{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:24Z","timestamp":1760146344140,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T00:00:00Z","timestamp":1729382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Associate Laboratory for Green Chemistry\u2014LAQV","doi-asserted-by":"publisher","award":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"],"award-info":[{"award-number":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT\/MCTES","award":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"],"award-info":[{"award-number":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"]}]},{"name":"FCT","award":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"],"award-info":[{"award-number":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"]}]},{"name":"FCT","award":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"],"award-info":[{"award-number":["UIDP\/50006\/2020","UIDB\/50006\/2020","CQ\/UM(UID\/QUI\/00686\/2020","2023.06595.CEECIND","2022.12302.BD","REQUIMTE 2019-34"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The lipophilization of polyphenols (phenolipids) may increase their affinity for membranes, leading to better antioxidant protection. Cholesteryl esters of caffeic, dihydrocaffeic, homoprotocatechuic and protocatechuic acids were synthetized in a one-step procedure with good to excellent yields of ~50\u201395%. After evaluation of their radical scavenging capacity by the DPPH method and establishing the anodic peak potential by cyclic voltammetry, their antioxidant capacity against AAPH-induced oxidative stress in soybean PC liposomes was determined. Their interaction with the liposomal membrane was studied with the aid of three fluorescence probes located at different depths in the membrane. The cholesteryl esters showed a better or similar radical scavenging capacity to that of \u03b1-tocopherol and a lower anodic peak potential than the corresponding parental phenolic acids. Cholesteryl esters were able to protect liposomes to a similar or greater extent than \u03b1-tocopherol. However, despite their antiradical capacity and being able to penetrate and orientate in the membrane in a parallel position to phospholipids, the antioxidant efficiency of cholesteryl esters was deeply dependent on the phenolipid polyphenolic moiety structure. When incorporated during liposome preparation, cholesteryl protocatechuate and caffeate showed more than double the activity of \u03b1-tocopherol. Thus, cholesteryl phenolipids may protect biomembranes against oxidative stress to a greater extent than \u03b1-tocopherol.<\/jats:p>","DOI":"10.3390\/molecules29204959","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T09:58:24Z","timestamp":1729504704000},"page":"4959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cholesteryl Phenolipids as Potential Biomembrane Antioxidants"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-5072","authenticated-orcid":false,"given":"V\u00e2nia","family":"Costa","sequence":"first","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9614-409X","authenticated-orcid":false,"given":"Marlene","family":"Costa","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"given":"Francisca","family":"Arques","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9907-9518","authenticated-orcid":false,"given":"Mariana","family":"Ferreira","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-6853","authenticated-orcid":false,"given":"Paula","family":"Gameiro","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-6056","authenticated-orcid":false,"given":"Dulce","family":"Geraldo","sequence":"additional","affiliation":[{"name":"Chemistry Centre, University of Minho, Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7779-9250","authenticated-orcid":false,"given":"Lu\u00eds S.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Chemistry Centre, University of Minho, Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1149-6876","authenticated-orcid":false,"given":"F\u00e1tima","family":"Paiva-Martins","sequence":"additional","affiliation":[{"name":"REQUIMTE-LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"ref_1","unstructured":"WHO (2017). Clinical Consortium on Healthy Ageing: Topic Focus: Frailty and Intrinsic Capacity: Report of Consortium Meeting, 1\u20132 December 2016 in Geneva, Switzerland, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14911","DOI":"10.1073\/pnas.1915741117","article-title":"Lower socioeconomic status and the acceleration of aging: An outcome-wide analysis","volume":"117","author":"Steptoe","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.12997\/jla.2024.13.1.2","article-title":"Advances in dyslipidaemia treatments: Focusing on ApoC3 and ANGPTL3 inhibitors","volume":"13","author":"Tomlinson","year":"2024","journal-title":"J. Lipid Atheroscler."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101506","DOI":"10.1016\/j.diabet.2023.101506","article-title":"Steatotic liver disease, MASLD and risk of chronic kidney disease","volume":"50","author":"Bilson","year":"2023","journal-title":"Diabetes Metab."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Habibullah, M., Jemmieh, K., Ouda, A., Haider, M.Z., Malki, M.I., and Elzouki, A.-N. (2024). Metabolic-associated fatty liver disease: A selective review of pathogenesis, diagnostic approaches, and therapeutic strategies. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1291501"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, Y., Fleishman, J.S., Li, T., Li, Y., Ren, Z., Chen, J., and Ding, M. (2024). Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1336216"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9132","DOI":"10.3390\/cimb45110573","article-title":"Molecular Aspects of MAFLD\u2014New Insights on Pathogenesis and Treatment","volume":"45","author":"Filipovic","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00392-020-01709-7","article-title":"NAFLD and cardiovascular diseases: A clinical review","volume":"110","author":"Kasper","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jia, G., Bai, H., Mather, B., Hill, M.A., Jia, G., and Sowers, J.R. (2024). Diabetic vasculopathy: Molecular mechanisms and clinical insights. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020804"},{"key":"ref_10","first-page":"e984","article-title":"Obesity and cardiovascular disease: A scientific statement from the American Heart Association","volume":"143","author":"Poirier","year":"2021","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Toma, L., Stancu, C.S., and Sima, A.V. (2020). Endothelial dysfunction in diabetes is aggravated by glycated lipoproteins; novel molecular therapies. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010018"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1382-6689(01)00118-1","article-title":"The toxicity of antioxidants and their metabolites","volume":"11","author":"Bast","year":"2002","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Al-Madhagi, H., and Masoud, A. (Phytother. Res., 2024). Limitations and Challenges of Antioxidant Therapy, Phytother. Res., online ahead of print.","DOI":"10.1002\/ptr.8335"},{"key":"ref_14","first-page":"726","article-title":"Prooxidant activities of antioxidants and their impact on health","volume":"58","author":"Sotler","year":"2019","journal-title":"Acta Clin. Croat."