{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:20:27Z","timestamp":1784694027177,"version":"3.55.0"},"reference-count":125,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This review aims to comprehensively examine spent coffee grounds (SCGs) as a sustainable source of antioxidant and immunomodulatory bioactives, with a specific focus on their capacity to modulate membrane-level signaling through ion channels and G-protein-coupled receptors (GPCRs) in the context of lifestyle-related chronic diseases. SCGs, the major solid by-product of coffee brewing, represent an underutilized yet highly abundant source of bioactive compounds, including chlorogenic acids, phenolic acids, melanoidins, diterpenes, and residual alkaloids. Lifestyle-related chronic diseases, including type 2 diabetes, obesity, cardiovascular disease, and chronic inflammatory disorders, are increasingly recognized as immunometabolic conditions driven by persistent low-grade inflammation, redox imbalance, and dysregulated membrane signaling. This review synthesizes current evidence demonstrating that bioactives contained in SCG extracts exert antioxidant and immunomodulatory effects that extend beyond radical scavenging. Crucially, these compounds also act as modulators of membrane-level signaling, representing a mechanistic perspective that has not been previously integrated for SCGs in the context of chronic disease. The different extraction methodologies and the obtained results are evaluated with the aim to identify the most effective experimental approach and extraction conditions. The paper also discusses how SCG compounds regulate redox-sensitive ion channels (including calcium channels, TRP channels, and potassium channels), and key GPCR pathways (such as GPR120, GPR43, and adenosine receptors), thereby influencing immune cell activation, cytokine production, insulin signaling, and metabolic inflammation. Particular attention is given to the role of microbial fermentation and enzymatic processing in enhancing SCG bioavailability, generating postbiotic metabolites that further engage GPCR\u2013ion channel crosstalk. By integrating extraction approaches, antioxidant chemistry, immunology, membrane signaling, and nutritional metabolism, this review positions SCG as a sustainable functional ingredient capable of restoring immune tolerance and metabolic homeostasis. These insights support the valorization of SCGs within the circular economy framework and highlight their potential application in next-generation immunonutrition strategies for chronic disease prevention and management.<\/jats:p>","DOI":"10.3390\/ijms27114980","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spent Coffee Ground Extracts: A Sustainable Source of Antioxidant and Immunomodulatory Bioactives for Managing Lifestyle-Related Chronic Diseases"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6422-1492","authenticated-orcid":false,"given":"Alifah","family":"Hasna","sequence":"first","affiliation":[{"name":"Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia"},{"name":"School of Medicine, Faculty of Medicine, Universitas 17 Agustus 1945 (UNTAG) Surabaya, Surabaya 60118, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda Anasthasya","family":"Tansy","sequence":"additional","affiliation":[{"name":"Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia"},{"name":"School of Medicine, Faculty of Medicine, Universitas 17 Agustus 1945 (UNTAG) Surabaya, Surabaya 60118, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5221-7648","authenticated-orcid":false,"given":"Armansyah Maulana","family":"Harahap","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Health and Recreation, Faculty of Sport, Universitas Negeri Medan, Medan 20221, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maulana Bagus Adi","family":"Cahyono","sequence":"additional","affiliation":[{"name":"Medical Program, Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0544-2807","authenticated-orcid":false,"given":"Edwin","family":"Hadinata","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medicine, Ciputra University of Surabaya, Surabaya 60219, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Rubianto","family":"Tjandrawinata","sequence":"additional","affiliation":[{"name":"School of Bioscience, Innovation and Technology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-0854","authenticated-orcid":false,"given":"Fahrul","family":"Nurkolis","sequence":"additional","affiliation":[{"name":"Master of Basic Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia"},{"name":"Medical Research Center of Indonesia, Surabaya 60281, Indonesia"},{"name":"Institute for Research and Community Service, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2287-3633","authenticated-orcid":false,"given":"Lucia