{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:13:52Z","timestamp":1785428032448,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n, Spain","doi-asserted-by":"crossref","award":["RTI2018-097549-B-I00"],"award-info":[{"award-number":["RTI2018-097549-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RTI2018-097549-B-I00"],"award-info":[{"award-number":["RTI2018-097549-B-I00"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003339","name":"Consejo Superior de Investigaciones Cient\u00edficas","doi-asserted-by":"publisher","award":["New insights to support health claims and consumer acceptance of sustainable foods\u201d (202470E207, CSIC)"],"award-info":[{"award-number":["New insights to support health claims and consumer acceptance of sustainable foods\u201d (202470E207, CSIC)"]}],"id":[{"id":"10.13039\/501100003339","id-type":"DOI","asserted-by":"publisher"}]},{"award":["New insights to support health claims and consumer acceptance of sustainable foods\u201d (202470E207, CSIC)"],"award-info":[{"award-number":["New insights to support health claims and consumer acceptance of sustainable foods\u201d (202470E207, CSIC)"]}],"id":[{"id":"https:\/\/ror.org\/02gfc7t72","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Instant Cascara (IC) beverages, derived from dried coffee cherry pulp, represent an upcycled plant-based ingredient rich in phenolic compounds and methylxanthines. Although spray-drying enables the production of soluble cascara powders without carriers, previous sensory evaluation highlighted limitations in palatability, supporting the need for formulation strategies. Objective: To evaluate how the incorporation of inulin-type carriers with different degrees of polymerization modulates production yield, the apparent recovery of bioactive compounds, and formulation-dependent in vitro biological and receptor-level responses of Instant Cascara beverages. Methods: Formulations without carrier (IC 0.0) and with long-chain inulin (IC 1.0) or oligofructose-enriched inulin (IC 2.0) were prepared and characterized. Production yield, phytochemical composition, and in vitro antioxidant, anti-inflammatory, antiproliferative, and receptor-mediated responses were assessed using analytical tools, cell-based assays, and receptor-based platforms. Results: Carrier incorporation improved production yield, particularly for IC 1.0. Although differences in apparent recovery of bioactive compounds were observed, all formulations preserved relevant in vitro biological activities. IC 2.0 showed stronger nitric oxide inhibition and apoptosis induction in colorectal cancer cell models. Receptor-based assays revealed formulation-dependent differences, including reduced activation of bitter taste receptors (TAS2Rs), absence of sweet receptor (TAS1R2\/TAS1R3) activation, and modulation of muscarinic (M3) and dopaminergic (D3\/D4) receptor responses. These effects are consistent with variations in the composition and effective concentration of bioactive compounds between formulations, particularly caffeine. Conclusions: The incorporation of inulin-type carriers influences production yield and modulates in vitro biological responses and receptor-level responses of Instant Cascara beverages. IC 2.0 represents a formulation with a favorable balance between technological performance and functional responses, associated with a distinct receptor-level profile. This balance may be related to a reduced contribution of bitterness-associated compounds, such as caffeine, together with the preservation of other bioactive components contributing to the observed biological responses. These findings provide a mechanistic in vitro basis for future sensory and in vivo studies evaluating how formulation-dependent differences in bioactive composition may influence physiological responses and consumer perception.