{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T02:28:18Z","timestamp":1776392898885,"version":"3.51.2"},"reference-count":189,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT national funds (FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior)","award":["UIDB\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020"]}]},{"name":"PT national funds (FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior)","award":["UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDP\/50006\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Natural antioxidants from fruits and vegetables, meats, eggs and fish protect cells from the damage caused by free radicals. They are widely used to reduce food loss and waste, minimizing lipid oxidation, as well as for their effects on health through pharmaceutical preparations. In fact, the use of natural antioxidants is among the main efforts made to relieve the pressure on natural resources and to move towards more sustainable food and pharmaceutical systems. Alternative food waste management approaches include the valorization of by-products as a source of phenolic compounds for functional food formulations. In this review, we will deal with the chemistry of antioxidants, including their molecular structures and reaction mechanisms. The biochemical aspects will also be reviewed, including the effects of acidity and temperature on their partitioning in binary and multiphasic systems. The poor bioavailability of antioxidants remains a huge constraint for clinical applications, and we will briefly describe some delivery systems that provide for enhanced pharmacological action of antioxidants via drug targeting and increased bioavailability. The pharmacological activity of antioxidants can be improved by designing nanotechnology-based formulations, and recent nanoformulations include nanoparticles, polymeric micelles, liposomes\/proliposomes, phytosomes and solid lipid nanoparticles, all showing promising outcomes in improving the efficiency and bioavailability of antioxidants. Finally, an overview of the pharmacological effects, therapeutic properties and future choice of antioxidants will be incorporated.<\/jats:p>","DOI":"10.3390\/biomedicines10123051","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:31:16Z","timestamp":1669609876000},"page":"3051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":134,"title":["Biochemistry of Antioxidants: Mechanisms and Pharmaceutical Applications"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-5626","authenticated-orcid":false,"given":"Sonia","family":"Losada-Barreiro","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica-F\u00edsica, Facultade de Qu\u00edmica, Universidade de Vigo, 36200 Vigo, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0386-7887","authenticated-orcid":false,"given":"Zerrin","family":"Sezgin-Bayindir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, 06560 Ankara, Turkey"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9468-0881","authenticated-orcid":false,"given":"Carlos","family":"Bravo-D\u00edaz","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica-F\u00edsica, Facultade de Qu\u00edmica, Universidade de Vigo, 36200 Vigo, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"806470","DOI":"10.3389\/fphar.2022.806470","article-title":"Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action","volume":"13","author":"Rudrapal","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12937-016-0186-5","article-title":"The importance of antioxidants which play the role in cellular response against oxidative\/nitrosative stress: Current state","volume":"15","author":"Kurutas","year":"2016","journal-title":"Nutr. J."},{"key":"ref_5","first-page":"43","article-title":"Oxidative stress and antioxidant mechanisms in human body","volume":"6","author":"Adwas","year":"2019","journal-title":"J. Appl. Biotechnol. Bioeng."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Costa, M., Losada-Barreiro, S., Paiva-Martins, F., and Bravo-D\u00edaz, C. (2021). Polyphenolic Antioxidants in Lipid Emulsions: Partitioning Effects and Interfacial Phenomena. Foods, 10.","DOI":"10.3390\/foods10030539"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Stromsnes, K., Lagzdina, R., Olaso-Gonzalez, G., Gimeno-Mallench, L., and Gambini, J. (2021). Pharmacological Properties of Polyphenols: Bioavailability, Mechanisms of Action, and Biological Effects in In Vitro Studies, Animal Models, and Humans. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081074"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2174\/1389450115666141024113925","article-title":"Pharmacological applications of antioxidants: Lights and shadows","volume":"15","author":"Saso","year":"2014","journal-title":"Curr. Drug Targets"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Logan, A., Nienaber, U., and Pan, X. (2013). CHAPTER 1\u2014Challenges in Elucidating Lipid Oxidation Mechanisms: When, Where, and How Do Products Arise?. Lipid Oxidation, AOCS Press.","DOI":"10.1016\/B978-0-9830791-6-3.50004-7"},{"key":"ref_10","first-page":"1","article-title":"Advances in the control of lipid peroxidation in oil-in-water emulsions: Kinetic approaches","volume":"1","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shahidi, F. (2005). Lipid Oxidation: Theoretical Aspects. Bailey\u2019s Industrial Oil and Fat Products, John Wiley & Sons.","DOI":"10.1002\/047167849X"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111621","DOI":"10.1016\/j.foodres.2022.111621","article-title":"A unifying approach to lipid oxidation in emulsions: Modelling and experimental validation","volume":"160","year":"2022","journal-title":"Food Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1002\/med.21592","article-title":"The mechanism(s) of action of antioxidants: From scavenging reactive oxygen\/nitrogen species to redox signaling and the generation of bioactive secondary metabolites","volume":"39","author":"Hunyadi","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1515\/bmc-2019-0019","article-title":"Role of Nanomedicine in Redox Mediated Healing at Molecular Level","volume":"10","author":"Adhikari","year":"2019","journal-title":"Biomol. Concepts"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bertelli, A., Biagi, M., Corsini, M., Baini, G., Cappellucci, G., and Miraldi, E. (2021). Polyphenols: From Theory to Practice. Foods, 10.","DOI":"10.3390\/foods10112595"},{"key":"ref_16","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3389\/fphys.2020.00694","article-title":"Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases","volume":"11","author":"Zucca","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s12937-022-00816-7","article-title":"Effects of curcumin and\/or coenzyme Q10 supplementation on metabolic control in subjects with metabolic syndrome: A randomized clinical trial","volume":"21","author":"Sangouni","year":"2022","journal-title":"Nutr. