{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:09:35Z","timestamp":1788772175838,"version":"build-2803163510"},"reference-count":123,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fattoria La Vialla di Gianni, Antonio e Bandino Lo Franco\u2014SAS"},{"name":"Italian Ministry of Health Ricerca Corrente\u2013IRCCS IEO and IRCCS MultiMedica"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Skin health is increasingly recognised as a key determinant of overall well-being, and its decline is driven by multiple interconnected biological processes. Hydroxytyrosol (HT), an olive polyphenol, exhibits pleiotropic biological activities and has a potential role in supporting skin homeostasis. This narrative review critically evaluates the evidence on oral HT and HT-rich olive-derived nutraceuticals for skin health and healthy ageing with a focus on oxidative damage, inflammation, photoprotection, extracellular matrix (ECM) preservation, wound healing, and skin pigmentation conditions. HT exhibits high oral bioavailability and modulates antioxidant defences, inflammatory signalling, autophagy, apoptosis, and metabolic homeostasis. Preclinical studies consistently show protective effects against oxidative stress, ECM degradation, cellular senescence, photoageing, impaired wound healing, and ultraviolet-induced skin damage. Experimental evidence also indicates antiproliferative and pro-apoptotic effects in melanoma models through modulation of oncogenic signalling pathways, suggesting a potential role in skin cancer prevention. In vivo, oral HT administration improves glycative skin ageing, psoriasis, intestinal barrier integrity, and systemic inflammation. Clinical evidence supports systemic antioxidant and cardiometabolic benefits of purified HT and HT-rich formulations, while dermatological evidence remains preliminary for psoriasis, melasma, and wound healing. Overall, HT shows promise, but randomised controlled trials with validated dermatological endpoints are needed to confirm its clinical efficacy.<\/jats:p>","DOI":"10.3390\/antiox15091095","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:21:19Z","timestamp":1788168079000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydroxytyrosol and Olive-Derived Hydroxytyrosol-Rich Products for Skin Health and Prevention of Skin Ageing: Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-5103","authenticated-orcid":false,"given":"Adriana","family":"Albini","sequence":"first","affiliation":[{"name":"Scientific Directorate, European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Morelli","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-9823","authenticated-orcid":false,"given":"Cecilia","family":"Bender","sequence":"additional","affiliation":[{"name":"Institut Kurz GmbH, Nattermannallee 1, 50829 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1448-9517","authenticated-orcid":false,"given":"Paola","family":"Corradino","sequence":"additional","affiliation":[{"name":"European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.2147\/CCID.S539786","article-title":"Skin Care Supports Overall Well-Being","volume":"18","author":"Zhu","year":"2025","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-319-56017-5_7","article-title":"Ultraviolet Radiations: Skin Defence-Damage Mechanism","volume":"996","author":"Mohania","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119316","DOI":"10.1016\/j.envpol.2022.119316","article-title":"Human Skin Responses to Environmental Pollutants: A Review of Current Scientific Models","volume":"306","author":"Fitoussi","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11882-008-0048-0","article-title":"Skin Barrier Function","volume":"8","author":"Elias","year":"2008","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jiang, N., Quan, T., Li, R., Chen, Y., and Gao, T. (2025). Role of Nutritional Elements in Skin Homeostasis: A Review. Biomolecules, 15.","DOI":"10.3390\/biom15060808"},{"key":"ref_6","first-page":"5551","article-title":"Ageing-Associated Alterations in Epidermal Function and Their Clinical Significance","volume":"12","author":"Wang","year":"2020","journal-title":"Ageing"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.jid.2017.01.007","article-title":"Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines","volume":"137","author":"Hu","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3390\/biom5020545","article-title":"Oxidative Stress in Aging Human Skin","volume":"5","author":"Rinnerthaler","year":"2015","journal-title":"Biomolecules"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.arr.2015.01.001","article-title":"Oxidation Events and Skin Ageing","volume":"21","author":"Kammeyer","year":"2015","journal-title":"Ageing Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000322643","article-title":"Antioxidant Therapies for Wound Healing: A Clinical Guide to Currently Commercially