<\/jats:p>","DOI":"10.3390\/nu18121932","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:00:48Z","timestamp":1781535648000},"page":"1932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Instant Cascara Beverages with Inulin-Type Carriers: Production Yield, In Vitro Biological Activity and Receptor-Level Responses"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5828-2587","authenticated-orcid":false,"given":"Vanesa","family":"S\u00e1nchez-Mart\u00edn","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias de la Alimentaci\u00f3n (CIAL), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid (UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta B.","family":"L\u00f3pez-Parra","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias de la Alimentaci\u00f3n (CIAL), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid (UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6556-1867","authenticated-orcid":false,"given":"Margriet","family":"Roelse","sequence":"additional","affiliation":[{"name":"Business Unit Bioscience, Wageningen Plant Research, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3246-7919","authenticated-orcid":false,"given":"Amaia","family":"Iriondo-DeHond","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Departamental de Nutrici\u00f3n y Ciencia de los Alimentos, Departamento de Nutrici\u00f3n y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3606-9507","authenticated-orcid":false,"given":"Paloma","family":"Morales","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Departamental de Nutrici\u00f3n y Ciencia de los Alimentos, Departamento de Nutrici\u00f3n y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-1113","authenticated-orcid":false,"given":"Ana I.","family":"Haza","sequence":"additional","affiliation":[{"name":"Secci\u00f3n Departamental de Nutrici\u00f3n y Ciencia de los Alimentos, Departamento de Nutrici\u00f3n y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5799-2301","authenticated-orcid":false,"given":"Maarten A.","family":"Jongsma","sequence":"additional","affiliation":[{"name":"Business Unit Bioscience, Wageningen Plant Research, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6309-5383","authenticated-orcid":false,"given":"Mar\u00eda Dolores del","family":"Castillo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias de la Alimentaci\u00f3n (CIAL), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Universidad Aut\u00f3noma de Madrid (UAM), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","unstructured":"(2025, December 02). Commission Implementing Regulation (EU) 2022\/47 of 13 January 2022 Authorising the Placing on the Market of Coffea arabica L. and\/or Coffea Canephora Pierre Ex A. Froehner Dried Cherry Pulp and Its Infusion as a Traditional Food from a Third Country Under Regulation (EU) 2015\/2283 of the European Parliament and of the Council and Amending Commission Implementing Regulation (EU) 2017\/2470. Available online: http:\/\/data.europa.eu\/eli\/reg_impl\/2022\/47\/oj."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Parra, M.B., G\u00f3mez-Dom\u00ednguez, I., Iriondo-DeHond, M., Villamediana Merino, E., S\u00e1nchez-Mart\u00edn, V., Mendiola, J.A., Iriondo-DeHond, A., and del Castillo, M.D. (2024). The Impact of the Drying Process on the Antioxidant and Anti-Inflammatory Potential of Dried Ripe Coffee Cherry Pulp Soluble Powder. Foods, 13.","DOI":"10.3390\/foods13071114"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sales, A.L., Iriondo-DeHond, A., DePaula, J., Ribeiro, M., Ferreira, I.M.P.L.V.O., Miguel, M.A.L., del Castillo, M.D., and Farah, A. (2023). Intracellular Antioxidant and Anti-Inflammatory Effects and Bioactive Profiles of Coffee Cascara and Black Tea Kombucha Beverages. Foods, 12.","DOI":"10.3390\/foods12091905"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Mart\u00edn, V., L\u00f3pez-Parra, M.B., Iriondo-DeHond, A., Haza, A.I., Morales, P., and del Castillo, M.D. (2023). Instant Cascara: A Potential Sustainable Promoter of Gastrointestinal Health. Proceedings of the International Coffee Convention 2023, Mannheim, Germany, 30 September\u20133 October 2023, MDPI AG.","DOI":"10.3390\/ICC2023-14841"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gallego-Barcel\u00f3, P., Ben\u00edtez-\u00c1lvarez, D., Bagues, A., Silv\u00e1n-Ros, B., Montalb\u00e1n-Rodr\u00edguez, A., L\u00f3pez-G\u00f3mez, L., Vera, G., del