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Iacobini, C., Vitale, M., Haxhi, J., Pesce, C., Pugliese, G., and Menini, S. (2022). Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet. Nutrients, 14.","DOI":"10.3390\/nu14051061"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114510003909","article-title":"Postprandial metabolic events and fruit-derived phenolics: A review of the science","volume":"104","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1080\/10408398.2020.1835819","article-title":"Targets and mechanisms of dietary anthocyanins to combat hyperglycemia and hyperuricemia: A comprehensive review","volume":"62","author":"Yang","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1007\/s00125-003-1225-2","article-title":"Effect of glycated LDL on microvascular tone in mice: A comparative study with LDL modified in vitro or isolated from diabetic patients","volume":"46","author":"Nivoit","year":"2003","journal-title":"Diabetologia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1046\/j.1525-1373.1999.d01-129.x","article-title":"Postprandial Low-Density Lipoproteins in Type 2 Diabetes are Oxidized More Extensively Than Fasting Diabetes and Control Samples","volume":"222","author":"Diwadkar","year":"1999","journal-title":"Proc. Soc. Exp. Boil. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6501046","DOI":"10.1155\/2017\/6501046","article-title":"Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans","volume":"2017","author":"Marrocco","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1096\/fj.201700170R","article-title":"Physiological role of reactive oxygen species as promoters of natural defenses","volume":"31","author":"Roy","year":"2017","journal-title":"FASEB J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.freeradbiomed.2011.05.010","article-title":"Extending life span by increasing oxidative stress","volume":"51","author":"Ristow","year":"2011","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s11101-007-9070-4","article-title":"Flavanols: Digestion, absorption and bioactivity","volume":"7","author":"Hackman","year":"2008","journal-title":"Phytochem. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.jff.2015.06.018","article-title":"Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects\u2014A review","volume":"18","author":"Shahidi","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104392","DOI":"10.1016\/j.jff.2021.104392","article-title":"Health benefits, extraction and development of functional foods with curcuminoids","volume":"79","author":"Munekata","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_30","first-page":"1","article-title":"A biochemical perspective on the fate of virgin olive oil phenolic compounds in vivo","volume":"12","author":"Costa","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1211\/jpp.59.12.0010","article-title":"Antioxidant properties of phenols","volume":"59","author":"Foti","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s00204-011-0774-2","article-title":"Antioxidant activity of food constituents: An overview","volume":"86","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rappoport, Z. (2003). Phenols as antioxidants, in The Chemistry of Phenols, John Wiley & Sons Ltd.","DOI":"10.1002\/0470857277"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11664","DOI":"10.1021\/acs.jpcb.5b05419","article-title":"New Insights on the Biophysical Interaction of Resveratrol with Biomembrane Models: Relevance for Its Biological Effects","volume":"119","author":"Neves","year":"2015","journal-title":"J. Phys. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Meleleo, D. (2021). Study of Resveratrol\u2019s Interaction with Planar Lipid Models: Insights into Its Location in Lipid Bilayers. Membranes, 11.","DOI":"10.3390\/membranes11020132"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1021\/jp208731g","article-title":"Positioning of Antioxidant Quercetin and Its Metabolites in Lipid Bilayer Membranes: Implication for Their Lipid-Peroxidation Inhibition","volume":"116","author":"Berka","year":"2012","journal-title":"J. Phys. Chem. B"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Karonen, M. (2022). Insights into Polyphenol\u2013Lipid Interactions: Chemical Methods, Molecular Aspects and Their Effects on Membrane Structures. Plants, 11.","DOI":"10.3390\/plants11141809"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1016\/j.bbamem.2014.07.001","article-title":"Structure-dependent interactions of polyphenols with a biomimetic membrane system","volume":"1838","author":"Phan","year":"2014","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"183727","DOI":"10.1016\/j.bbamem.2021.183727","article-title":"Caffeic acid phenolipids in the protection of cell membranes from oxidative injuries. Interaction with the membrane phospholipid bilayer","volume":"1863","author":"Lopes","year":"2021","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1002\/ejlt.201400507","article-title":"Distributions of phenolic acid antioxidants between the interfacial and aqueous regions of corn oil emulsions: Effects of pH and emulsifier concentration","volume":"117","author":"Romsted","year":"2015","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/cphc.201500882","article-title":"A Physicochemical Study of the Effects of Acidity on the Distribution and Antioxidant Efficiency of Trolox in Olive Oil-in-Water Emulsions","volume":"17","author":"Galan","year":"2016","journal-title":"ChemPhysChem"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jcis.2012.07.036","article-title":"Effects of emulsifier hydrophile-lipophile balance and emulsifier concentration on the distributions of gallic acid, propyl gallate, and \u03b1-tocopherol in corn oil emulsions","volume":"389","year":"2013","journal-title":"J. Colloid. Int. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1021\/acs.jced.8b00258","article-title":"Differential Partitioning of Bioantioxidants in Edible Oil\u2013Water and Octanol\u2013Water Systems: Linear Free Energy Relationships","volume":"63","year":"2018","journal-title":"J. Chem. Eng. Data"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jodko-Pi\u00f3recka, K., Cedrowski, J., and Litwinienko, G. (2018). Physico-chemical principles of antioxidant action, including solvent and matrix dependence and interfacial phenomena. Measurement of Antioxidant Activity & Capacity, John Wiley & Sons, Inc.","DOI":"10.1002\/9781119135388.ch12"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1021\/ar0682029","article-title":"Solvent Effects on the Rates and Mechanisms of Reaction of Phenols with Free Radicals","volume":"40","author":"Litwinienko","year":"2007","journal-title":"Acc. Chem. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"\u0160egatin, N., \u017dontar, T.P., and Ulrih, N.P. (2020). Dielectric Properties and Dipole Moment of Edible Oils Subjected to \u2018Frying\u2019 Thermal Treatment. Foods, 9.","DOI":"10.3390\/foods9070900"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12346","DOI":"10.1021\/la2025846","article-title":"Are Hydrotropes Distinct from Surfactants?","volume":"27","author":"Eastoe","year":"2011","journal-title":"Langmuir"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s12668-022-00941-x","article-title":"A Comprehensive Review on Novel Liposomal Methodologies, Commercial Formulations, Clinical Trials and Patents","volume":"12","author":"Andra","year":"2022","journal-title":"BioNanoScience"},{"key":"ref_49","unstructured":"Jafar, M.M. (2018). Plant Antioxidants in Food Emulsions. Some New Aspects of Colloidal Systems in Foods, IntechOpen. p. Ch. 2."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cis.2017.12.001","article-title":"Improving emulsion formation, stability and performance using mixed emulsifiers: A review","volume":"251","author":"McClements","year":"2018","journal-title":"Adv. Colloid Interface Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sezgin-Bayindir, Z., Losada-Barreiro, S., Bravo-D\u00edaz, C., Sova, M., Kristl, J., and Saso, L. (2021). Nanotechnology-Based Drug Delivery to Improve the Therapeutic Benefits of NRF2 Modulators in Cancer Therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10050685"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.molliq.2014.12.016","article-title":"Encapsulation and solubilization of the antioxidants gallic acid and ethyl, propyl and butyl gallate with \u03b2-cyclodextrin","volume":"210","year":"2015","journal-title":"J. Mol. Liq."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1021\/cr9700181","article-title":"Structures of the Common Cyclodextrins and Their Larger Analogues Beyond the Doughnut","volume":"98","author":"Saenger","year":"1998","journal-title":"Chem. Rev."},{"key":"ref_54","unstructured":"Szejtli, J., and Osa, T. (1996). Measurement of Cyclodextrin Complex Stability Constants, in Comprehensive Supramolecular Chemistry, Elsevier Sci. Ltd."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1021\/cr960371r","article-title":"The Stability of Cyclodextrin Complexes in Solution","volume":"97","author":"Connors","year":"1997","journal-title":"Chem. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1002\/(SICI)1521-3765(19990702)5:7<2048::AID-CHEM2048>3.0.CO;2-U","article-title":"Dynamic Aspects of Cyclodextrin Host-Guest inclusion as studied nu an EPR Spin-Probe Technique","volume":"5","author":"Lucarini","year":"1999","journal-title":"Chem. Eur. J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-P\u00e9rez, P., Losada-Barreiro, S., Gallego, P.P., and Bravo-D\u00edaz, C. (2019). Cyclodextrin-Elicited Bryophyllum Suspension Cultured Cells: Enhancement of the Production of Bioactive Compounds. Int. J. Mol. Sci., 20.","DOI":"10.20944\/preprints201910.0097.v1"},{"key":"ref_58","first-page":"260","article-title":"Effects of pH and surfactant concentration on the local concentrations of antioxidants in binary oil-water mixtures and in oil-in water emulsions","volume":"50","year":"2018","journal-title":"Bulg. Chem. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Trostchansky, A., and Rubbo, H. (2019). Diffusion and Transport of Reactive Species Across Cell Membranes. Bioactive Lipids in Health and Disease, Springer International Publishing.","DOI":"10.1007\/978-3-030-11488-6"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Stillwell, W. (2016). Membrane Transport. An Introduction to Biological Membranes, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-444-63772-7.00019-1"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-030-11488-6_1","article-title":"Diffusion and Transport of Reactive Species Across Cell Membranes","volume":"1127","author":"Cuevasanta","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Stillwell, W. (2013). Chapter 9\u2014Basic Membrane Properties of the Fluid Mosaic Model. An Introduction to Biological Membranes, Elsevier.","DOI":"10.1016\/B978-0-444-52153-8.00009-X"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3233\/BPL-200099","article-title":"Low Molecular Weight (poly)Phenol Metabolites Across the Blood-Brain Barrier: The Underexplored Journey","volume":"6","author":"Carecho","year":"2020","journal-title":"Brain Plast."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1085\/jgp.100.1.69","article-title":"Is the mammalian cell plasma membrane a barrier to oxygen transport?","volume":"100","author":"Subczynski","year":"1992","journal-title":"J. Gen. Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1006\/abbi.1996.0162","article-title":"Nitric Oxide Diffusion in Membranes Determined by Fluorescence Quenching","volume":"328","author":"Denicola","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.abb.2011.06.003","article-title":"Nitrogen dioxide solubility and permeation in lipid membranes","volume":"512","author":"Signorelli","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.bbagen.2004.04.011","article-title":"A metabolic model describing the H2O2 elimination by mammalian cells including H2O2 permeation through cytoplasmic and peroxisomal membranes: Comparison with experimental data","volume":"1673","author":"Makino","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0005-2736(84)90409-7","article-title":"Permeability of bilayer lipid membranes for superoxide (O2\u2212) radicals","volume":"778","author":"Ivanov","year":"1984","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_69","unstructured":"Van Der Walle, C. (2011). Chapter 8\u2014Nanoparticle Mediated Oral Delivery of Peptides and Proteins: Challenges and Perspectives. Peptide and Protein Delivery, Academic Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s43556-022-00090-3","article-title":"Vesicle trafficking and vesicle fusion: Mechanisms, biological functions, and their implications for potential disease therapy","volume":"3","author":"Cui","year":"2022","journal-title":"Mol. Biomed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/BF00263682","article-title":"Interactions between biliary lipid micelles and intestinal brush border membranes investigated by 1H and 31P nuclear magnetic resonance","volume":"15","author":"Tellier","year":"1987","journal-title":"Eur. Biophys. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1021\/acschemneuro.5b00051","article-title":"Fate of microbial metabolites of dietary polyphenols in rats: Is the brain their target destination?","volume":"6","author":"Gasperotti","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1039\/C7BM00133A","article-title":"Mustard-inspired delivery shuttle for enhanced blood\u2013brain barrier penetration and effective drug delivery in glioma therapy","volume":"5","author":"Wang","year":"2017","journal-title":"Biomater. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3945\/an.114.005231","article-title":"Whole Food versus Supplement: Comparing the Clinical Evidence of Tomato Intake and Lycopene Supplementation on Cardiovascular Risk Factors","volume":"5","author":"Sesso","year":"2014","journal-title":"Adv. Nutr. Int. Rev. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1038\/sj.ejcn.1601822","article-title":"General aspects on the assessment of functional foods in the European Union","volume":"57","author":"Palou","year":"2003","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Rahman, M.M., and Rahaman, M.S. (2021). Role of Phenolic Compounds in Human Disease: Current Knowledge and Future Prospects. Molecules, 27.","DOI":"10.3390\/molecules27010233"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.abb.2010.04.005","article-title":"Antioxidant actions of flavonoids: Thermodynamic and kinetic analysis","volume":"501","author":"Galleano","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.abb.2004.06.008","article-title":"Experimental evidence that flavonoid metal complexes may act as mimics of superoxide dismutase","volume":"428","author":"Kostyuk","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0891-5849(90)90045-K","article-title":"Flavonoids as superoxide scavengers and antioxidants","volume":"9","author":"Yuting","year":"1990","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1021\/np970237h","article-title":"Structure\u2212Activity Relationship and Classification of Flavonoids as Inhibitors of Xanthine Oxidase and Superoxide Scavengers","volume":"61","author":"Cos","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109877","DOI":"10.1016\/j.dyepig.2021.109877","article-title":"Multiple free radical scavenging reactions of flavonoids","volume":"198","author":"Zheng","year":"2022","journal-title":"Dye. Pigment."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"127915","DOI":"10.1016\/j.foodchem.2020.127915","article-title":"Analysis of the interaction between cyanidin-3-O-glucoside and casein hydrolysates and its effect on the antioxidant ability of the complexes","volume":"340","author":"Yin","year":"2020","journal-title":"Food Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0076-6879(90)86128-I","article-title":"Flavonoids as antioxidants: Determination of radical-scavenging efficiencies","volume":"186","author":"Bors","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1002\/ptr.7002","article-title":"Natural products: The role and mechanism in low-density lipoprotein oxidation and atherosclerosis","volume":"35","author":"Zhang","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8670","DOI":"10.1039\/D0FO01690J","article-title":"Protective effect of olive oil polyphenol phase II sulfate conjugates on erythrocyte oxidative-induced hemolysis","volume":"11","author":"Fernandes","year":"2020","journal-title":"Food Funct."},{"key":"ref_86","first-page":"207","article-title":"Bioavailability of phenolic compounds from olive oil and oxidative\/antioxidant status at postprandial state in healthy humans","volume":"30","author":"Weinbrenner","year":"2004","journal-title":"Drugs Under Exp. Clin. Res."