{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:41:18Z","timestamp":1790361678796,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"publisher","award":["BIAF_RILO_17_01"],"award-info":[{"award-number":["BIAF_RILO_17_01"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"Universit\u00e0 degli Studi di Torino","doi-asserted-by":"publisher","award":["BIAF_RILO_18_01"],"award-info":[{"award-number":["BIAF_RILO_18_01"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["BIAF_FFABR_17_01"],"award-info":[{"award-number":["BIAF_FFABR_17_01"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011264","name":"FP7 People: Marie-Curie Actions","doi-asserted-by":"publisher","award":["609402-2020"],"award-info":[{"award-number":["609402-2020"]}],"id":[{"id":"10.13039\/100011264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["IJCI-2017-31665"],"award-info":[{"award-number":["IJCI-2017-31665"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Cocoa bean shell (CBS), a main byproduct of cocoa processing, represents a source of components such as polyphenols and methylxanthines, which have been associated with a reduced risk of several diseases. Therefore, CBS has potential application as a food ingredient. Intestinal mucosa is exposed to immune and inflammatory responses triggered by dietary agents, such as oxysterols, which derive from cholesterol oxidation and are pro-oxidant compounds able to affect intestinal function. We aimed at investigating the capability of the Forastero cultivar CBS, added or not added to ice cream, to protect against the intestinal barrier damage induced by a dietary oxysterol mixture. Methods: Composition and antioxidant capacity of in vitro digested CBS and CBS-enriched ice cream were analyzed by high-performance liquid chromatography and 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging assay, respectively. CaCo-2 cells differentiated into enterocyte-like monolayer were incubated with 60 \u00b5M oxysterol mixture in the presence of CBS formulations. Results: The oxysterol mixture induced tight junction impairment, interleukin-8 and monocyte chemoattractant protein-1 cell release, and oxidative stress-related nuclear factor erythroid 2 p45-related factor 2 response Nrf2. Both CBSs protected cells from these adverse effects, probably thanks to their high phenolic content. CBS-enriched ice cream showed the highest antioxidant capacity. Theobromine, which is in high concentrations of CBS, was also tested. Although theobromine exerted no effect on Nrf2 expression, its anti-inflammatory cooperating activity in CBS effect cannot be excluded. Conclusions: Our findings suggest that CBS-enriched ice cream may be effective in the prevention of gut integrity damage associated with oxidative\/inflammatory reactions.<\/jats:p>","DOI":"10.3390\/antiox10020280","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T18:45:00Z","timestamp":1613155500000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Protective Effect of Cocoa Bean Shell against Intestinal Damage: An Example of Byproduct Valorization"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5741-5774","authenticated-orcid":false,"given":"Daniela","family":"Rossin","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7158-6980","authenticated-orcid":false,"given":"Letricia","family":"Barbosa-Pereira","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Nutrition and Food Science, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-1525","authenticated-orcid":false,"given":"Noemi","family":"Iaia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sottero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice Costanza","family":"Danzero","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Poli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0397-6880","authenticated-orcid":false,"given":"Giuseppe","family":"Zeppa","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Forestry, and Food Sciences (DISAFA), University of Turin, 10095 Grugliasco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-3233","authenticated-orcid":false,"given":"Fiorella","family":"Biasi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.wasman.2019.04.030","article-title":"Biotechnological approaches for cocoa waste management: A review","volume":"90","author":"Pereira","year":"2019","journal-title":"Waste Manag."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"852","DOI":"10.2741\/4620","article-title":"Impact of chocolate on the cardiovascular health","volume":"23","author":"Gammone","year":"2018","journal-title":"Front. Biosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jad.2006.02.007","article-title":"Mood state effects of chocolate","volume":"92","author":"Parker","year":"2006","journal-title":"J. Affect. Disord."