{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:56:40Z","timestamp":1770742600993,"version":"3.49.0"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000041"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000041"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>This study investigates the possibility of valorizing coffee silverskin through the recovery of its bioactive compounds using a sustainable extraction method that could be industrially applied. For that, aqueous extracts were prepared using ultrasonic-assisted extraction (laboratorial scale) and, for comparison, a scale-up of the process was developed using the Multi-frequency Multimode Modulated technology. A concentration procedure at the pilot scale was also tested. The three types of extracts obtained were characterized regarding caffeine and chlorogenic acids contents, and the effects on intestinal glucose and fructose uptake (including sugar transporters expression) in human intestinal epithelial (Caco-2) cells were ascertained. The phytochemical contents of the extracts prepared at the laboratory and pilot scale were comparable (caffeine: 27.7 vs. 29.6 mg\/g freeze-dried extract; 3-, 4-, and 5-caffeoylquinic acids: 0.19 vs. 0.31, 0.15 vs. 0.42, and 1.04 vs. 1.98 mg\/g, respectively; 4- and 5- feruloylquinic acids: 0.39 vs. 0.43 and 1.05 vs. 1.32 mg\/g, respectively). Slight differences were noticed according to the extracts preparation steps, but in general, all the extracts promoted significant inhibitions of [1,2-3H(N)]-deoxy-D-glucose and 14C-D-fructose uptake, which resulted mainly from a decrease on the facilitative glucose transporter 2 (GLUT2) and sodium-glucose linked transporter 1 (SGLT1) genes expression but not on the expression of the facilitative glucose transporter 5 (GLUT5) gene. Moreover, a synergistic effect of caffeine and 5-caffeoylquinic acid on sugars uptake was found. The results clearly show that the Multi-frequency Multimode Modulated technology is a viable option to be applied at an industrial level to recover bioactive components from silverskin and obtain extracts with antidiabetic potential that could be used to develop functional food products or dietary supplements.<\/jats:p>","DOI":"10.3390\/foods11121671","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:22:39Z","timestamp":1654820559000},"page":"1671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Valorizing Coffee Silverskin Based on Its Phytochemicals and Antidiabetic Potential: From Lab to a Pilot Scale"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-1622","authenticated-orcid":false,"given":"Juliana A. Barreto","family":"Peixoto","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2600-8599","authenticated-orcid":false,"given":"Nelson","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"},{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Susana","family":"Machado","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"}]},{"given":"Anabela S. G.","family":"Costa","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"}]},{"given":"Helder","family":"Puga","sequence":"additional","affiliation":[{"name":"CMEMS-UMinho, Department of Mechanical Engineering, University of Minho, Campus de Azur\u00e9m, 4800-058 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-6596","authenticated-orcid":false,"given":"Maria Beatriz P. P.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0525-3416","authenticated-orcid":false,"given":"F\u00e1tima","family":"Martel","sequence":"additional","affiliation":[{"name":"Unit of Biochemistry, Department of Biomedicine, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), University of Porto, R. Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5053-513X","authenticated-orcid":false,"given":"Rita C.","family":"Alves","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.scitotenv.2018.07.201","article-title":"Coffea canephora silverskin from different geographical origins: A comparative study","volume":"645","author":"Bessada","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s11947-011-0565-z","article-title":"Production, composition, and application of coffee and its industrial residues","volume":"4","author":"Mussatto","year":"2011","journal-title":"Food Bioprocess Technol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jclepro.2017.08.231","article-title":"Multi-frequency multimode modulated technology as a clean, fast, and sustainable process to recover antioxidants from a coffee by-product","volume":"168","author":"Puga","year":"2017","journal-title":"J. Clean. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.foodchem.2017.03.106","article-title":"Nutritional, chemical and antioxidant\/pro-oxidant profiles of silverskin, a coffee roasting by-product","volume":"267","author":"Costa","year":"2018","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131188","DOI":"10.1016\/j.foodchem.2021.131188","article-title":"Coffee silverskin: Characterization of B-vitamins, macronutrients, minerals and phytosterols","volume":"372","author":"Nzekoue","year":"2022","journal-title":"Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/bs.afnr.2019.10.002","article-title":"Chemical composition and health properties of coffee and coffee by-products","volume":"91","author":"Pagnoncelli","year":"2020","journal-title":"Adv. Food Nutr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1080\/87559129.2019.1573432","article-title":"The effect of dietary polyphenols on intestinal absorption of glucose and fructose: Relation with obesity and type 2 diabetes","volume":"35","author":"Loureiro","year":"2019","journal-title":"Food Rev. Int."