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Yerena, A., Vallverd\u00fa-Queralt, A., Lamuela-Ravent\u00f3s, R., and Escribano-Ferrer, E. (2021). LC-ESI-LTQ-Orbitrap-MS for Profiling the Distribution of Oleacein and Its Metabolites in Rat Tissues. Antioxidants, 10.","DOI":"10.3390\/antiox10071083"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/mnfr.200800276","article-title":"Effects of olive oil polyphenols on erythrocyte oxidative damage","volume":"53","author":"Fernandes","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6636","DOI":"10.1021\/jf4016202","article-title":"Protective Activity of Hydroxytyrosol Metabolites on Erythrocyte Oxidative-Induced Hemolysis","volume":"61","author":"Silva","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.freeradbiomed.2004.04.019","article-title":"The increase in human plasma antioxidant capacity after apple consumption is due to the metabolic effect of fructose on urate, not apple-derived antioxidant flavonoids","volume":"37","author":"Lotito","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1749-6632.2002.tb02917.x","article-title":"Wine Polyphenols and Optimal Nutrition","volume":"957","author":"Ursini","year":"2002","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"101649","DOI":"10.1016\/j.arr.2022.101649","article-title":"Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans\u2014Evidence from untargeted mRNA and miRNA studies","volume":"79","author":"Ruskovska","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.foodres.2014.05.009","article-title":"Metabolite profiling of olive oil and thyme phenols after a sustained intake of two phenol-enriched olive oils by humans: Identification of compliance markers","volume":"65","author":"Romero","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.3945\/ajcn.113.076133","article-title":"The food metabolome: A window over dietary exposure","volume":"99","author":"Scalbert","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev-food-030216-025636","article-title":"Anthocyanins and Flavanones Are More Bioavailable than Previously Perceived: A Review of Recent Evidence","volume":"8","author":"Kay","year":"2017","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1093\/jn\/130.11.2765","article-title":"Intestinal Transport of Quercetin Glycosides in Rats Involves Both Deglycosylation and Interaction with the Hexose Transport Pathway","volume":"130","author":"Gee","year":"2000","journal-title":"J. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1017\/S000711451000526X","article-title":"Absorption and metabolism of olive oil secoiridoids in the small intestine","volume":"105","author":"Pinto","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Serreli, G., and Deiana, M. (2018). Biological Relevance of Extra Virgin Olive Oil Polyphenols Metabolites. Antioxidants, 7.","DOI":"10.3390\/antiox7120170"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1124\/dmd.106.014241","article-title":"Interaction of Positional Isomers of Quercetin Glucuronides with the Transporter ABCC2 (cMOAT, MRP2)","volume":"35","author":"Williamson","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/1541-4337.12351","article-title":"The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective","volume":"17","author":"Williamson","year":"2018","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"205ra133","DOI":"10.1126\/scitranslmed.3005870","article-title":"Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence","volume":"5","author":"Patel","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.mam.2018.01.001","article-title":"Flavonoids and the gastrointestinal tract: Local and systemic effects","volume":"61","author":"Oteiza","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5724","DOI":"10.1021\/acs.jafc.6b02088","article-title":"Identification of Plasma and Urinary Metabolites and Catabolites Derived from Orange Juice (Poly)phenols: Analysis by High-Performance Liquid Chromatography\u2013High-Resolution Mass Spectrometry","volume":"64","author":"Ludwig","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Giuliani, C., Marzorati, M., Daghio, M., Franzetti, A., Innocenti, M., Van de Wiele, T., and Mulinacci, N. (2019). Effects of Olive and Pomegranate By-Products on Human Microbiota: A Study Using the SHIME\u00ae In Vitro Simulator. Molecules, 24.","DOI":"10.3390\/molecules24203791"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s11095-013-1222-1","article-title":"Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches","volume":"31","author":"Kim","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jconrel.2020.12.034","article-title":"Nanomedicines accessible in the market for clinical interventions","volume":"330","author":"Gadekar","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jconrel.2020.07.007","article-title":"Delivering the power of nanomedicine to patients today","volume":"326","author":"Germain","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jconrel.2006.04.015","article-title":"Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective","volume":"113","author":"Ratnam","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12951-018-0392-8","article-title":"Nano based drug delivery systems: Recent developments and future prospects","volume":"16","author":"Patra","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.jconrel.2014.04.048","article-title":"Controlled release for local delivery of drugs: Barriers and models","volume":"190","author":"Weiser","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Devarajan, P.V., and Jain, S. (2015). Targeted Drug Delivery Systems: Strategies and Challenges. Targeted Drug Delivery: Concepts and Design, Springer International Publishing.","DOI":"10.1007\/978-3-319-11355-5"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.2174\/092986712800784702","article-title":"Drug-Loaded Nanocarriers: Passive Targeting and Crossing of Biological Barriers","volume":"19","author":"Rabanel","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jconrel.2021.01.017","article-title":"Development of nanoparticle-delivery systems for antiviral agents: A review","volume":"331","author":"Delshadi","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_114","unstructured":"Anand, K. (2021). Chapter 13\u2014Advanced drug delivery applications of self-assembled nanostructures and polymeric nanoparticles. Handbook on Nanobiomaterials for Therapeutics and Diagnostic Applications, Elsevier."