De","family":"Luca","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Napoli Federico II, Piazza Carlo di Borbone 1, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5070-0860","authenticated-orcid":false,"given":"Giulia","family":"Basile","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Napoli Federico II, Piazza Carlo di Borbone 1, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7555-0486","authenticated-orcid":false,"given":"Raffaele","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Agricultural Sciences, University of Napoli Federico II, Piazza Carlo di Borbone 1, 80055 Portici, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-3327","authenticated-orcid":false,"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano, 49, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Deck, K., Mora, C., Deng, S., Rogers, P., Rafferty, T., Palade, P.T., Mu, S., Liu, Y., Deck, K., and Mora, C. (2025). Immune Dysregulation Connecting Type 2 Diabetes and Cardiovascular Complications. Life, 15.","DOI":"10.3390\/life15081241"},{"key":"ref_2","first-page":"e94863","article-title":"Addressing Meta-Inflammation in the Comprehensive Management of Chronic Pain","volume":"17","author":"McMasters","year":"2025","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bellanti, F., Coda, A.R.D., Trecca, M.I., Lo Buglio, A., Serviddio, G., and Vendemiale, G. (2025). Redox Imbalance in Inflammation: The Interplay of Oxidative and Reductive Stress. Antioxidants, 14.","DOI":"10.3390\/antiox14060656"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Leyane, T.S., Jere, S.W., Houreld, N.N., Leyane, T.S., Jere, S.W., and Houreld, N.N. (2022). Oxidative Stress in Ageing and Chronic Degenerative Pathologies: Molecular Mechanisms Involved in Counteracting Oxidative Stress and Chronic Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137273"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41392-025-02253-4","article-title":"Mitochondria in Oxidative Stress, Inflammation and Aging: From Mechanisms to Therapeutic Advances","volume":"10","author":"Xu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"107579","DOI":"10.1016\/j.phrs.2025.107579","article-title":"Targeting Ion Homeostasis in Metabolic Diseases: Molecular Mechanisms and Targeted Therapies","volume":"212","author":"Zhang","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jaci.2020.08.013","article-title":"Regulating Metabolic Inflammation by Nutritional Modulation","volume":"146","author":"Mitchelson","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, Metaflammation and Immunometabolic Disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Stokes, L., MacKenzie, A.B., and Sluyter, R. (2016). Editorial: Roles of Ion Channels in Immune Cells. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00048"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Manolios, N., Papaemmanouil, J., and Adams, D.J. (2023). The Role of Ion Channels in T Cell Function and Disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1238171"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s12929-017-0375-3","article-title":"Role of Mitochondrial Dysfunction and Dysregulation of Ca2+ Homeostasis in the Pathophysiology of Insulin Resistance and Type 2 Diabetes","volume":"24","author":"Wang","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Franca, A.S., and Oliveira, L.S. (2022). Potential Uses of Spent Coffee Grounds in the Food Industry. Foods, 11.","DOI":"10.3390\/foods11142064"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"108534","DOI":"10.1016\/j.biombioe.2025.108534","article-title":"Multivalorization of Spent Coffee Grounds Towards a Waste Free Solution","volume":"205","author":"Eiseman","year":"2026","journal-title":"Biomass Bioenergy"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Balushi, J.A., Saadi, S.A., Ahanchi, M., Attar, M.A., Jafary, T., Hinai, M.A., Yeneneh, A.M., Basha, J.S., Balushi, J.A., and Saadi, S.A. (2025). A Comprehensive Review on Sustainable Conversion of Spent Coffee Grounds into Energy Resources and Environmental Applications. Biomass, 5.","DOI":"10.3390\/biomass5030055"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Solomakou, N., Tsafrakidou, P., Goula, A.M., Solomakou, N., Tsafrakidou, P., and Goula, A.M. (2022). Valorization of SCG Through Extraction of Phenolic Compounds and Synthesis of New Biosorbent. Sustainability, 14.","DOI":"10.3390\/su14159358"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s11157-023-09669-w","article-title":"Spent Coffee Ground: Transformation from Environmental Burden into Valuable Bioactive Metabolites","volume":"22","author":"Singh","year":"2023","journal-title":"Rev. Environ. Sci. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Maier, B., Franke, H., Schwarz, S., Lachenmeier, D.W., Maier, B., Franke, H., Schwarz, S., and Lachenmeier, D.W. (2025). Toxicological Risk Assessment of Coffee Oil (Coffee Seed Oil and Spent Coffee Grounds Oil) as a Novel Food with Focus on Cafestol. Molecules, 30.","DOI":"10.3390\/molecules30142951"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1111\/1541-4337.12620","article-title":"Chlorogenic Acid: A Comprehensive Review of the Dietary Sources, Processing Effects, Bioavailability, Beneficial Properties, Mechanisms of Action, and Future Directions","volume":"19","author":"Lu","year":"2020","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1021\/acs.jafc.0c03804","article-title":"Current Advances in Naturally Occurring Caffeoylquinic Acids: Structure, Bioactivity, and Synthesis","volume":"68","author":"Liu","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.2174\/0929867329666220816154634","article-title":"Chlorogenic Acid: A Dietary Phenolic Acid with Promising Pharmacotherapeutic Potential","volume":"30","author":"Singh","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Iriondo-DeHond, A., Rodr\u00edguez Casas, A., and del Castillo, M.D. (2021). Interest of Coffee Melanoidins as Sustainable Healthier Food Ingredients. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.730343"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8954","DOI":"10.1080\/10408398.2021.1937509","article-title":"Dissecting Dietary Melanoidins: Formation Mechanisms, Gut Interactions and Functional Properties","volume":"62","author":"Shaheen","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Antonietti, S., Silva, A.M., Sim\u00f5es, C., Almeida, D., F\u00e9lix, L.M., Papetti, A., and Nunes, F.M. (2022). Chemical Composition and Potential Biological Activity of Melanoidins from Instant Soluble Coffee and Instant Soluble Barley: A Comparative Study. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.825584"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5846","DOI":"10.1080\/10408398.2024.2433610","article-title":"Unraveling the Mysteries of Melanoidins: Insights into Formation, Structure, and Health Potential in Fermented Blacken Foods","volume":"65","author":"Zhang","year":"2025","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16","DOI":"10.31069\/japsr.v6i3.04","article-title":"A Comprehensive Review on Pharmacological Potentials of Caffeine","volume":"6","author":"Sharma","year":"2023","journal-title":"J. Appl. Pharm. Sci. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1007\/s10571-021-01077-4","article-title":"Caffeine and Its Neuroprotective Role in Ischemic Events: A Mechanism Dependent on Adenosine Receptors","volume":"42","author":"Nascimento","year":"2022","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_27","unstructured":"Efthymiopoulos, I. (2018). Recovery of Lipids from Spent Coffee Grounds for Use as a Biofuel. [Ph.D. Thesis, UCL (University College London)]."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hao, W.-R., Cheng, C.-Y., Chen, H.-Y., Chen, J.-J., Cheng, T.-H., Liu, J.-C., Hao, W.-R., Cheng, C.-Y., Chen, H.-Y., and Chen, J.-J. (2024). The Association between Cafestol and Cardiovascular Diseases: A Comprehensive Review. Medicina, 60.","DOI":"10.20944\/preprints202405.0067.v1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejphar.2017.12.030","article-title":"Cafestol, a Coffee Diterpene, Inhibits Urotensin II-Induced Interleukin-8 Expression in Human Umbilical Vein Endothelial Cells","volume":"820","author":"Tsai","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Nguyen, V., Taine, E.G., Meng, D., Cui, T., and Tan, W. (2024). Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients, 16.","DOI":"10.3390\/nu16070924"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.clnu.2016.03.002","article-title":"Chlorogenic Acid Protects against Liver Fibrosis in Vivo and in Vitro through Inhibition of Oxidative Stress","volume":"35","author":"Shi","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_32","first-page":"75","article-title":"Extraction of Oligosaccharides and Phenolic Compounds by Roasting Pretreatment and Enzymatic Hydrolysis from Spent Coffee Ground","volume":"8","author":"Bhaturiwala","year":"2020","journal-title":"J. Appl. Biol. Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.canlet.2004.04.002","article-title":"The Coffee Diterpene Kahweol Suppress the Inducible Nitric Oxide Synthase Expression in Macrophages","volume":"213","author":"Kim","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ijbiomac.2020.01.281","article-title":"Procuring Biologically Active Galactomannans from Spent Coffee Ground (SCG) by Autohydrolysis and Enzymatic Hydrolysis","volume":"149","author":"Gu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luna, K.A., Aguilar, C.N., Ram\u00edrez-Guzm\u00e1n, N., Ruiz, H.A., Mart\u00ednez, J.L., Ch\u00e1vez-Gonz\u00e1lez, M.L., Luna, K.A., Aguilar, C.N., Ram\u00edrez-Guzm\u00e1n, N., and Ruiz, H.A. (2025). Bioprocessing of Spent Coffee Grounds as a Sustainable Alternative for the Production of Bioactive Compounds. Fermentation, 11.","DOI":"10.3390\/fermentation11070366"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115974","DOI":"10.1016\/j.lwt.2024.115974","article-title":"Exploitation of Spent Coffee Ground (SCG) as a Source of Functional Compounds and Growth Substrate for Probiotic Lactic Acid Bacteria","volume":"198","author":"Montemurro","year":"2024","journal-title":"LWT"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/jsfa.12156","article-title":"Development of Solid-State Fermentation Process of Spent Coffee Grounds for the Differentiated Obtaining of Chlorogenic, Quinic, and Caffeic Acids","volume":"103","author":"Altamirano","year":"2023","journal-title":"J. Sci. Food Agric."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Troise, A.D., Salman, M.K., and Vitaglione, P. (2025). Coffee Melanoidins and Gut Health, Royal Society of Chemistry.","DOI":"10.1039\/9781839166853-00133"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Machado, M., Oliveira, M.B.P.P., Ferreira, H., and Alves, R.C. (2025). Prebiotic Potential of Coffee and Coffee By-Products. Coffee in Health and Disease Prevention, Academic Press.","DOI":"10.1016\/B978-0-443-13868-3.00075-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3390\/compounds3010005","article-title":"Polyphenols in Health and Disease: Gut Microbiota, Bioaccessibility, and Bioavailability","volume":"3","author":"Sepodes","year":"2023","journal-title":"Compounds"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rudrapal, M., Rakshit, G., Singh, R.P., Garse, S., Khan, J., Chakraborty, S., Rudrapal, M., Rakshit, G., Singh, R.P., and Garse, S. (2024). Dietary Polyphenols: Review on Chemistry\/Sources, Bioavailability\/Metabolism, Antioxidant Effects, and Their Role in Disease Management. Antioxidants, 13.","DOI":"10.3390\/antiox13040429"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1566524022666211222161637","article-title":"Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation","volume":"23","author":"Sadiq","year":"2023","journal-title":"Curr. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8181","DOI":"10.3390\/ijms12118181","article-title":"Effect of Polyphenols on Oxidative Stress and Mitochondrial Dysfunction in Neuronal Death and Brain Edema in Cerebral Ischemia","volume":"12","author":"Panickar","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1161\/CIRCRESAHA.118.310082","article-title":"Calcium Signaling and Reactive Oxygen Species in Mitochondria","volume":"122","author":"Bertero","year":"2018","journal-title":"Circ. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yilmaz, B.O., Yilmaz, B., and Aydin, Y. (2023). Plant Polyphenols in the Regulation of Ion Channels during Aging and Induced Diseases. Plant Bioactives as Natural Panacea Against Age-Induced Diseases, Elsevier.","DOI":"10.1016\/B978-0-323-90581-7.00021-9"},{"key":"ref_46","unstructured":"Dias, A., and Alexandra, P. (2023). Study of the Mechanisms of Action of Phenolic Compounds on Vascular Smooth Muscle. [Ph.D. Thesis, Charles University]."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Maliougina, M., and El Hiani, Y. (2023). TRPM2: Bridging Calcium and ROS Signaling Pathways\u2014Implications for Human Diseases. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1217828"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e31322","DOI":"10.1002\/jcp.31322","article-title":"TRPM2 Channels Are Essential for Regulation of Cytokine Production in Lung Interstitial Macrophages","volume":"239","author":"Rajan","year":"2024","journal-title":"J. Cell. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Syed Mortadza, S.A., Wang, L., Li, D., and Jiang, L.-H. (2015). TRPM2 Channel-Mediated ROS-Sensitive Ca2+ Signaling Mechanisms in Immune Cells. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00407"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.coi.2020.01.005","article-title":"TRPM2, Linking Oxidative Stress and Ca2+ Permeation to NLRP3 Inflammasome Activation","volume":"62","author":"Wang","year":"2020","journal-title":"Curr. Opin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e70268","DOI":"10.1002\/mco2.70268","article-title":"Oxidative Stress: Signaling Pathways, Biological Functions, and Disease","volume":"6","author":"Liu","year":"2025","journal-title":"MedComm"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Michalak, K.P., and Michalak, A.Z. (2025). Understanding Chronic Inflammation: Couplings between Cytokines, ROS, NO, Cai2+, HIF-1\u03b1, Nrf2 and Autophagy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1558263"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ren, Y., Wang, C., Xu, J., and Wang, S. (2019). Cafestol and Kahweol: A Review on Their Bioactivities and Pharmacological Properties. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174238"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Green, M., Nazemian, V., and Hassan, A. (2025). Peripheral Nerve and Dorsal Root Ganglion (DRG) Pharmacology: Mechanisms, Therapeutic Targets, and Clinical Applications. Mechanisms of Pain, CRC Press.","DOI":"10.1201\/9781003094302-5"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.it.2020.06.012","article-title":"CRAC Channels and Calcium Influx in T Cell-Mediated Immunity","volume":"41","author":"Vaeth","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Rubaiy, H.N. (2023). ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020162"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.1007\/s11064-017-2403-9","article-title":"Differential Molecular Targets for Neuroprotective Effect of Chlorogenic Acid and Its Related Compounds Against Glutamate Induced Excitotoxicity and Oxidative Stress in Rat Cortical Neurons","volume":"42","author":"Rebai","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Piciu, F., Balas, M., Badea, M.A., Cucu, D., Piciu, F., Balas, M., Badea, M.A., and Cucu, D. (2023). TRP Channels in Tumoral Processes Mediated by Oxidative Stress and Inflammation. Antioxidants, 12.","DOI":"10.20944\/preprints202305.1357.v1"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pavl\u00edkov\u00e1, N. (2022). Caffeic Acid and Diseases\u2014Mechanisms of Action. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010588"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Feske, S. (2013). Ca2+ Influx in T Cells: How Many Ca2+ Channels?. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00099"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ferreira, C., Vieira, P., S\u00e1, H., Malva, J., Castelo-Branco, M., Reis, F., and Viana, S. (2024). Polyphenols: Immunonutrients Tipping the Balance of Immunometabolism in Chronic Diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1360065"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Silva-Picazo, K., Allan, E.R.O., Silva-Picazo, K., and Allan, E.R.O. (2025). The Role of TRPV1 in Type 1 Diabetes. Biology, 14.","DOI":"10.3390\/biology14121798"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00281-015-0529-x","article-title":"Potential Therapeutic Value of TRPV1 and TRPA1 in Diabetes Mellitus and Obesity","volume":"38","author":"Derbenev","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Shuba, Y.M. (2021). Beyond Neuronal Heat Sensing: Diversity of TRPV1 Heat-Capsaicin Receptor-Channel Functions. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.612480"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yao, K., Dou, B., Zhang, Y., Chen, Z., Li, Y., Fan, Z., Ma, Y., Du, S., Wang, J., and Xu, Z. (2023). Inflammation\u2014The Role of TRPA1 Channel. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1093925"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cao, D.-S., Zhong, L., Hsieh, T.-H., Abooj, M., Bishnoi, M., Hughes, L., and Premkumar, L.S. (2012). Expression of Transient Receptor Potential Ankyrin 1 (TRPA1) and Its Role in Insulin Release from Rat Pancreatic Beta Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038005"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, M.C., Soczek, S.H.S., Pontes, J.P., Marques, L.A.C., Santos, G.S., Sim\u00e3o, G., Bueno, L.R., Maria-Ferreira, D., Muscar\u00e1, M.N., and Fernandes, E.S. (2022). An Overview of the TRP-Oxidative Stress Axis in Metabolic Syndrome: Insights for Novel Therapeutic Approaches. Cells, 11.","DOI":"10.3390\/cells11081292"},{"key":"ref_68","unstructured":"Caprioli, G., Angeloni, S., Kamgang Nzekoue, A.F., Navarini, L., Sagratini, G., and Vittori, S. (2019). Simultaneous Quantification of 30 Different Bioactive Compounds Including Polyphenols in Spent Coffee Ground and Coffee Silverskin by HPLC-MS\/MS Triple Quadrupole, PRT."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Nilius, B., and Flockerzi, V. (2014). TRP Modulation by Natural Compounds. Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume II, Springer International Publishing.","DOI":"10.1007\/978-3-319-05161-1"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Huang, P., Qu, C., Rao, Z., Wu, D., and Zhao, J. (2024). Bidirectional Regulation Mechanism of TRPM2 Channel: Role in Oxidative Stress, Inflammation and Ischemia-Reperfusion Injury. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1391355"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/mi.2016.60","article-title":"TRPM2 Ion Channels Regulate Macrophage Polarization and Gastric Inflammation During Helicobacter pylori Infection","volume":"10","author":"Beceiro","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chirra, M., Newton, H.S., Gawali, V.S., Wise-Draper, T.M., Chimote, A.A., Conforti, L., Chirra, M., Newton, H.S., Gawali, V.S., and Wise-Draper, T.M. (2022). How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity. Cancers, 14.","DOI":"10.3390\/cancers14153564"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s00232-022-00276-4","article-title":"Functional Potassium Channels in Macrophages","volume":"256","author":"Man","year":"2023","journal-title":"J. Membr. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/ddr.20467","article-title":"The Lymphocyte Potassium Channels Kv1.3 and KCa3.1 as Targets for Immunosuppression","volume":"72","author":"Lam","year":"2011","journal-title":"Drug Dev. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/14728222.2024.2315021","article-title":"Kv1.3 in the Spotlight for Treating Immune Diseases","volume":"28","author":"Capera","year":"2024","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.crohns.2014.04.003","article-title":"Expression of T-Cell KV1.3 Potassium Channel Correlates with pro-Inflammatory Cytokines and Disease Activity in Ulcerative Colitis","volume":"8","author":"Hansen","year":"2014","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Richter-Laskowska, M., Trybek, P., Delfino, D.V., Wawrzkiewicz-Ja\u0142owiecka, A., Richter-Laskowska, M., Trybek, P., Delfino, D.V., and Wawrzkiewicz-Ja\u0142owiecka, A. (2023). Flavonoids as Modulators of Potassium Channels. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021311"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1152\/physiol.00010.2022","article-title":"Kv1.3 K+ Channel Physiology Assessed by Genetic and Pharmacological Modulation","volume":"38","author":"Varanita","year":"2023","journal-title":"Physiology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/14728222.2017.1420170","article-title":"Kv1.3: A Multifunctional Channel with Many Pathological Implications","volume":"22","author":"Estadella","year":"2018","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1517\/14728222.2016.1112792","article-title":"The Voltage-Gated Potassium Channel Kv1.3 Is a Promising Multitherapeutic Target Against Human Pathologies","volume":"20","author":"Capera","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Feske, S., Colucci, F., and Coetzee, W.A. (2024). Do KATP Channels Have a Role in Immunity?. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1484971"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.atherosclerosis.2012.11.016","article-title":"Up-Regulated ATP-Sensitive Potassium Channels Play a Role in Increased Inflammation and Plaque Vulnerability in Macrophages","volume":"226","author":"Ling","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wood dos Santos, T., Cristina Pereira, Q., Teixeira, L., Gambero, A., A. Villena, J., and Lima Ribeiro, M. (2018). Effects of Polyphenols on Thermogenesis and Mitochondrial Biogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092757"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1080\/10408398.2022.2124231","article-title":"Short-Chain Fatty Acid: An Updated Review on Signaling, Metabolism, and Therapeutic Effects","volume":"64","author":"Rekha","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1089\/ars.2017.7404","article-title":"Mitochondria-Centric Review of Polyphenol Bioactivity in Cancer Models","volume":"29","author":"Stevens","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_86","unstructured":"Mart\u00ednez S\u00e1ez, N. (2017). Development of Sustainable Novel Foods Based on Coffee By-Products for Chronic Diseases. [Ph.D. Thesis, Autonomous University of Madrid]."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Kim, H., Kim, S.R., Jung, U.J., Kim, H., Kim, S.R., and Jung, U.J. (2025). Coffee and Its Major Polyphenols in the Prevention and Management of Type 2 Diabetes: A Comprehensive Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125544"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"174553","DOI":"10.1016\/j.ejphar.2021.174553","article-title":"TRPA1: Pharmacology, Natural Activators and Role in Obesity Prevention","volume":"912","author":"Mahajan","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s42003-025-08469-y","article-title":"Reduced Maternal SCFAs in GDM Diminish GPR43 Signaling and Induce Offspring CAKUT","volume":"8","author":"Wang","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ang, Z., and Ding, J.L. (2016). GPR41 and GPR43 in Obesity and Inflammation\u2014Protective or Causative?. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00028"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.2337\/db14-1938","article-title":"GPR43 Potentiates \u03b2-Cell Function in Obesity","volume":"64","author":"McNelis","year":"2015","journal-title":"Diabetes"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.tem.2015.07.009","article-title":"GPR43\u2014A Prototypic Metabolite Sensor Linking Metabolic and Inflammatory Diseases","volume":"26","author":"McKenzie","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pasquini, S., Contri, C., Borea, P.A., Vincenzi, F., Varani, K., Pasquini, S., Contri, C., Borea, P.A., Vincenzi, F., and Varani, K. (2021). Adenosine and Inflammation: Here, There and Everywhere. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147685"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00011-022-01607-w","article-title":"The Role of Adenosine A1 Receptor on Immune Cells","volume":"71","author":"Zhong","year":"2022","journal-title":"Inflamm. Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Marcinek, K., Luzak, B., Rozalski, M., Marcinek, K., Luzak, B., and Rozalski, M. (2024). The Effects of Caffeine on Blood Platelets and the Cardiovascular System through Adenosine Receptors. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202406.1844.v1"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Rembia\u0142kowska, N., Demiy, A., D\u0105browska, A., Mastalerz, J., Szlasa, W., Rembia\u0142kowska, N., Demiy, A., D\u0105browska, A., Mastalerz, J., and Szlasa, W. (2025). Caffeine as a Modulator in Oncology: Mechanisms of Action and Potential for Adjuvant Therapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136252"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ruggiero, M., Calvello, R., Porro, C., Messina, G., Cianciulli, A., Panaro, M.A., Ruggiero, M., Calvello, R., Porro, C., and Messina, G. (2022). Neurodegenerative Diseases: Can Caffeine Be a Powerful Ally to Weaken Neuroinflammation?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112958"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1146\/annurev-immunol-051116-052235","article-title":"Metabolite-Sensing G Protein\u2013Coupled Receptors\u2014Facilitators of Diet-Related Immune Regulation","volume":"35","author":"Tan","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Bevilacqua, E., Cruzat, V., Singh, I., Rose\u2019Meyer, R.B., Panchal, S.K., Brown, L., Bevilacqua, E., Cruzat, V., Singh, I., and Rose\u2019Meyer, R.B. (2023). The Potential of Spent Coffee Grounds in Functional Food Development. Nutrients, 15.","DOI":"10.3390\/nu15040994"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"10164","DOI":"10.1080\/10408398.2023.2221734","article-title":"Mechanisms of Action of Coffee Bioactive Compounds\u2014A Key to Unveil the Coffee Paradox","volume":"64","author":"Machado","year":"2024","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1124\/jpet.122.242570","article-title":"Calcium-Dependent Regulation of G Protein-Coupled Receptor Kinases","volume":"385","author":"Komolov","year":"2023","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Nocella, C., D\u2019Amico, A., Cammisotto, V., Bartimoccia, S., Castellani, V., Loffredo, L., Marini, L., Ferrara, G., Testa, M., and Motta, G. (2023). Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies. Antioxidants, 12.","DOI":"10.3390\/antiox12020429"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Kury\u0142owicz, A., Ko\u017aniewski, K., Kury\u0142owicz, A., and Ko\u017aniewski, K. (2020). Anti-Inflammatory Strategies Targeting Metaflammation in Type 2 Diabetes. Molecules, 25.","DOI":"10.3390\/molecules25092224"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Liu, R., and Nikolajczyk, B.S. (2019). Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01587"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/10408398.2020.1815644","article-title":"Plant Polyphenols Mechanisms of Action on Insulin Resistance and against the Loss of Pancreatic Beta Cells","volume":"62","author":"Papuc","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Wang, Y., Liu, Q., Kang, S.-G., Huang, K., Tong, T., Wang, Y., Liu, Q., Kang, S.-G., Huang, K., and Tong, T. (2021). Dietary Bioactive Ingredients Modulating the CAMP Signaling in Diabetes Treatment. Nutrients, 13.","DOI":"10.3390\/nu13093038"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1111\/bph.15018","article-title":"Mitochondrial Ion Channels in Pancreatic \u03b2-Cells: Novel Pharmacological Targets for the Treatment of Type 2 Diabetes","volume":"178","author":"Wiederkehr","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/nutrit\/nuy014","article-title":"Coffee Consumption and Reduced Risk of Developing Type 2 Diabetes: A Systematic Review with Meta-Analysis","volume":"76","author":"Larsson","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/ajcn\/nqz346","article-title":"Coffee and Type 2 Diabetes: Time to Consider Alternative Mechanisms?","volume":"111","author":"Cornelis","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Batty, M., Bennett, M.R., Yu, E., Batty, M., Bennett, M.R., and