},{"key":"ref_8","unstructured":"Watson, R. (2019). Coffee intake and obesity. Nutrition in the Prevention and Treatment of Abdominal Obesity, Academic Press. [2nd ed.]."},{"key":"ref_9","unstructured":"Preedy, V.R. (2015). Chlorogenic acid in whole body and tissue-specific glucose regulation. Coffee in Health and Disease Prevention, Academic Press."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.semarthrit.2019.10.001","article-title":"Association of glucose homeostasis and metabolic syndrome with knee cartilage defects and cartilage volume in young adults","volume":"50","author":"Meng","year":"2020","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"71","DOI":"10.20945\/2359-3997000000199","article-title":"High-sugar diet leads to obesity and metabolic diseases in ad libitum-fed rats irrespective of caloric intake","volume":"64","author":"Fernandes","year":"2020","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Seo, E.H., Kim, H., and Kwon, O. (2019). Association between total sugar intake and metabolic syndrome in middle-aged Korean men and women. Nutrients, 11.","DOI":"10.3390\/nu11092042"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"928","DOI":"10.2174\/15701611113116660174","article-title":"Dietary regulation of glucose metabolism in metabolic syndrome","volume":"11","author":"Bullo","year":"2014","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1743-7075-8-50","article-title":"Dietary fructose and risk of metabolic syndrome in adults: Tehran lipid and glucose study","volume":"8","author":"Bahadoran","year":"2011","journal-title":"Nutr. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Taskinen, M.R., Packard, C.J., and Bor\u00e9n, J. (2019). Dietary fructose and the metabolic syndrome. Nutrients, 11.","DOI":"10.3390\/nu11091987"},{"key":"ref_16","unstructured":"Preedy, V.R. (2015). Caffeine, insulin resistance, and hypertension. Coffee in Health and Disease Prevention, Academic Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ajcn\/78.4.728","article-title":"Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: Glycemic effects of chlorogenic acid and caffeine","volume":"78","author":"Johnston","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","first-page":"23","article-title":"Caffeine, glucose metabolism, and type 2 diabetes","volume":"1","author":"Lane","year":"2011","journal-title":"J. Caf. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1017\/S0007114518000260","article-title":"Postprandial glycaemic and lipaemic responses to chronic coffee consumption may be modulated by CYP1A2 polymorphisms","volume":"119","author":"Robertson","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1590\/S0100-40422009000800031","article-title":"Benef\u00edcios do caf\u00e9 na sa\u00fade: Mito ou realidade?","volume":"32","author":"Alves","year":"2009","journal-title":"Qu\u00edm. Nova"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1039\/C7FO00388A","article-title":"How coffee affects metabolic syndrome and its components","volume":"8","author":"Baspinar","year":"2017","journal-title":"Food Funct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1039\/C4FO00042K","article-title":"Coffee: Biochemistry and potential impact on health","volume":"5","author":"Ludwig","year":"2014","journal-title":"Food Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tifs.2022.03.013","article-title":"Phenolic compounds from coffee by-products: Extraction and application in the food and pharmaceutical industries","volume":"123","author":"Bondam","year":"2022","journal-title":"Trends Food Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Iriondo-De Hond, A., Iriondo-De Hond, M., and del Castillo, M.D. (2020). Applications of compounds from coffee processing by-products. Biomolecules, 10.","DOI":"10.3390\/biom10091219"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12393-019-09206-y","article-title":"Green solvents for the extraction of high added-value compounds from agri-food waste","volume":"12","author":"Rubio","year":"2020","journal-title":"Food Eng. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.ultsonch.2016.06.035","article-title":"Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review","volume":"34","author":"Chemat","year":"2017","journal-title":"Ultrason. Sonochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Prot."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1039\/C8TX00183A","article-title":"The effect of oxidative stress upon intestinal sugar transport: An in vitro study using human intestinal epithelial (Caco-2) cells","volume":"7","author":"Andrade","year":"2018","journal-title":"Toxicol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Medina-Torres, N., Ayora-Talavera, T., Espinosa-Andrews, H., S\u00e1nchez-Contreras, A., and Pacheco, N. (2017). Ultrasound assisted extraction for the recovery of phenolic compounds from vegetable sources. Agronomy, 7.","DOI":"10.3390\/agronomy7030047"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ifset.2007.04.014","article-title":"Applications and opportunities for ultrasound assisted extraction in the food industry\u2014A review","volume":"9","author":"Vilkhu","year":"2008","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.indcrop.2014.01.006","article-title":"Optimization of antioxidants extraction from coffee silverskin, a roasting by-product, having in view a sustainable process","volume":"53","author":"Costa","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.foodchem.2012.05.078","article-title":"High antioxidant activity of coffee silverskin extracts obtained by the treatment of coffee silverskin with subcritical water","volume":"135","author":"Narita","year":"2012","journal-title":"Food Chem."