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.tips.2009.08.004","article-title":"Liposomes and nanoparticles: Nanosized vehicles for drug delivery in cancer","volume":"30","author":"Malam","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"587997","DOI":"10.3389\/fmolb.2020.587997","article-title":"Solid Lipid Nanoparticles for Drug Delivery: Pharmacological and Biopharmaceutical Aspects","volume":"7","author":"Montoto","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"344","DOI":"10.2174\/1389201016666150206101443","article-title":"Provesicles as novel drug delivery systems","volume":"16","author":"Bayindir","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ejpb.2006.06.003","article-title":"Preparation and characterization of polymeric micelles for solubilization of poorly soluble anticancer drugs","volume":"64","author":"Sezgin","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6983","DOI":"10.2147\/IJN.S318416","article-title":"Phytosomes as Innovative Delivery Systems for Phytochemicals: A Comprehensive Review of Literature","volume":"16","author":"Barani","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jconrel.2010.08.027","article-title":"To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery","volume":"148","author":"Danhier","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2174\/156720112800389089","article-title":"Active targeting strategies for anticancer drug nanocarriers","volume":"9","author":"Basile","year":"2012","journal-title":"Curr. Drug Deliv."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3","DOI":"10.7150\/thno.3463","article-title":"Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy","volume":"2","author":"Yu","year":"2012","journal-title":"Theranostics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/jphp.13098","article-title":"An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites","volume":"71","author":"Attia","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.addr.2020.09.009","article-title":"Polymeric micelles for the delivery of poorly soluble drugs: From nanoformulation to clinical approval","volume":"156","author":"Hwang","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"113868","DOI":"10.1016\/j.addr.2021.113868","article-title":"Phytonanomaterials as therapeutic agents and drug delivery carriers","volume":"176","author":"Xie","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_126","first-page":"57","article-title":"Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery","volume":"16","author":"Zhang","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"119273","DOI":"10.1016\/j.carbpol.2022.119273","article-title":"N-trimethyl chitosan coated targeting nanoparticles improve the oral bioavailability and antioxidant activity of vitexin","volume":"286","author":"Li","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"111016","DOI":"10.1016\/j.msec.2020.111016","article-title":"Resveratrol-loaded folate targeted lipoprotein-mimetic nanoparticles with improved cytotoxicity, antioxidant activity and pharmacokinetic profile","volume":"114","author":"Poonia","year":"2020","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"106297","DOI":"10.1016\/j.ejps.2022.106297","article-title":"Surface modified genistein phytosome for breast cancer treatment: In-vitro appraisal, pharmacokinetics, and in-vivo antitumor efficacy","volume":"179","author":"Komeil","year":"2022","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"111723","DOI":"10.1016\/j.colsurfb.2021.111723","article-title":"PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells","volume":"203","author":"Tian","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"127609","DOI":"10.1016\/j.colsurfa.2021.127609","article-title":"Folic acid decorated pH sensitive polydopamine coated honeycomb structured nickel oxide nanoparticles for targeted delivery of quercetin to triple negative breast cancer cells","volume":"630","author":"Binu","year":"2021","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jconrel.2019.04.018","article-title":"Anti-atherogenic effects of CD36-targeted epigallocatechin gallate-loaded nanoparticles","volume":"303","author":"Zhang","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijpharm.2017.05.058","article-title":"Argpyrimidine-tagged rutin-encapsulated biocompatible (ethylene glycol dimers) nanoparticles: Application for targeted drug delivery in experimental diabetes (Part 2)","volume":"528","author":"Bhattacherjee","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2011.08.032","article-title":"Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications","volume":"420","author":"Kawabata","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.drudis.2014.03.001","article-title":"Ligand-mediated active targeting for enhanced oral absorption","volume":"19","author":"Zhang","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2012.08.042","article-title":"Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs","volume":"453","author":"Lu","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_137","first-page":"G711","article-title":"Electrical charge on protein regulates its absorption from the rat small intestine","volume":"282","author":"Nishikawa","year":"2002","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1080\/10717544.2018.1501119","article-title":"The challenges of oral drug delivery via nanocarriers","volume":"25","author":"Reinholz","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jconrel.2022.05.048","article-title":"Trends in advanced oral drug delivery system for curcumin: A systematic review","volume":"348","author":"Dilokthornsakul","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.ijpharm.2019.05.034","article-title":"Improved oral bioavailability of the anticancer drug catechin using chitosomes: Design, in-vitro appraisal and in-vivo studies","volume":"565","author":"Ezzat","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"110628","DOI":"10.1016\/j.colsurfb.2019.110628","article-title":"Improved cardioprotective effects of hesperidin solid lipid nanoparticles prepared by supercritical antisolvent technology","volume":"187","author":"Saad","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"120036","DOI":"10.1016\/j.ijpharm.2020.120036","article-title":"Enhancement of oral bioavailability and hypoglycemic activity of liquiritin-loaded precursor