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Goya, L., Mart\u00edn, M.\u00c1., Sarri\u00e1, B., Ramos, S., Mateos, R., and Bravo, L. (2016). Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans. Nutrients, 8.","DOI":"10.3390\/nu8040212"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/FJC.0b013e3181b76787","article-title":"Cocoa, chocolate, and cardiovascular disease","volume":"54","author":"Galleano","year":"2009","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408398.2012.657921","article-title":"Cocoa and Human Health: From Head to Foot\u2014A Review","volume":"56","author":"Gattward","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Magrone, T., Russo, M.A., and Jirillo, E. (2017). Cocoa and Dark Chocolate Polyphenols: From Biology to Clinical Applications. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00677"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.tifs.2017.03.007","article-title":"Cocoa shell and its compounds: Applications in the food industry","volume":"63","author":"Okiyama","year":"2017","journal-title":"Trends Food Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Di Mattia, C.D., Sacchetti, G., Mastrocola, D., and Serafini, M. (2017). From Cocoa to Chocolate: The Impact of Processing on in vitro Antioxidant Activity and the Effects of Chocolate on Antioxidant Markers in vivo. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01207"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0308-8146(02)00385-0","article-title":"Dietary fibre in cocoa shell: Characterisation of component polysaccharides","volume":"81","author":"Redgwell","year":"2003","journal-title":"Food. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.foodres.2018.07.017","article-title":"The effect on bioactive components and characteristics of chocolate by functionalization with raw cocoa beans","volume":"113","author":"Budryn","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Panak Balenti\u0107, J., A\u010dkar, \u0110., Joki\u0107, S., Jozinovi\u0107, A., Babi\u0107, J., Mili\u010devi\u0107, B., \u0160ubari\u0107, D., and Pavlovi\u0107, N. (2018). Cocoa Shell: A By-Product with Great Potential for Wide Application. Molecules, 23.","DOI":"10.3390\/molecules23061404"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"526","DOI":"10.5582\/bst.2018.01172","article-title":"The beneficial and deleterious role of dietary polyphenols on chronic degenerative diseases by regulating gene expression","volume":"12","author":"Qu","year":"2019","journal-title":"Biosci. Trends."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kaulmann, A., and Bohn, T. (2016). Bioactivity of Polyphenols: Preventive and Adjuvant Strategies Toward Reducing Inflammatory Bowel Diseases-Promises, Perspectives, and Pitfalls. Oxid. Med. Cell Longev., 2016.","DOI":"10.1155\/2016\/9346470"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brglez Mojzer, E., Knez Hrn\u010di\u010d, M., \u0160kerget, M., Knez, \u017d., and Bren, U. (2016). Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects. Molecules, 21.","DOI":"10.3390\/molecules21070901"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Pinilla, E., O\u00f1atibia-Astibia, A., and Franco, R. (2015). The relevance of theobromine for the beneficial effects of cocoa consumption. Front. Pharmacol., 6.","DOI":"10.3389\/fphar.2015.00030"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Monteiro, J.P., Alves, M.G., Oliveira, P.F., and Silva, B.M. (2016). Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks. Molecules, 21.","DOI":"10.3390\/molecules21080974"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1021\/acs.jafc.9b02283","article-title":"Polyphenols and Intestinal Permeability: Rationale and Future Perspectives","volume":"68","author":"Bernardi","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Iaia, N., Rossin, D., Sottero, B., Venezia, I., Poli, G., and Biasi, F. (2020). Efficacy of theobromine in preventing intestinal CaCo-2 cell damage induced by oxysterols. Arch. Biochem. Biophys., 694.","DOI":"10.1016\/j.abb.2020.108591"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chelakkot, C., Ghim, J., and Ryu, S.H. (2018). Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp. Mol. Med., 50.","DOI":"10.1038\/s12276-018-0126-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1007\/s10620-006-9622-2","article-title":"Oxidative stress and pathogenesis of inflammatory bowel disease: An epiphenomenon or the cause?","volume":"52","author":"Rezaie","year":"2007","journal-title":"Dig. Dis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.freeradbiomed.2017.10.390","article-title":"Derangement of intestinal epithelial cell monolayer by dietary cholesterol oxidation products","volume":"113","author":"Deiana","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Molendijk, I., van der Marel, S., and Maljaars, P.W.J. (2019). Towards a Food Pharmacy: Immunologic Modulation through Diet. Nutrients, 11.","DOI":"10.3390\/nu11061239"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Leech, B., McIntyre, E., Steel, A., and Sibbritt, D. (2019). Risk factors associated with intestinal permeability in an adult population: A systematic review. Int. J. Clin. Pract., 73.","DOI":"10.1111\/ijcp.13385"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/advances\/nmz061","article-title":"Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review","volume":"11","author":"Rohr","year":"2020","journal-title":"Adv. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.fct.2010.09.023","article-title":"Oxysterols: A world to explore","volume":"48","author":"Ansorena","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1039\/C4FO01116C","article-title":"The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: Modulation by wine phenolics","volume":"6","author":"Guina","year":"2015","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1159\/000430366","article-title":"Contribution of Nrf2 to Atherogenic Phenotype Switching of Coronary Arterial Smooth Muscle Cells Lacking CD38 Gene","volume":"37","author":"Xu","year":"2015","journal-title":"Cell Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a Transcription Factor for Stress Response and Beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Rossin, D., Barbosa-Pereira, L., Iaia, N., Testa, G., Sottero, B., Poli, G., Zeppa, G., and Biasi, F. (2019). A Dietary Mixture of Oxysterols Induces in vitro Intestinal Inflammation through TLR2\/4 Activation: The Protective Effect of Cocoa Bean Shells. Antioxidants, 8.","DOI":"10.3390\/antiox8060151"},{"key":"ref_31","unstructured":"Barbosa-Pereira, L., Borotto Dalla Vecchia, S., Dal Bello, B., Bertolino, M., Belviso, S., Ghirardello, D., Berrino, P., and Zeppa, G. (2017, January 25\u201328). Cocoa bean shell as food ingredient to enhance the functional properties and nutritional quality of ice cream. Proceedings of the Fourth International Congress on Cocoa, Coffee and Tea, Turin, Italy."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1039\/C3FO60702J","article-title":"A standardised static in vitro digestion method suitable for food\u2014An international consensus","volume":"5","author":"Minekus","year":"2014","journal-title":"Food Funct."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rojo-Poveda, O., Barbosa-Pereira, L., El Khattabi, C., Youl, E.N., Bertolino, M., Delporte, C., Pochet, S., and St\u00e9vigny, C. (2020). Polyphenolic and Methylxanthine Bioaccessibility of Cocoa Bean Shell Functional Biscuits: Metabolomics Approach and Intestinal Permeability through Caco-2 Cell Models. Antioxidants, 9.","DOI":"10.3390\/antiox9111164"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/S0300-9084(86)80177-8","article-title":"The human colon carcinoma cell lines HT-29 and Caco-2: Two in vitro models for the study of intestinal differentiation","volume":"68","author":"Rousset","year":"1986","journal-title":"Biochimie"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Verhoeckx, K., Cotter, P., Lopez-Exposito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., and Wichers, H. (2015). CaCo-2 Cell Line. The Impact of Food Bioactives on Gut Health: In Vitro and Ex Vivo Models, Springer. [1st ed.].","DOI":"10.1007\/978-3-319-16104-4"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/0016-5085(90)90334-W","article-title":"Biosynthesis of alkaline phosphatase during differentiation of the human colon cancer cell line CaCo-2","volume":"98","author":"Matsumoto","year":"1990","journal-title":"Gastroenterology"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","unstructured":"Rio, D.C., Ares, M., Hannon, G.J., and Nilsen, T.W. (2010). Purification of RNA using TRIzol (TRI reagent). Cold Spring Harbor Protoc.","DOI":"10.1101\/pdb.prot5439"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hausmann, M. (2010). How bacteria-induced apoptosis of intestinal epithelial cells contributes to mucosal inflammation. Int. J. Inflam., 6.","DOI":"10.4061\/2010\/574568"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky gut: Mechanisms, measurement, and clinical implications in humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"GUT"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1194\/jlr.M500272-JLR200","article-title":"Plant sterols and stanols: Effects on mixed micellar composition and LXR (target