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chedea, V.S., Tomoiag\u01ce, L.L., Macovei, \u015e.O., M\u01cegureanu, D.C., Iliescu, M.L., Bocsan, I.C., Buzoianu, A.D., Vo\u015floban, C.M., and Pop, R.M. (2021). Antioxidant\/pro-oxidant actions of polyphenols from grapevine and wine by-products-base for complementary therapy in ischemic heart diseases. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.750508"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1080\/19440049.2022.2086711","article-title":"Phenolipids as new food additives: From synthesis to cell-based biological activities","volume":"39","author":"Roszek","year":"2022","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.chemphyslip.2017.05.013","article-title":"Toxicity of phenolipids: Protocatechuic acid alkyl esters trigger disruption of mitochondrial membrane potential and caspase activation in macrophages","volume":"206","author":"Pereira","year":"2017","journal-title":"Chem. Phys. Lipids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.bbamem.2018.12.016","article-title":"Rosmarinic acid and its esters inhibit membrane cholesterol domain formation through an antioxidant mechanism based, in nonlinear fashion, on alkyl chain length","volume":"1861","author":"Sherratt","year":"2019","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lopes, R., Costa, M., Ferreira, M., Gameiro, P., and Paiva-Martins, F. (2021). A new family of hydroxytyrosol phenolipids for the antioxidant protection of liposomal systems. Biochim. Biophys. Acta Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2020.183505"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Lopes, R., Costa, M., Ferreira, M., Gameiro, P., Fernandes, S., Catarino, C., Santos-Silva, A., and Paiva-Martins, F. (2021). Caffeic acid phenolipids in the protection of cell membranes from oxidative injuries. Interaction with the membrane phospholipid bilayer. Biochim. Biophys. Acta (BBA)-Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2021.183727"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0753-3322(00)00011-1","article-title":"Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation","volume":"55","author":"Chalas","year":"2001","journal-title":"Biomed. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.nbt.2009.02.004","article-title":"Efficient enzymatic preparation of hydroxycinnamates in ionic liquids enhances their antioxidant effect on lipoproteins oxidative modification","volume":"26","author":"Katsoura","year":"2009","journal-title":"New Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1021\/jf011250h","article-title":"Antioxidant Activity of Dodecyl Gallate","volume":"50","author":"Kubo","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, J., Gu, S.-S., Pang, N., Wang, F.-Q., Pang, F., Cui, H.-S., Wu, X.-Y., and Wu, F.-A. (2014). Alkyl caffeates improve the antioxidant activity, antitumor property and oxidation stability of edible oil. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095909"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1021\/jf010703f","article-title":"Improved method for the synthesis of trans-feruloyl-\u03b2-sitostanol","volume":"49","author":"Condo","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.foodchem.2014.07.119","article-title":"Synthesis of steryl ferulates with various sterol structures and comparison of their antioxidant activity","volume":"169","author":"Hwang","year":"2015","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12375","DOI":"10.1021\/jf2034237","article-title":"Chemoenzymatic synthesis of phytosteryl ferulates and evaluation of their antioxidant activity","volume":"59","author":"Tan","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1600267","DOI":"10.1002\/ejlt.201600267","article-title":"Enzymatic synthesis of steryl hydroxycinnamates and their antioxidant activity","volume":"119","author":"Liphardt","year":"2017","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.ejmech.2010.12.016","article-title":"Synthesis and antioxidant activity of long chain alkyl hydroxycinnamates","volume":"46","author":"Menezes","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.foodchem.2014.10.016","article-title":"A direct correlation between the antioxidant efficiencies of caffeic acid and its alkyl esters and their concentrations in the interfacial region of olive oil emulsions. The pseudophase model interpretation of the \u201ccut-off\u201d effect","volume":"175","author":"Costa","year":"2015","journal-title":"Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9417","DOI":"10.1039\/C6SM01777K","article-title":"Lipid bilayer thickness determines cholesterol\u2019s location in model membranes","volume":"12","author":"Marquardt","year":"2016","journal-title":"Soft Matter"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106336","DOI":"10.1016\/j.foodhyd.2020.106336","article-title":"Soybean protein isolate hydrolysates-liposomes interactions under oxidation: Mechanistic insights into system stability","volume":"112","author":"Chen","year":"2021","journal-title":"Food Hydrocoll."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cejas, J.P., Rosa, A.S., Nazareno, M.A., Disalvo, E.A., and Frias, M.A. (2021). Interaction of chlorogenic acid with model lipid membranes and its influence on antiradical activity. Biochim. Biophys. Acta Biomembr., 1863.","DOI":"10.1016\/j.bbamem.2020.183484"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0005-2736(98)00127-8","article-title":"Determination of the depth of BODIPY probes in model membranes by parallax analysis of fluorescence quenching","volume":"1375","author":"Kaiser","year":"1998","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/abbi.1994.1039","article-title":"Protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation in phospholipid bilayers","volume":"308","author":"Terao","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0304-4165(02)00528-7","article-title":"Interaction of rifampicin and isoniazid with large unilamellar liposomes: Spectroscopic location studies","volume":"1620","author":"Rodrigues","year":"2003","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Lakowicz, J.R. (2006). Fluorescence Anisotropy BT\u2014Principles of Fluorescence Spectroscopy, Springer.","DOI":"10.1007\/978-0-387-46312-4"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/20\/4959\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:16:59Z","timestamp":1760113019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/20\/4959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,20]]},"references-count":37,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["molecules29204959"],"URL":"https:\/\/doi.org\/10.3390\/molecules29204959","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2024,10,20]]}}}