Castillo, M.D., Uranga, J.A., and Abalo, R. (2024). Ex Vivo Study of Colon Health, Contractility and Innervation in Male and Female Rats after Regular Exposure to Instant Cascara Beverage. Foods, 13.","DOI":"10.3390\/foods13162474"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117539","DOI":"10.1016\/j.lwt.2025.117539","article-title":"A Novel Beverage of Coffee Cherry (Cascara) Water Kefir Rich in Antioxidants, Bioactive Compounds, and Exhibiting Promising Antibacterial and Sensory Qualities","volume":"219","author":"Chomphoosee","year":"2025","journal-title":"LWT"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gallego-Barcel\u00f3, P., L\u00f3pez-Tofi\u00f1o, Y., L\u00f3pez-G\u00f3mez, L., Vera, G., Bagues, A., Esteban-Hern\u00e1ndez, J., del Castillo, M.D., Uranga, J.A., and Abalo, R. (2025). Instant Cascara Beverage as a Neuroimmune Modulator of the Brain\u2013Gut Axis: Sex-Dependent Effects in Healthy Rats. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110691"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ueda, J.M., Morales, P., Fern\u00e1ndez-Ruiz, V., Ferreira, A., Barros, L., Carocho, M., and Heleno, S.A. (2023). Powdered Foods: Structure, Processing, and Challenges: A Review. Appl. Sci., 13.","DOI":"10.3390\/app132212496"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1007\/s00394-020-02282-5","article-title":"Prebiotic Effect of Inulin-Type Fructans on Faecal Microbiota and Short-Chain Fatty Acids in Type 2 Diabetes: A Randomised Controlled Trial","volume":"59","author":"Birkeland","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1093\/advances\/nmab119","article-title":"The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review","volume":"13","author":"Hughes","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Michalska-Ciechanowska, A., Brzezowska, J., del Castillo, M.D., L\u00f3pez-Parra, M.B., Montero, L., Nicolet, N., Turkiewicz, I.P., and Andlauer, W. (2025). Impact of Thermal Processing and Carbohydrate Carriers on Amino Acids, Sugars, Phenolic Compounds, and Maillard Reaction Markers Relevant to Nutritional Quality and Safety of Rosa canina L. Juice Powders. Molecules, 30.","DOI":"10.3390\/molecules30183805"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.1111\/ijfs.17562","article-title":"Innovative of Cascara as Potential in Beverage, Food and Their Functional Impact: A Review","volume":"59","author":"Wibowo","year":"2024","journal-title":"Int. J. Food Sci. Technol."},{"key":"ref_13","unstructured":"(2014). Scientific Opinion on the Substantiation of a Health Claim Related to Non Digestible Carbohydrates and a Reduction of Post Prandial Glycaemic Responses Pursuant to Article 13(5) of Regulation (EC) No 1924\/2006. EFSA J., 12, 3513."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Fern\u00e1ndez, A.M., Dellacassa, E., Nardin, T., Larcher, R., G\u00e1mbaro, A., Medrano-Fernandez, A., and Del Castillo, M.D. (2021). In Vitro Bioaccessibility of Bioactive Compounds from Citrus Pomaces and Orange Pomace Biscuits. Molecules, 26.","DOI":"10.3390\/molecules26123480"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.indcrop.2014.08.046","article-title":"Phenolic Composition, Antioxidant and Anti-Inflammatory Activities of Extracts from Moroccan Opuntia Ficus-Indica Flowers Obtained by Different Extraction Methods","volume":"62","author":"Benayad","year":"2014","journal-title":"Ind. Crops Prod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/0014-4827(92)90378-L","article-title":"Factors Influencing DNA Migration from Individual Cells Subjected to Gel Electrophoresis","volume":"198","author":"Olive","year":"1992","journal-title":"Exp. Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Mart\u00edn, V., Jim\u00e9nez-Garc\u00eda, L., Herranz, S., Luque, A., Acebo, P., Amesty, \u00c1., Est\u00e9vez-Braun, A., De Las Heras, B., and Hortelano, S. (2019). \u03b1-Hispanolol Induces Apoptosis and Suppresses Migration and Invasion of Glioblastoma Cells Likely via Downregulation of MMP-2\/9 Expression and P38MAPK Attenuation. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00935"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Mart\u00edn, V., Morales, P., Iriondo-DeHond, A., Hospital, X.F., Fern\u00e1ndez, M., Hierro, E., and Haza, A.I. (2023). Differential Apoptotic Effects of Bee Product Mixtures on Normal and Cancer Hepatic Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12030615"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15854","DOI":"10.1021\/acs.jafc.4c00815","article-title":"Tongue-on-a-Chip: Parallel Recording of Sweet and Bitter Receptor Responses to Sequential Injections of Pure and Mixed Sweeteners","volume":"72","author":"Roelse","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13268","DOI":"10.1038\/ncomms13268","article-title":"Coupling Optogenetic Stimulation with NanoLuc-Based Luminescence (BRET) Ca++ Sensing","volume":"7","author":"Yang","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.foodres.2017.12.050","article-title":"Effect of Dietary Fiber (Inulin) Addition on Phenolics and in Vitro Bioaccessibility of Tomato Sauce","volume":"106","author":"Tomas","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Leyva-Jim\u00e9nez, F.J., Lozano-S\u00e1nchez, J., de la Luz C\u00e1diz-Gurrea, M., Fern\u00e1ndez-Ochoa, \u00c1., Arr\u00e1ez-Rom\u00e1n, D., and Segura-Carretero, A. (2020). Spray-Drying Microencapsulation of Bioactive Compounds from Lemon Verbena Green Extract. Foods, 9.","DOI":"10.3390\/foods9111547"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Michalska, A., Wojdy\u0142o, A., Brzezowska, J., Majerska, J., and Ciska, E. (2019). The Influence of Inulin on the Retention of Polyphenolic Compounds during the Drying of Blackcurrant Juice. Molecules, 24.","DOI":"10.3390\/molecules24224167"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"\u0218tef\u0103nescu, B.E., Nemes, S.A., Teleky, B.E., C\u0103linoiu, L.F., Mitrea, L., Mart\u0103u, G.A., Szabo, K., Mihai, M., Vodnar, D.C., and Cri\u0219an, G. (2022). Microencapsulation and Bioaccessibility of Phenolic Compounds of Vaccinium Leaf Extracts. Antioxidants, 11.","DOI":"10.3390\/antiox11040674"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.31665\/JFB.2018.4162","article-title":"Bioaccessibility and Bioavailability of Phenolic Compounds","volume":"4","author":"Shahidi","year":"2018","journal-title":"J. Food Bioact."},{"key":"ref_26","first-page":"6175804","article-title":"ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells","volume":"2019","author":"Snezhkina","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_27","first-page":"350","article-title":"Reactive Oxygen Species and Colorectal Cancer","volume":"9","author":"Sreevalsan","year":"2013","journal-title":"Curr. Color. Cancer Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sorolla, M.A., Hidalgo, I., Sorolla, A., Montal, R., Pallis\u00e9, O., Salud, A., and Parisi, E. (2021). Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities. Cancers, 13.","DOI":"10.3390\/cancers13205037"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5119","DOI":"10.1002\/jcp.26356","article-title":"Reactive Oxygen Species and Colorectal Cancer","volume":"233","author":"Lin","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Castaldo, L., Toriello, M., Sessa, R., Izzo, L., Lombardi, S., Narv\u00e1ez, A., Ritieni, A., and Grosso, M. (2021). Antioxidant and Anti-Inflammatory Activity of Coffee Brew Evaluated after Simulated Gastrointestinal Digestion. Nutrients, 13.","DOI":"10.3390\/nu13124368"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.foodchem.2016.09.159","article-title":"Evaluation of the Antioxidant Capacity, Furan Compounds and Cytoprotective\/Cytotoxic Effects upon Caco-2 Cells of Commercial Colombian Coffee","volume":"219","author":"Cilla","year":"2017","journal-title":"Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Condello, M., and Meschini, S. (2021). Role of Natural Antioxidant Products in Colorectal Cancer Disease: A Focus on a Natural Compound Derived from Prunus Spinosa, Trigno Ecotype. Cells, 10.","DOI":"10.3390\/cells10123326"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/s41598-023-50947-y","article-title":"Mangiferin (Mango) Attenuates AOM-Induced Colorectal Cancer in Rat\u2019s Colon by Augmentation of Apoptotic Proteins and Antioxidant Mechanisms","volume":"14","author":"Jabbar","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1080\/10942912.2019.1593193","article-title":"Chemopreventive Effect of Coffee against Colorectal Cancer and Hepatocellular Carcinoma","volume":"22","author":"Arroyave","year":"2019","journal-title":"Int. J. Food Prop."