{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:50:33Z","timestamp":1790844633957,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["5056\/B\/P01\/2011\/40"],"award-info":[{"award-number":["5056\/B\/P01\/2011\/40"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seventh Framework Programme","award":["FP7-REGPOT-2010-1-264103"],"award-info":[{"award-number":["FP7-REGPOT-2010-1-264103"]}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["838991"],"award-info":[{"award-number":["838991"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RyC-2015-18083"],"award-info":[{"award-number":["RyC-2015-18083"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Caffeic acid is one of the most abundant hydroxycinnamic acids in fruits, vegetables, and beverages. This phenolic compound reaches relevant concentrations in the colon (up to 126 \u00b5M) where it could come into contact with the intestinal cells and exert its anti-inflammatory effects. The aim of this investigation was to study the capacity of caffeic acid, at plausible concentrations from an in vivo point of view, to modulate mechanisms related to intestinal inflammation. Consequently, we tested the effects of caffeic acid (50\u201310 \u00b5M) on cyclooxygenase (COX)-2 expression and prostaglandin (PG)E2, cytokines, and chemokines (IL-8, monocyte chemoattractant protein-1 -MCP-1-, and IL-6) biosynthesis in IL-1\u03b2-treated human myofibroblasts of the colon, CCD-18Co. Furthermore, the capacity of caffeic acid to inhibit the angiotensin-converting enzyme (ACE) activity, to hinder advanced glycation end product (AGE) formation, as well as its antioxidant, reducing, and chelating activity were also investigated. Our results showed that (i) caffeic acid targets COX-2 and its product PGE2 as well as the biosynthesis of IL-8 in the IL-1\u03b2-treated cells and (ii) inhibits AGE formation, which could be related to (iii) the high chelating activity exerted. Low anti-ACE, antioxidant, and reducing capacity of caffeic acid was also observed. These effects of caffeic acid expands our knowledge on anti-inflammatory mechanisms against intestinal inflammation.<\/jats:p>","DOI":"10.3390\/nu13020554","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T02:08:12Z","timestamp":1613268492000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Caffeic Acid Modulates Processes Associated with Intestinal Inflammation"],"prefix":"10.3390","volume":"13","author":[{"given":"Danuta","family":"Zieli\u0144ska","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Warmia and Mazury, 10-727 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henryk","family":"Zieli\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-2552","authenticated-orcid":false,"given":"Jos\u00e9 Mois\u00e9s","family":"Laparra-Llopis","sequence":"additional","affiliation":[{"name":"Group of Molecular Immunonutrition in Cancer, Madrid Institute for Advanced Studies in Food (IMDEA-Food), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Szawara-Nowak","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Honke","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-8764","authenticated-orcid":false,"given":"Juan Antonio","family":"Gim\u00e9nez-Bastida","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Science, 10-748 Olsztyn, Poland"},{"name":"Group on Quality, Safety and Bioactivity of Plant Foods, Centro de Edafolog\u00eda y Biolog\u00eda Aplicada del Segura (CSIC), 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","article-title":"The Global, Regional, and National Burden of Inflammatory Bowel Disease in 195 Countries and Territories, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"5","author":"Alatab","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2754","DOI":"10.1038\/s41598-020-59623-x","article-title":"Dietary AGEs Involvement in Colonic Inflammation and Cancer: Insights from an in Vitro Enterocyte Model","volume":"10","author":"Geicu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41590-019-0415-0","article-title":"Targeting Immune Cell Circuits and Trafficking in Inflammatory Bowel Disease","volume":"20","author":"Neurath","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.3748\/wjg.v18.i28.3635","article-title":"Cellular and Molecular Mechanisms of Intestinal Fibrosis","volume":"18","author":"Speca","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1136\/flgastro-2019-101218","article-title":"How to Manage IBD in the \u201cElderly\u201d","volume":"11","author":"Segal","year":"2020","journal-title":"Frontline Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.2174\/0929867324666171009100900","article-title":"Potential of Plant-Sourced