},{"key":"ref_34","unstructured":"Preedy, V.R. (2015). Chlorogenic acids from coffee. Coffee in Health and Disease Prevention, Academic Press."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11101-018-9592-y","article-title":"Recent advances in extraction and analysis procedures of natural chlorogenic acids","volume":"18","author":"Wianowska","year":"2019","journal-title":"Phytochem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1021\/jf0518305","article-title":"Chlorogenic acids and lactones in regular and water-decaffeinated arabica coffees","volume":"54","author":"Farah","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","unstructured":"Galanakis, C.M. (2017). State of the art in coffee processing by-products. Handbook of Coffee Processing By-Products, Academic Press."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Habtemariam, S. (2019). Chemical and pharmacological evidences for coffee as a modulator of type 2 diabetes and metabolic syndrome. Medicinal Foods as Potential Therapies for Type-2 Diabetes and Associated Diseases\u2013The Chemical and Pharmacological Basis of Their Action, Academic Press.","DOI":"10.1016\/B978-0-08-102922-0.00021-3"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1093\/jn\/133.11.3529","article-title":"Quinides of roasted coffee enhance insulin action in conscious rats","volume":"133","author":"Shearer","year":"2003","journal-title":"J. Nutr."},{"key":"ref_40","unstructured":"Preedy, V.R. (2015). Melanoidins in coffee. Coffee in Health and Disease Prevention, Academic Press."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"De la Cruz, S.T., Iriondo-DeHond, A., Herrera, T., Lopez-Tofi\u00f1o, Y., Galvez-Roble\u00f1o, C., Prodanov, M., Velazquez-Escobar, F., Abalo, R., and del Castillo, M.D. (2019). An assessment of the bioactivity of coffee silverskin melanoidins. Foods, 8.","DOI":"10.3390\/foods8020068"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"126309","DOI":"10.1016\/j.foodchem.2020.126309","article-title":"Bioactivity of food melanoidins is mediated by gut microbiota","volume":"316","author":"Rajakaruna","year":"2020","journal-title":"Food Chem."},{"key":"ref_43","first-page":"1005","article-title":"Coffee silverskin: A low-cost substracte for bioproduction of high-value health promoting products","volume":"1","author":"Martirosyan","year":"2017","journal-title":"Ann. Nutr. Food Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nunes, M.A., Reszczynski, F., P\u00e1scoa, R.N.M.J., Costa, A.S.G., Alves, R.C., and Oliveira, M.B.P.P. (2021). Influence of olive pomace blending on antioxidant activity: Additive, synergistic, and antagonistic effects. Molecules, 26.","DOI":"10.3390\/molecules26010169"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3892\/br.2021.1449","article-title":"Coffea arabica bean extract inhibits glucose transport and disaccharidase activity in Caco-2 cells","volume":"15","author":"Ontawong","year":"2021","journal-title":"Biomed. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1093\/jn\/119.11.1698","article-title":"Dietary phenolic compounds: Inhibition of Na+-dependent D-glucose uptake in rat intestinal brush border membrane vesicles","volume":"119","author":"Welsch","year":"1989","journal-title":"J. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.jff.2017.07.032","article-title":"Effect of dietary polyphenols on fructose uptake by human intestinal epithelial (Caco-2) cells","volume":"36","author":"Andrade","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"E227","DOI":"10.1152\/ajpendo.90245.2008","article-title":"Regulation of the fructose transporter GLUT5 in health and disease","volume":"295","author":"Douard","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.2337\/diabetes.54.10.3056","article-title":"Apical GLUT2: A major pathway of intestinal sugar absorption","volume":"54","author":"Kellett","year":"2005","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.nutr.28.061807.155518","article-title":"Sugar absorption in the intestine: The role of GLUT2","volume":"28","author":"Kellett","year":"2008","journal-title":"Ann. Rev. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jnutbio.2012.06.006","article-title":"Glucose as a fetal nutrient: Dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation","volume":"24","author":"Novakovic","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3583067","DOI":"10.1155\/2019\/3583067","article-title":"Metabolic and epigenetic action mechanisms of antidiabetic medicinal Plants","volume":"2019","author":"Shanak","year":"2019","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1113\/jphysiol.2003.049247","article-title":"Simple-sugar meals target GLUT2 at enterocyte apical membranes to improve sugar absorption: A study in GLUT2-null mice","volume":"552","author":"Gouyon","year":"2003","journal-title":"J. Physiol."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/11\/12\/1671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:25:18Z","timestamp":1760138718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/11\/12\/1671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["foods11121671"],"URL":"https:\/\/doi.org\/10.3390\/foods11121671","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,7]]}}}