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Guarino, M.P.L., Altomare, A., Emerenziani, S., Di Rosa, C., Ribolsi, M., Balestrieri, P., Iovino, P., Rocchi, G., and Cicala, M. (2020). Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults. Nutrients, 12.","DOI":"10.3390\/nu12041037"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic Inflammation in the Etiology of Disease across the Life Span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, M.E., and Lee, J.S. (2025). Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031204"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e23765","DOI":"10.1002\/jbt.23765","article-title":"Mangiferin: A Natural Bioactive Immunomodulating Glucosylxanthone with Potential against Cancer and Rheumatoid Arthritis","volume":"38","author":"Akkewar","year":"2024","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kupczyk, D., Bilski, R., Szeleszczuk, \u0141., M\u0105dra-Gackowska, K., and Studzi\u0144ska, R. (2025). The Role of Diet in Modulating Inflammation and Oxidative Stress in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis. Nutrients, 17.","DOI":"10.3390\/nu17091603"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.mrgentox.2018.01.010","article-title":"Assessment of the Predictive Capacity of the Optimized in Vitro Comet Assay Using HepG2 Cells","volume":"827","author":"Hong","year":"2018","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/em.22157","article-title":"Genotoxicity of 11 Heavy Metals Detected as Food Contaminants in Two Human Cell Lines","volume":"59","author":"Kopp","year":"2018","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bukowska, B., Mokra, K., and Micha\u0142owicz, J. (2022). Benzo[a]Pyrene\u2014Environmental Occurrence, Human Exposure, and Mechanisms of Toxicity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116348"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s00204-001-0295-5","article-title":"The Coffee Components Kahweol and Cafestol Induce \u03b3-Glutamylcysteine Synthetase, the Rate Limiting Enzyme of Chemoprotective Glutathione Synthesis, in Several Organs of the Rat","volume":"75","author":"Huber","year":"2002","journal-title":"Arch. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.foodres.2017.08.012","article-title":"Validation of Coffee Silverskin Extract as a Food Ingredient by the Analysis of Cytotoxicity and Genotoxicity","volume":"100","author":"Haza","year":"2017","journal-title":"Food Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/1541-7786.MCR-23-0411","article-title":"Updating the Definition of Cancer","volume":"21","author":"Brown","year":"2023","journal-title":"Mol. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"193","DOI":"10.18632\/oncotarget.28382","article-title":"V Selective Protection of Normal Cells from Chemotherapy, While Killing Drug-Resistant Cancer Cells","volume":"14","author":"Blagosklonny","year":"2023","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.fct.2016.07.008","article-title":"The Coffee Diterpene Kahweol Suppresses the Cell Proliferation by Inducing Cyclin D1 Proteasomal Degradation via ERK1\/2, JNK and GKS3\u03b2-Dependent Threonine-286 Phosphorylation in Human Colorectal Cancer Cells","volume":"95","author":"Park","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bu\u0142dak, R.J., Hejmo, T., Osowski, M., Bu\u0142dak, \u0141., Kukla, M., Polaniak, R., and Birkner, E. (2018). The Impact of Coffee and Its Selected Bioactive Compounds on the Development and Progression of Colorectal Cancer in Vivo and in Vitro. Molecules, 23.","DOI":"10.3390\/molecules23123309"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"154854","DOI":"10.1016\/j.prp.2023.154854","article-title":"The Pathophysiology of the Cell Cycle in Cancer and Treatment Strategies Using Various Cell Cycle Checkpoint Inhibitors","volume":"251","author":"Almalki","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kluska, M., and Wo\u017aniak, K. (2021). Natural Polyphenols as Modulators of Etoposide Anti-Cancer Activity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126602"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ekbatan, S.S., Li, X.Q., Ghorbani, M., Azadi, B., and Kubow, S. (2018). Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030723"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Cano-Mu\u00f1oz, P., Rebollo-Hernanz, M., Braojos, C., Ca\u00f1as, S., Gil-Ramirez, A., Aguilera, Y., Martin-Cabrejas, M.A., and Benitez, V. (2022). Comparative Investigation on Coffee Cascara from Dry and Wet Methods: Chemical and Functional Properties, MDPI AG.","DOI":"10.3390\/Foods2021-10975"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Babaei Rad, S., Mumivand, H., Mollaei, S., and Khadivi, A. (2025). Effect of Drying Methods on Phenolic Compounds and Antioxidant Activity of Capparis spinosa L. Fruits. BMC Plant Biol., 25.","DOI":"10.1186\/s12870-025-06110-y"},{"key":"ref_54","first-page":"1145960","article-title":"Modulation of Bitter Taste Receptors by Yeast Extracts","volume":"19","author":"Belloir","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"129225","DOI":"10.1016\/j.foodchem.2021.129225","article-title":"Identification of Coffee Compounds That Suppress Bitterness of Brew","volume":"350","author":"Gao","year":"2021","journal-title":"Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1080\/10408398.2024.2326012","article-title":"A Review on Natural Sweeteners, Sweet Taste Modulators and Bitter Masking Compounds: Structure-Activity Strategies for the Discovery of Novel Taste Molecules","volume":"65","author":"An","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Bhai, S., Bhowmick, P., Bhowmik, R., and Bhowmick, M. (2026). Inulin in Nutraceuticals and Sensory Aspects of Inulin in Food. Comprehensive Guide to Inulin, Elsevier.","DOI":"10.1016\/B978-0-443-36617-8.00004-6"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s43014-025-00322-3","article-title":"Polyphenol-Polysaccharide Interactions: Molecular Mechanisms and Potential Applications in Food Systems\u2014A Comprehensive Review","volume":"7","author":"Shahidi","year":"2025","journal-title":"Food Prod. Process. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, X., Yu, Y., Zhang, H., Zhang, M., and Liu, Y. (2024). The Role of Muscarinic Acetylcholine Receptor M3 in Cardiovascular Diseases. Int. J. Mol. Sci., 25.","DOI":"10.22541\/au.171008718.80347563\/v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jff.2019.02.018","article-title":"Rooibos (Aspalathus linearis) Extract, Containing Eriodictyol-6-C-\u03b2-D-Glucoside as the Active Component, Stimulates Exocrine Glands via the M 3 Muscarinic Acetylcholine Receptor","volume":"55","author":"Nishimachi","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/mnfr.201100453","article-title":"Multi-Parametric Approach to Identify Coffee Components That Regulate Mechanisms of Gastric Acid Secretion","volume":"56","author":"Rubach","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_62","unstructured":"Bhatia, A., Lenchner, J.R., and Saadabadi, A. (2023). Biochemistry, Dopamine Receptors, StatPearls (StatPearls Publishing)."},{"key":"ref_63","first-page":"38","article-title":"Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain\u2013Gut Axis","volume":"13","author":"Uranga","year":"2021","journal-title":"Nutrients"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/12\/1932\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:13:47Z","timestamp":1782533627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/12\/1932"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,15]]},"references-count":63,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["nu18121932"],"URL":"https:\/\/doi.org\/10.3390\/nu18121932","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,15]]}}}