gene) activation","volume":"46","author":"Plat","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"C909","DOI":"10.1111\/j.1750-3841.2011.02274.x","article-title":"Lipid and cholesterol oxidation in chicken meat are inhibited by sage but not by garlic","volume":"76","author":"Mariutti","year":"2011","journal-title":"J. Food Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Khan, M.I., Min, J.S., Lee, S.O., Yim, D.G., Seol, K.H., Lee, M., and Jo, C. (2015). Cooking, storage, and reheating effect on the formation of cholesterol oxidation products in processed meat products. Lipids Health Dis., 14.","DOI":"10.1186\/s12944-015-0091-5"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.fct.2014.04.005","article-title":"The effect of oxidized cholesterol on barrier functions and IL-10 mRNA expression in human intestinal epithelium co-cultured with dendritic cells in the transwell system","volume":"69","author":"Chalubinski","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.bbrc.2018.02.064","article-title":"7-Oxygenated cholesterol molecules differentially affect the expression of zonula occludens-1 in vascular smooth muscle cells and monocyte\/macrophage cells","volume":"497","author":"Cho","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.steroids.2015.02.004","article-title":"Oxysterols: Influence on plasma membrane rafts microdomains and development of ocular diseases","volume":"99","author":"Filomenko","year":"2015","journal-title":"Steroids"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Andrews, C., McLean, M.H., and Durum, S.K. (2018). Cytokine Tuning of Intestinal Epithelial Function. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01270"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00281-014-0421-0","article-title":"JAM-related proteins in mucosal homeostasis and inflammation","volume":"36","author":"Luissint","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1128\/MCB.06678-11","article-title":"Relocalization of junctional adhesion molecule A during inflammatory stimulation of brain endothelial cells","volume":"32","author":"Stamatovic","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.abb.2015.01.024","article-title":"(-)-Epicatechin in the prevention of tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity","volume":"573","author":"Contreras","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.redox.2017.11.002","article-title":"(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance","volume":"14","author":"Cremonini","year":"2018","journal-title":"Redox Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jnutbio.2017.07.015","article-title":"Monomeric cocoa catechins enhance \u03b2-cell function by increasing mitochondrial respiration","volume":"49","author":"Rowley","year":"2017","journal-title":"J. Nutr. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.mam.2018.01.007","article-title":"Plant bioactives and redox signaling: (-)-Epicatechin as a paradigm","volume":"61","author":"Fraga","year":"2018","journal-title":"Mol. Aspects Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.foodchem.2005.10.007","article-title":"Determination of theobromine, theophylline and caffeine in cocoa samples by a high-performance liquid chromatographic method with on-line sample cleanup in a switching-column system","volume":"100","author":"Brunetto","year":"2007","journal-title":"Food Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s00213-019-5172-0","article-title":"Exploring cocoa properties: Is theobromine a cognitive modulator?","volume":"236","author":"Cova","year":"2019","journal-title":"Psychopharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Jang, M.H., Mukherjee, S., Choi, M.J., Kang, N.H., Pham, H.G., and Yun, J.W. (2020). Theobromine alleviates diet-induced obesity in mice via phosphodiesterase-4 inhibition. Eur. J. Nutr.","DOI":"10.1007\/s00394-020-02184-6"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Gu, R., Shi, Y., Huang, W., Lao, C., Zou, Z., Pan, S., and Huang, Z. (2020). Theobromine mitigates IL-1\u03b2-induced oxidative stress, inflammatory response, and degradation of type II collagen in human chondrocytes. Int. Immunopharmacol., 5.","DOI":"10.1016\/j.intimp.2020.106226"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/2\/280\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:23:15Z","timestamp":1760160195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/2\/280"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,12]]},"references-count":59,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["antiox10020280"],"URL":"https:\/\/doi.org\/10.3390\/antiox10020280","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,12]]}}}