82","author":"Sung","year":"2010","journal-title":"Pure Appl. Chem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/8\/1222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:45:24Z","timestamp":1760165124000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/8\/1222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,17]]},"references-count":96,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["biom11081222"],"URL":"https:\/\/doi.org\/10.3390\/biom11081222","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,17]]}}}