Yu, E. (2022). The Role of Oxidative Stress in Atherosclerosis. Cells, 11.","DOI":"10.3390\/cells11233843"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.2174\/1381612823666170329142936","article-title":"The Potential Protective Effects of Phenolic Compounds Against Low-Density Lipoprotein Oxidation","volume":"23","author":"Amarowicz","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8394818","DOI":"10.1155\/2018\/8394818","article-title":"The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases","volume":"2018","author":"Li","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Tauil, R.B., Golono, P.T., de Lima, E.P., de Alvares Goulart, R., Guiguer, E.L., Bechara, M.D., Nicolau, C.C.T., Yanaguizawa Junior, J.L., Fiorini, A.M.R., and M\u00e9ndez-S\u00e1nchez, N. (2024). Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols. Pharmaceuticals, 17.","DOI":"10.3390\/ph17101354"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Bowirrat, A. (2022). Immunosenescence and Aging: Neuroinflammation Is a Prominent Feature of Alzheimer\u2019s Disease and Is a Likely Contributor to Neurodegenerative Disease Pathogenesis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12111817"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Merighi, S., Travagli, A., Nigro, M., Pasquini, S., Cappello, M., Contri, C., Varani, K., Vincenzi, F., Borea, P.A., and Gessi, S. (2023). Caffeine for Prevention of Alzheimer\u2019s Disease: Is the A2A Adenosine Receptor Its Target?. Biomolecules, 13.","DOI":"10.3390\/biom13060967"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Ikram, M., Park, T.J., Ali, T., Kim, M.O., Ikram, M., Park, T.J., Ali, T., and Kim, M.O. (2020). Antioxidant and Neuroprotective Effects of Caffeine against Alzheimer\u2019s and Parkinson\u2019s Disease: Insight into the Role of Nrf-2 and A2AR Signaling. Antioxidants, 9.","DOI":"10.3390\/antiox9090902"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4761081","DOI":"10.1155\/2017\/4761081","article-title":"Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases","volume":"2017","author":"Madeira","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Zhong, H., Xu, J., Yang, M., Hussain, M., Liu, X., Feng, F., Guan, R., Zhong, H., Xu, J., and Yang, M. (2023). Protective Effect of Anthocyanins against Neurodegenerative Diseases through the Microbial-Intestinal-Brain Axis: A Critical Review. Nutrients, 15.","DOI":"10.3390\/nu15030496"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Kim, Y., Cho, A.Y., Kim, H.C., Ryu, D., Jo, S.A., Jung, Y.-S., Kim, Y., Cho, A.Y., Kim, H.C., and Ryu, D. (2022). Effects of Natural Polyphenols on Oxidative Stress-Mediated Blood-Brain Barrier Dysfunction. Antioxidants, 11.","DOI":"10.3390\/antiox11020197"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jclepro.2018.11.230","article-title":"Food Waste Valorization Advocating Circular Bioeconomy\u2014A Critical Review of Potentialities and Perspectives of Spent Coffee Grounds Biorefinery","volume":"211","author":"Zabaniotou","year":"2019","journal-title":"J. Clean. Prod."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"L5","DOI":"10.1186\/2193-1801-4-S1-L5","article-title":"Two Steps Forward, One Step Back: Successes and Failures in Structure-Based Discovery of GPCR Ligands","volume":"4","author":"Carlsson","year":"2015","journal-title":"SpringerPlus"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Cho, Y.Y., Kim, S., Kim, P., Jo, M.J., Park, S.-E., Choi, Y., Jung, S.M., and Kang, H.J. (2025). G-Protein-Coupled Receptor (GPCR) Signaling and Pharmacology in Metabolism: Physiology, Mechanisms, and Therapeutic Potential. Biomolecules, 15.","DOI":"10.3390\/biom15020291"},{"key":"ref_123","unstructured":"Battelli, M. (2024). Plant Secondary Metabolites as A Strategy to Reduce Methane Emissions and Improve Feed Efficiency in Ruminants. [Ph.D. Thesis, Universit\u00e0 Degli Studi di Milano]."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"35776","DOI":"10.1007\/s11356-018-2359-6","article-title":"Converting Environmental Risks to Benefits by Using Spent Coffee Grounds (SCG) as a Valuable Resource","volume":"25","author":"Stylianou","year":"2018","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1080\/15422119.2022.2027444","article-title":"Green Extraction Methods for Isolation of Bioactive Substances from Coffee Seed and Spent","volume":"52","author":"Mediani","year":"2023","journal-title":"Sep. Purif. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:02:53Z","timestamp":1780405373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":125,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114980"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114980","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]}}}