liposome","volume":"592","author":"Wang","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"121525","DOI":"10.1016\/j.ijpharm.2022.121525","article-title":"Berberine-loaded liposomes for oral delivery: Preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model","volume":"616","author":"Duong","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"102808","DOI":"10.1016\/j.jddst.2021.102808","article-title":"TPGS conjugated pro-liposomal nano-drug delivery system potentiate the antioxidant and hepatoprotective activity of Myricetin","volume":"66","author":"Thant","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"110714","DOI":"10.1016\/j.biopha.2020.110714","article-title":"Pleotropic Effects of Polyphenols in Cardiovascular System","volume":"130","author":"Behl","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"9086947","DOI":"10.1155\/2018\/9086947","article-title":"Hydroxytyrosol Ameliorates Endothelial Function under Inflammatory Conditions by Preventing Mitochondrial Dysfunction","volume":"2018","author":"Calabriso","year":"2018","journal-title":"Oxidat. Med. Cell. Longev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s11684-018-0655-7","article-title":"Resveratrol reduces intracellular reactive oxygen species levels by inducing autophagy through the AMPK-mTOR pathway","volume":"12","author":"Song","year":"2018","journal-title":"Front. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.thromres.2020.07.024","article-title":"The antithrombotic effect of caffeic acid is associated with a cAMP-dependent pathway and clot retraction in human platelets","volume":"195","author":"Nam","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e13602","DOI":"10.1111\/apha.13602","article-title":"EGCG inhibits pressure overload-induced cardiac hypertrophy via the PSMB5\/Nmnat2\/SIRT6-dependent signalling pathways","volume":"231","author":"Cai","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2273000","DOI":"10.1155\/2022\/2273000","article-title":"Protective Effect of Kaempferol and Its Nanoparticles on 5-Fluorouracil-Induced Cardiotoxicity in Rats","volume":"2022","author":"Safarpour","year":"2022","journal-title":"BioMed. Res. Int."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1292\/jvms.20-0245","article-title":"Effects of protocatechuic acid on ameliorating lipid profiles and cardio-protection against coronary artery disease in high fat and fructose diet fed in rats","volume":"82","author":"Li","year":"2020","journal-title":"J. Vet. Med. Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"15607","DOI":"10.1038\/s41598-017-15925-1","article-title":"Gallic Acid Reduces Blood Pressure and Attenuates Oxidative Stress and Cardiac Hypertrophy in Spontaneously Hypertensive Rats","volume":"7","author":"Jin","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.metabol.2012.06.003","article-title":"Ellagic acid inhibits cardiac arrhythmias, hypertrophy and hyperlipidaemia during myocardial infarction in rats","volume":"62","author":"Kannan","year":"2013","journal-title":"Metabolism"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1080\/13880209.2021.2017469","article-title":"Delphinidin-3-O-glucoside, an active compound of Hibiscus sabdariffa calyces, inhibits oxidative stress and inflammation in rabbits with atherosclerosis","volume":"60","author":"Sun","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Quir\u00f3s-Fern\u00e1ndez, R., L\u00f3pez-Plaza, B., Bermejo, L.M., Palma-Milla, S., and G\u00f3mez-Candela, C. (2019). Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial. Nutrients, 11.","DOI":"10.3390\/nu11030640"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1007\/s00394-022-02823-0","article-title":"The intake of flavonoids, stilbenes, and tyrosols, mainly consumed through red wine and virgin olive oil, is associated with lower carotid and femoral subclinical atherosclerosis and coronary calcium","volume":"61","author":"Salazar","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.ejmech.2018.12.016","article-title":"The therapeutic potential of curcumin: A review of clinical trials","volume":"163","author":"Salehi","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/1475-2891-11-79","article-title":"Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people","volume":"11","author":"DiSilvestro","year":"2012","journal-title":"Nutr. J."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Di Meo, F., Valentino, A., Petillo, O., Peluso, G., Filosa, S., and Crispi, S. (2020). Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072564"},{"key":"ref_160","first-page":"2272","article-title":"Resveratrol and Neuroprotection: Impact and Its Therapeutic Potential in Alzheimer\u2019s Disease","volume":"30","author":"Rahman","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000454681","article-title":"Effect of Melatonin and Resveratrol against Memory Impairment and Hippocampal Damage in a Rat Model of Vascular Dementia","volume":"23","author":"Shen","year":"2016","journal-title":"Neuroimmunomodulation"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.brainres.2008.02.107","article-title":"Green tea epigallocatechin-3-gallate (EGCG) reduces \u03b2-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice","volume":"1214","author":"Arendash","year":"2008","journal-title":"Brain Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1016\/j.biocel.2010.08.017","article-title":"BACE: Therapeutic target and potential biomarker for Alzheimer\u2019s disease","volume":"42","author":"Evin","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.neuroscience.2016.02.040","article-title":"Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro","volume":"322","author":"Ichwan","year":"2016","journal-title":"Neuroscience"},{"key":"ref_165","first-page":"1237","article-title":"Quercetin enrich diet during the early-middle not middle-late stage of alzheimer\u2019s disease ameliorates cognitive dysfunction","volume":"10","author":"Lu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"67716","DOI":"10.18632\/oncotarget.11963","article-title":"Quercetin ameliorates A\u03b2 toxicity in Drosophila AD