{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T15:28:16Z","timestamp":1776180496857,"version":"3.50.1"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNS2022-135588 MCIN\/AEI\/10.13039\/501100011033","award":["FJC2021-046684-I"],"award-info":[{"award-number":["FJC2021-046684-I"]}]},{"name":"European UnionNextGenerationEU\/PRTR","award":["FJC2021-046684-I"],"award-info":[{"award-number":["FJC2021-046684-I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Lipophenols, combining phenolic and lipid moieties in a single molecule, are valuable candidates for providing enhanced bioactive properties with therapeutic potential, including anti-inflammatory functions associated with immune-mediated diseases such as intestinal bowel disease (IBD). Thus, palmitoyl\u2013epigallocatechin gallate (PEGCG), a lipophilic derivative of epigallocatechin gallate (EGCG), has been highlighted for its enhanced stability in lipid-rich environments and bioavailability due to improved cellular uptake. However, the contribution of lipophilic esterification to PEGCG\u2019s capacity to inhibit inflammation and the development of harmful autoimmune responses remains underexplored. This work uncovered the differential efficiency of EGCG and its palmitoyl derivative in modulating, in vitro, the interleukin profile generated by intestinal epithelium under inflammatory conditions. Therefore, both could attenuate the immune response by lowering macrophage migration and polarisation towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. While the fatty acid moiety gave PEGCG a functional advantage over EGCG in adjusting the interleukin-based response of intestinal epithelium to inflammation\u2014since both of them decreased, to a similar extent, the expression of pro-inflammatory interleukins, namely IL-6, IL-17, IL-18, IL-23, and TNF-\u03b1 (which lowered by 11.2%, on average)\u2014the former was significantly more efficient in cushioning the increase in IL-1\u03b2 and IL-12p70 (by 9.2% and 10.4%, respectively). This immune modulation capacity did not significantly impact the migration and expression of costimulatory molecules featuring M1 (CD86+) or M2 (CD206+) phenotypes by THP-1-derived macrophages, for which both bioactive compounds exhibited equivalent efficiency. Nonetheless, the analysis of the pro- and anti-inflammatory interleukins secreted by differentiated macrophages allowed the identification of an advantage for PEGCG, which decreased the expression of the pro-inflammatory immune mediators IL-1\u03b2 and IL-12p70, IL-23, and TNF-\u03b1 more efficiently. These results suggest that lipophilisation of phenolic compounds presents exciting potential for extending their application as functional molecules by combining the effects of their polar head with their ability to interfere with membranes, conveyed by their lipophilic tail. In addition, the enhanced reactivity would confer a higher capacity to interact with cellular signalling molecules and thus inhibit or attenuate the immune response, which is of special interest for preventing the onset and severity of immune-mediated pathologies such as IBD.<\/jats:p>","DOI":"10.3390\/biom15081208","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T15:19:02Z","timestamp":1755789542000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Palmitic Acid Esterification Boosts Epigallocatechin Gallate\u2019s Immunomodulatory Effects in Intestinal Inflammation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6232-712X","authenticated-orcid":false,"given":"Ra\u00fal","family":"Dom\u00ednguez-Perles","sequence":"first","affiliation":[{"name":"Laboratorio de Fitoqu\u00edmica y Alimentos Saludables (LabFAS), CSIC, CEBAS, Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6358-3694","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Medrano-Padial","sequence":"additional","affiliation":[{"name":"Laboratorio de Fitoqu\u00edmica y Alimentos Saludables (LabFAS), CSIC, CEBAS, Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-3917","authenticated-orcid":false,"given":"Cristina","family":"Garc\u00eda-Viguera","sequence":"additional","affiliation":[{"name":"Laboratorio de Fitoqu\u00edmica y Alimentos Saludables (LabFAS), CSIC, CEBAS, Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7231-6480","authenticated-orcid":false,"given":"Sonia","family":"Medina","sequence":"additional","affiliation":[{"name":"Laboratorio de Fitoqu\u00edmica y Alimentos Saludables (LabFAS), CSIC, CEBAS, Campus Universitario de Espinardo, Edificio 25, 30100 Murcia, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1053\/j.gastro.2016.10.020","article-title":"Understanding and Preventing the Global Increase of Inflammatory Bowel Disease","volume":"152","author":"Kaplan","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41586-025-08940-0","article-title":"Global Evolution of Inflammatory Bowel Disease across Epidemiologic Stages","volume":"642","author":"Hracs","year":"2025","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Holman, J., Hurd, M., Moses, P.L., Mawe, G.M., Zhang, T., Ishaq, S.L., and Li, Y. 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