Phenols for Inflammatory Bowel Disease","volume":"25","author":"Xiao","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10877","DOI":"10.1021\/jf301807g","article-title":"Biosynthesis, Natural Sources, Dietary Intake, Pharmacokinetic Properties, and Biological Activities of Hydroxycinnamic Acids","volume":"60","author":"Khalifa","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1007\/s10620-017-4620-0","article-title":"Influence of Diet on the Course of Inflammatory Bowel Disease","volume":"62","author":"Tasson","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1136\/gutjnl-2014-307410","article-title":"Environmental Risk Factors in Inflammatory Bowel Disease: A Population-Based Case-Control Study in Asia-Pacific","volume":"64","author":"Ng","year":"2015","journal-title":"Gut"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.freeradbiomed.2004.11.020","article-title":"Human Fecal Water Content of Phenolics: The Extent of Colonic Exposure to Aromatic Compounds","volume":"38","author":"Jenner","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1111\/1541-4337.12518","article-title":"Bioavailability and Metabolism of Chlorogenic Acids (Acyl-Quinic Acids) in Humans","volume":"19","author":"Clifford","year":"2020","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"605","DOI":"10.3181\/0901-RM-1","article-title":"Increased CYP4B1 MRNA Is Associated with the Inhibition of Dextran Sulfate Sodium-Induced Colitis by Caffeic Acid in Mice","volume":"234","author":"Ye","year":"2009","journal-title":"Exp. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31790","DOI":"10.18632\/oncotarget.9306","article-title":"Caffeic Acid Ameliorates Colitis in Association with Increased Akkermansia Population in the Gut Microbiota of Mice","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sadeghi Ekbatan, 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_15","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1080\/01635581.2015.1004736","article-title":"Effects of Caffeic and 5-Caffeoylquinic Acids on Cell Viability and Cellular Uptake in Human Colon Adenocarcinoma Cells","volume":"67","author":"Murad","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1021\/jf073168d","article-title":"5-Caffeoylquinic Acid and Caffeic Acid down-Regulate the Oxidative Stress- and TNF-Alpha-Induced Secretion of Interleukin-8 from Caco-2 Cells","volume":"56","author":"Zhao","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Shin, H.S., Satsu, H., Bae, M.-J., Totsuka, M., and Shimizu, M. (2017). Catechol Groups Enable Reactive Oxygen Species Scavenging-Mediated Suppression of PKD-NFkappaB-IL-8 Signaling Pathway by Chlorogenic and Caffeic Acids in Human Intestinal Cells. Nutrients, 9.","DOI":"10.3390\/nu9020165"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.pharmthera.2006.12.004","article-title":"Role of Intestinal Subepithelial Myofibroblasts in Inflammation and Regenerative Response in the Gut","volume":"114","author":"Andoh","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gim\u00e9nez-Bastida, J.A., Zielinski, H., Piskula, M., Zielinska, D., and Szawara-Nowak, D. (2017). Buckwheat Bioactive Compounds, Their Derived Phenolic Metabolites and Their Health Benefits. Mol. Nutr. Food Res., 61.","DOI":"10.1002\/mnfr.201600475"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zielinska, D., Laparra-Llopis, J.M., Zielinski, H., Szawara-Nowak, D., and Gim\u00e9nez-Bastida, J.A. (2019). Role of Apple Phytochemicals, Phloretin and Phloridzin, in Modulating Processes Related to Intestinal Inflammation. Nutrients, 11.","DOI":"10.3390\/nu11051173"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8866","DOI":"10.1021\/jf300290f","article-title":"Intestinal Ellagitannin Metabolites Ameliorate Cytokine-Induced Inflammation and Associated Molecular Markers in Human Colon Fibroblasts","volume":"60","author":"Larrosa","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2003.08.013","article-title":"Use of Aminoguanidine (Pimagedine) to Prevent the Formation of Advanced Glycation Endproducts","volume":"419","author":"Thornalley","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.foodchem.2005.06.006","article-title":"A Rapid, Simple and Sensitive Fluorescence Method for the Assay of Angiotensin-I Converting Enzyme","volume":"97","author":"Sentandreu","year":"2006","journal-title":"Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0889-1575(03)00066-8","article-title":"Vitamin C and Flavonoid Levels of Fruits and Vegetables Consumed in Hawaii","volume":"17","author":"Franke","year":"2004","journal-title":"J. Food Compos. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a Free Radical Method to Evaluate Antioxidant Activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT Food Sci. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.foodchem.2010.06.051","article-title":"Antioxidant Activity of Flavone C-Glucosides Determined by Updated Analytical Strategies","volume":"124","year":"2011","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0076-6879(99)99005-5","article-title":"[2] Ferric reducing\/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration","volume":"Volume 299","author":"Benzie","year":"1999","journal-title":"Methods in Enzymology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.freeradbiomed.2010.06.010","article-title":"Cardiovascular Effects of Flavonoids Are Not Caused Only by Direct Antioxidant Activity","volume":"49","author":"Mladenka","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ebiom.2018.08.040","article-title":"COX-2-PGE2 Signaling Impairs Intestinal Epithelial Regeneration and Associates with TNF Inhibitor Responsiveness in Ulcerative Colitis","volume":"36","author":"Li","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.bcp.2010.04.033","article-title":"Role of Eicosanoids on Intestinal Epithelial Homeostasis","volume":"80","author":"Ferrer","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nrc.2016.4","article-title":"Aspirin and Colorectal Cancer: The Promise of Precision Chemoprevention","volume":"16","author":"Drew","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1016\/j.bcp.2004.08.002","article-title":"Anti-Inflammatory Effect of Caffeic Acid Methyl Ester and Its Mode of Action through the Inhibition of Prostaglandin E2, Nitric Oxide and Tumor Necrosis Factor-Alpha Production","volume":"68","author":"Shin","year":"2004","journal-title":"Biochem. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"518183","DOI":"10.1155\/2013\/518183","article-title":"IRAK1\/4-Targeted Anti-Inflammatory Action of Caffeic Acid","volume":"2013","author":"Yang","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1017\/S0007114510000826","article-title":"NF-KappaB-Dependent Anti-Inflammatory Activity of Urolithins, Gut Microbiota Ellagic Acid-Derived Metabolites, in Human Colonic Fibroblasts","volume":"104","author":"Larrosa","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/jphp.12364","article-title":"The Modulatory Effects of Caffeic Acid on Human Monocytes and Its Involvement in Propolis Action","volume":"67","author":"Sforcin","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19867","DOI":"10.1038\/s41598-020-76880-y","article-title":"Toll-like Receptor 4 Regulates Intestinal Fibrosis via Cytokine Expression and Epithelial-Mesenchymal Transition","volume":"10","author":"Jun","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","unstructured":"Cotton, J.A., Platnich, J.M., Muruve, D.A., Jijon, H.B., Buret, A.G., and Beck, P.L. (2020, December 08). Interleukin-8 in Gastrointestinal Inflammation and Malignancy: Induction and Clinical Consequences. Available online: https:\/\/www.dovepress.com\/interleukin-8-in-gastrointestinal-inflammation-and-malignancy-inductio-peer-reviewed-article-IJICMR."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.4049\/jimmunol.161.7.3746","article-title":"Prostaglandin E2 Stimulates IL-8 Gene Expression in Human Colonic Epithelial Cells by a Posttranscriptional Mechanism","volume":"161","author":"Yu","year":"1998","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4168\/aair.2014.6.5.449","article-title":"Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors\/Akt\/NF-\u039aB Pathways in Nasal Polyp-Derived Fibroblasts","volume":"6","author":"Cho","year":"2014","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Weber, L., Hammoud Mahdi, D., Jankuhn, S., Lipowicz, B., and Vissiennon, C. (2019). Bioactive Plant Compounds in Coffee Charcoal (Coffeae Carbo) Extract Inhibit Cytokine Release from Activated Human THP-1 Macrophages. Molecules, 24.","DOI":"10.3390\/molecules24234263"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1007\/s10620-013-2825-4","article-title":"Angiotensin Converting Enzyme-Inhibitor Reduces Colitis Severity in an IL-10 Knockout Model","volume":"58","author":"Sueyoshi","year":"2013","journal-title":"Dig. Dis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1007\/s10620-019-5474-4","article-title":"Impact of Angiotensin II Signaling Blockade on Clinical Outcomes in Patients with Inflammatory Bowel Disease","volume":"64","author":"Jacobs","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1021\/jf052263o","article-title":"Inhibition of Angiotensin Converting Enzyme Activity by Flavanol-Rich