model by modulating cell cycle-related protein expression","volume":"7","author":"Kong","year":"2016","journal-title":"Oncotarget"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1159\/000484302","article-title":"Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats with Parkinson\u2019s Disease Through the Wnt\/\u03b2-Catenin Signaling Pathway","volume":"43","author":"Wang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1080\/1028415X.2020.1829344","article-title":"Hydroxytyrosol improves mitochondrial energetics of a cellular model of Alzheimer\u2019s disease","volume":"25","author":"Visioli","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1021\/acs.jafc.7b05063","article-title":"Neuroprotective Effect of Hydroxytyrosol in Experimental Diabetic Retinopathy: Relationship with Cardiovascular Biomarkers","volume":"66","author":"Reyes","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1096\/fj.201902643R","article-title":"Hydroxytyrosol stimulates neurogenesis in aged dentate gyrus by enhancing stem and progenitor cell proliferation and neuron survival","volume":"34","author":"Ceccarelli","year":"2020","journal-title":"FASEB J."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Chiu, H.-F., Venkatakrishnan, K., Golovinskaia, O., and Wang, C.-K. (2021). Gastroprotective Effects of Polyphenols against Various Gastro-Intestinal Disorders: A Mini-Review with Special Focus on Clinical Evidence. Molecules, 26.","DOI":"10.3390\/molecules26072090"},{"key":"ref_173","first-page":"811","article-title":"Resveratrol abrogates adhesion molecules and protects against TNBS-induced ulcerative colitis in rats","volume":"89","author":"Abdallah","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cyto.2013.12.010","article-title":"Involvement of TACE in colon inflammation: A novel mechanism of regulation via SIRT-1 activation","volume":"66","author":"Sharma","year":"2014","journal-title":"Cytokine"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/15384101.2017.1387701","article-title":"Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway","volume":"17","author":"Ju","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"784211","DOI":"10.3389\/fmicb.2021.784211","article-title":"Caffeic Acid Supplement Alleviates Colonic Inflammation and Oxidative Stress Potentially Through Improved Gut Microbiota Community in Mice","volume":"12","author":"Wan","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1002\/mnfr.200800446","article-title":"Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models","volume":"53","author":"Larrosa","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.freeradbiomed.2010.04.013","article-title":"Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis","volume":"49","author":"Pal","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Karthikeyan, A., Young, K., Moniruzzaman, M., Beyene, A., Do, K., Kalaiselvi, S., and Min, T. (2021). Curcumin and Its Modified Formulations on Inflammatory Bowel Disease (IBD): The Story So Far and Future Outlook. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13040484"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/ijfn.2020.9","article-title":"Polyphenols in cancer prevention: New insights (Review)","volume":"1","author":"Briguglio","year":"2020","journal-title":"Int. J. Funct. Nutr."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Reyes-Farias, M., and Carrasco-Pozo, C. (2019). The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133177"},{"key":"ref_182","first-page":"39","article-title":"The effect of caffeic acid phenethyl ester on cell cycle control gene expressions in breast cancer cells","volume":"10","author":"Kayabasi","year":"2021","journal-title":"Mol. Biol. Res. Commun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"717","DOI":"10.3892\/or.2020.7891","article-title":"Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF-\u03baB signaling pathway","volume":"45","author":"Zeng","year":"2021","journal-title":"Oncol. Rep."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"7913","DOI":"10.2147\/CMAR.S253591","article-title":"Effects of Hydroxytyrosol on Expression of Apoptotic Genes and Activity of Antioxidant Enzymes in LS180 Cells","volume":"12","author":"Hormozi","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Wei, R., Hackman, R.M., Wang, Y., and Mackenzie, G.G. (2019). Targeting Glycolysis with Epigallocatechin-3-Gallate Enhances the Efficacy of Chemotherapeutics in Pancreatic Cancer Cells and Xenografts. Cancers, 11.","DOI":"10.3390\/cancers11101496"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"8912961","DOI":"10.1155\/2019\/8912961","article-title":"Curcumin Inhibits ERK\/c-Jun Expressions and Phosphorylation against Endometrial Carcinoma","volume":"2019","author":"Zhang","year":"2019","journal-title":"BioMed. Res. Int."},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Wang, X.-L., Li, T., Li, J.-H., Miao, S.-Y., and Xiao, X.-Z. (2017). The Effects of Resveratrol on Inflammation and Oxidative Stress in a Rat Model of Chronic Obstructive Pulmonary Disease. Molecules, 22.","DOI":"10.3390\/molecules22091529"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Yahfoufi, N., Alsadi, N., Jambi, M., and Matar, C. (2018). The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients, 10.","DOI":"10.3390\/nu10111618"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"612268","DOI":"10.3389\/fphys.2020.612268","article-title":"The Impact of Polyphenols-Based Diet on the Inflammatory Profile in COVID-19 Elderly and Obese Patients","volume":"11","author":"Santos","year":"2021","journal-title":"Front. Physiol."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/12\/3051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:26:56Z","timestamp":1760146016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/12\/3051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,25]]},"references-count":189,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["biomedicines10123051"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10123051","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,25]]}}}