Foods","volume":"54","author":"Ottaviani","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ejphar.2014.02.038","article-title":"Antihypertensive Effect of Caffeic Acid and Its Analogs through Dual Renin-Angiotensin-Aldosterone System Inhibition","volume":"730","author":"Bhullar","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"van der Lugt, T., Opperhuizen, A., Bast, A., and Vrolijk, M.F. (2020). Dietary Advanced Glycation Endproducts and the Gastrointestinal Tract. Nutrients, 12.","DOI":"10.3390\/nu12092814"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00217-015-2614-8","article-title":"In Vitro Investigation on the Antiglycative and Carbonyl Trapping Activities of Hydroxytyrosol","volume":"242","author":"Navarro","year":"2016","journal-title":"Eur. Food Res. Technol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.foodchem.2014.11.117","article-title":"Mechanism of Reactive Carbonyl Species Trapping by Hydroxytyrosol under Simulated Physiological Conditions","volume":"175","author":"Navarro","year":"2015","journal-title":"Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Genaro-Mattos, T.C., Maur\u00edcio, \u00c2.Q., Rettori, D., Alonso, A., and Hermes-Lima, M. (2015). Antioxidant Activity of Caffeic Acid against Iron-Induced Free Radical Generation\u2014A Chemical Approach. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142402"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1021\/jf9913110","article-title":"Phenolic Acids and Derivatives: Studies on the Relationship among Structure, Radical Scavenging Activity, and Physicochemical Parameters","volume":"48","author":"Silva","year":"2000","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1021\/jf010830b","article-title":"Free Radical Scavenging and Antioxidative Activity of Caffeic Acid Amide and Ester Analogues: Structure-Activity Relationship","volume":"50","author":"Son","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1021\/jf9503265","article-title":"Effect of Metal Cations on the Chemical Oxidation of Olive O-Diphenols in Model Systems","volume":"44","author":"Romero","year":"1996","journal-title":"J. Agric. Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1021\/acs.jafc.8b03377","article-title":"In Vitro Research on Dietary Polyphenols and Health: A Call of Caution and a Guide on How To Proceed","volume":"66","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/0005-2760(84)90287-X","article-title":"Caffeic Acid Is a Selective Inhibitor for Leukotriene Biosynthesis","volume":"792","author":"Koshihara","year":"1984","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1096\/fj.201601136R","article-title":"Roles of 5-Lipoxygenase and Cyclooxygenase-2 in the Biosynthesis of Hemiketals E2 and D2 by Activated Human Leukocytes","volume":"31","author":"Shibata","year":"2017","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1073\/pnas.1019473108","article-title":"Biosynthesis of Hemiketal Eicosanoids by Cross-over of the 5-Lipoxygenase and Cyclooxygenase-2 Pathways","volume":"108","author":"Griesser","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1021\/acs.orglett.8b01578","article-title":"Total Synthesis and Biological Activity of the Arachidonic Acid Metabolite Hemiketal E2","volume":"20","author":"Boer","year":"2018","journal-title":"Org. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.prostaglandins.2016.09.001","article-title":"Biomimetic Synthesis of Hemiketal Eicosanoids for Biological Testing","volume":"132","author":"Suzuki","year":"2017","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Gim\u00e9nez-Bastida, J.A., Gonz\u00e1lez-Sarr\u00edas, A., Esp\u00edn, J.C., and Schneider, C. (2020). Inhibition of 5-Lipoxygenase-Derived Leukotrienes and Hemiketals as a Novel Anti-Inflammatory Mechanism of Urolithins. Mol. Nutr. Food Res., e2000129.","DOI":"10.1002\/mnfr.202000129"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bcp.2017.04.033","article-title":"The Gut Microbiota: A Key Factor in the Therapeutic Effects of (Poly)Phenols","volume":"139","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1900952","DOI":"10.1002\/mnfr.201900952","article-title":"Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes","volume":"64","author":"Selma","year":"2020","journal-title":"Mol. Nutr. Food Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/2\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:21:19Z","timestamp":1760160079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/2\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,8]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["nu13020554"],"URL":"https:\/\/doi.org\/10.3390\/nu13020554","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,8]]}}}