Available Products","volume":"24","author":"Fitzmaurice","year":"2011","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2165\/00128071-200304060-00001","article-title":"Skin Aging and Menopause: Implications for Treatment","volume":"4","author":"Brincat","year":"2003","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41435-021-00133-9","article-title":"Mechanisms of Microbe-Immune System Dialogue Within the Skin","volume":"22","author":"Lunjani","year":"2021","journal-title":"Genes Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102518","DOI":"10.1016\/j.arr.2024.102518","article-title":"Biotics as Novel Therapeutics in Targeting Signs of Skin Ageing via the Gut-Skin Axis","volume":"102","author":"Millman","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2473524","DOI":"10.1080\/19490976.2025.2473524","article-title":"The Gut-Skin Axis: A Bi-Directional, Microbiota-Driven Relationship With Therapeutic Potential","volume":"17","author":"Celiberto","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"D\u2019Angelo, C., Franceschelli, S., Quiles, J.L., and Speranza, L. (2020). Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases. Cells, 9.","DOI":"10.3390\/cells9091932"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Echeverr\u00eda, F., Ortiz, M., Valenzuela, R., and Videla, L.A. (2017). Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18050930"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jord\u00e1n, M., Garc\u00eda-Acosta, N., Espartero, J.L., Goya, L., and Mateos, R. (2025). Hydroxytyrosol Bioavailability: Unraveling Influencing Factors and Optimization Strategies for Dietary Supplements. Nutrients, 17.","DOI":"10.3390\/nu17182937"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13065-016-0207-7","article-title":"Quick Assessment of the Economic Value of Olive Mill Waste Water","volume":"10","author":"Delisi","year":"2016","journal-title":"Chem. Cent. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s00253-014-6310-6","article-title":"The Antioxidant Hydroxytyrosol: Biotechnological Production Challenges and Opportunities","volume":"99","author":"Achmon","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.7150\/ijbs.97263","article-title":"The PI3K\/Akt-Nrf2 Signalling Pathway and Mitophagy Synergistically Mediate Hydroxytyrosol to Alleviate Intestinal Oxidative Damage","volume":"20","author":"Wen","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1177\/0960327120949618","article-title":"Hydroxytyrosol Ameliorates Oxidative Challenge and Inflammatory Response Associated with Lipopolysaccharide-mediated Sepsis in Mice","volume":"40","author":"Alblihed","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1248\/bpb.b18-00979","article-title":"Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats","volume":"42","author":"Yonezawa","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fuccelli, R., Fabiani, R., and Rosignoli, P. (2018). Hydroxytyrosol Exerts Anti-Inflammatory and Anti-Oxidant Activities in a Mouse Model of Systemic Inflammation. Molecules, 23.","DOI":"10.3390\/molecules23123212"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/mnfr.200900159","article-title":"Hydroxytyrosol Induces Antioxidant\/Detoxificant Enzymes and Nrf2 Translocation via Extracellular Regulated Kinases and Phosphatidylinositol-3-kinase\/protein Kinase B Pathways in HepG2 Cells","volume":"54","author":"Ramos","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101516","DOI":"10.1016\/j.psj.2021.101516","article-title":"Immunomodulatory and Antioxidant Effects of Hydroxytyrosol in Cyclophosphamide-Induced Immunosuppressed Broilers","volume":"101","author":"Shan","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xu, J., Wei, H., Sun, Z., Li, W., Long, J., Liu, J., Feng, Z., and Cao, K. (2025). Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases. Antioxidants, 14.","DOI":"10.3390\/antiox14040398"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Qian, H., Shan, Y., Gong, R., Lin, D., Zhang, M., Wang, C., and Wang, L. (2023). Mechanism of Action and Therapeutic Effects of Oxidative Stress and Stem Cell-Based Materials in Skin Ageing: Current Evidence and Future Perspectives. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1082403"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Soldevila-Domenech, N., Boronat, A., Mateus, J., Diaz-Pellicer, P., Matilla, I., P\u00e9rez, M., Tresserra-Rimbau, A., P\u00e9rez-Fern\u00e1ndez, S., de la Torre, R., and Lamuela-Ravent\u00f3s, R.M. (2019). Generation of Hydroxytyrosol from Tyrosol in Humans. Nutrients, 11.","DOI":"10.3390\/nu11092241"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"124434","DOI":"10.1016\/j.ijpharm.2024.124434","article-title":"Hydroxytyrosol Permeability Comparisons and Strategies to Improve Hydroxytyrosol Stability in Formulations","volume":"661","author":"Feng","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Frumuzachi, O., P\u0103duraru, O., Khan, F., Mocan, A., and Moldovan, L. (2024). Systemic Health Effects of Oleuropein and Hydroxytyrosol Supplementation: A Systematic Review of Randomised Controlled Trials. Antioxidants, 13.","DOI":"10.3390\/antiox13091040"},{"key":"ref_31","first-page":"17","article-title":"Hydroxytyrosol Supplementation Modulates Metabolic and Cardiovascular Risk Factors in Over-Weight\/Obese Prediabetic Subjects: A Randomised, Double-Blind, Placebo-Controlled Clinical Trial","volume":"52","author":"Marhuenda","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2473495","DOI":"10.1155\/2017\/2473495","article-title":"Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomised, Double-Blinded, Placebo-Controlled Crossover Trial","volume":"2017","author":"Colica","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.2147\/CIA.S430552","article-title":"Improvement in Cutaneous Conditions Can Benefit Some Health Conditions in the Elderly","volume":"18","author":"Yang","year":"2023","journal-title":"Clin. Interv. Aging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jdermsci.2016.09.015","article-title":"The Skin Ageing Exposome","volume":"85","author":"Krutmann","year":"2017","journal-title":"J. Dermatol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"a015370","DOI":"10.1101\/cshperspect.a015370","article-title":"Natural and Sun-Induced Ageing of Human Skin","volume":"5","author":"Fisher","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1177\/0963689717725755","article-title":"Fighting against Skin Ageing: The Way from Bench to Bedside","volume":"27","author":"Zhang","year":"2018","journal-title":"Cell Transplant."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"tkad059","DOI":"10.1093\/burnst\/tkad059","article-title":"The Role of the Skin Microbiome in Wound Healing","volume":"12","author":"Yang","year":"2024","journal-title":"Burn. Trauma"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e70393","DOI":"10.1111\/jocd.70393","article-title":"Managing Menopausal Skin Changes: A Narrative Review of Skin Quality Changes, Their Aesthetic Impact, and the Actual Role of Hormone Replacement Therapy in Improvement","volume":"24","author":"Viscomi","year":"2025","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1038\/jid.2010.204","article-title":"Airborne Particle Exposure and Extrinsic Skin Ageing","volume":"130","author":"Schikowski","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Agrawal, R., Hu, A., and Bollag, W.B. (2023). The Skin and Inflamm-Ageing. Biology, 12.","DOI":"10.3390\/biology12111396"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1016\/j.jid.2024.09.025","article-title":"The Role and Implications of Epidermal Dysfunction in the Pathogenesis of Inflammageing","volume":"145","author":"Zhang","year":"2025","journal-title":"J. Investig. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1600-0625.2010.01242.x","article-title":"The Role of Telomeres in the Ageing of Human Skin","volume":"20","author":"Buckingham","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"He, X., Gao, X., and Xie, W. (2024). Research Progress in Skin Ageing and Immunity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25074101"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1073\/pnas.1901720117","article-title":"The Ageing Skin Microenvironment Dictates Stem Cell Behavior","volume":"117","author":"Ge","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dobric\u0103, E.C., Cozma, M., G\u0103man, M.A., Voiculescu, V.M., and G\u0103man, A.M. (2022). The Involvement of Oxidative Stress in Psoriasis: A Systematic Review. Antioxidants, 11.","DOI":"10.3390\/antiox11020282"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1056\/NEJM199904293401707","article-title":"The Pathogenesis of Melanoma Induced by Ultraviolet Radiation","volume":"340","author":"Gilchrest","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/j.1365-2133.2007.08108.x","article-title":"Photoageing: Mechanism, Prevention and Therapy","volume":"157","author":"Yaar","year":"2007","journal-title":"Br. J. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1467-2494.2004.00241.x","article-title":"Ultraviolet Radiation and Skin Ageing: Roles of Reactive Oxygen Species, Inflammation and Protease Activation","volume":"27","author":"Pillai","year":"2005","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1159\/000371708","article-title":"Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Ageing","volume":"61","author":"Quan","year":"2015","journal-title":"Gerontology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s001250051591","article-title":"Advanced Glycation End-Products: A Review","volume":"44","author":"Singh","year":"2001","journal-title":"Diabetologia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.foodchem.2015.06.049","article-title":"Analysis of Advanced Glycation Endproducts in Selected Food Items by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry: Presentation of a Dietary AGE Database","volume":"190","author":"Scheijen","year":"2016","journal-title":"Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fan, R., Ma, Y., Sun, M., Zhang, H., Han, Y., Wang, J., Zhu, W., and Zhang, Z. (2025). Improvement Effect and Mechanism of Hydroxytyrosol on Skin Ageing Induced Advanced Glycation End Products. Nutrients, 17.","DOI":"10.3390\/nu17172810"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4161\/derm.22028","article-title":"Advanced Glycation End Products: Key Players in Skin Ageing?","volume":"4","author":"Gkogkolou","year":"2012","journal-title":"Derm.-Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, C.Y., Zhang, J.Q., Li, L., Guo, M.M., He, Y.F., Dong, Y.M., Meng, H., and Yi, F. (2022). Advanced Glycation End Products in the Skin: Molecular Mechanisms, Methods of Measurement, and Inhibitory Pathways. Front. Med., 9.","DOI":"10.3389\/fmed.2022.837222"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/1547691X.2021.1959677","article-title":"Dietary Advanced Glycation End-Products Elicit Toxicological Effects by Disrupting Gut Microbiome and Immune Homeostasis","volume":"18","author":"Chen","year":"2021","journal-title":"J. Immunotoxicol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Twarda-Clapa, A., Olczak, A., Bia\u0142kowska, A.M., and Kozio\u0142kiewicz, M. (2022). Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs. Cells, 11.","DOI":"10.3390\/cells11081312"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chrysanthou, M., Miro Estruch, I., Rietjens, I.M.C.M., Wichers, H.J., and Hoppenbrouwers, T. (2022). In Vitro Methodologies to Study the Role of Advanced Glycation End Products (AGEs) in Neurodegeneration. Nutrients, 14.","DOI":"10.3390\/nu14020363"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.2337\/db16-0397","article-title":"Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules","volume":"66","author":"Takahashi","year":"2017","journal-title":"Diabetes"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"G\u00f3mez, O., Perini-Villanueva, G., Yuste, A., Rodr\u00edguez-Navarro, J.A., Poch, E., and Bejarano, E. (2021). Autophagy and Glycative Stress: A Bittersweet Relationship in Neurodegeneration. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.790479"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/jdv.16453","article-title":"Autophagy Activators Stimulate the Removal of Advanced Glycation End Products in Human Keratinocytes","volume":"34","author":"Laughlin","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ple\u0144kowska, J., Gabig-Cimi\u0144ska, M., and Mozolewski, P. (2020). Oxidative Stress as an Important Contributor to the Pathogenesis of Psoriasis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176206"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ni, Q., Zhang, P., Li, Q., and Han, Z. (2022). Oxidative Stress and Gut Microbiome in Inflammatory Skin Diseases. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.849985"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1007\/s13555-026-01732-y","article-title":"Integrative Dermatology for Longevity: The Synergy of Topical and Internal Approaches","volume":"16","author":"Haykal","year":"2026","journal-title":"Dermatol. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Nisar, A., Jagtap, S., Vyavahare, S., Deshpande, M., Harsulkar, A., Ranjekar, P., and Prakash, O. (2023). Phytochemicals in the Treatment of Inflammation-Associated Diseases: The Journey from Preclinical Trials to Clinical Practice. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1177050"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chaiprasongsuk, A., and Panich, U. (2022). Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.823881"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Assaf, S., and Kelly, O. (2025). Nutritional Dermatology: Optimizing Dietary Choices for Skin Health. Nutrients, 17.","DOI":"10.3390\/nu17010060"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Albini, A., Corradino, P., Morelli, D., Albini, F., and Noonan, D. (2025). Cosmeceutical and Dermatological Potential of Olive Mill Wastewater: A Sustainable and Eco-Friendly Source of Natural Ingredients. Cosmetics, 12.","DOI":"10.3390\/cosmetics12040142"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1039\/C7FO00641A","article-title":"Tyrosol and Its Metabolites as Antioxidative and Anti-Inflammatory Molecules in Human Endothelial Cells","volume":"8","author":"Muriana","year":"2017","journal-title":"Food Funct."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Silva, A.F.R., Resende, D., Monteiro, M., Coimbra, M.A., Silva, A.M.S., and Cardoso, S.M. (2020). Application of Hydroxytyrosol in the Functional Foods Field: From Ingredient to Dietary Supplements. Antioxidants, 9.","DOI":"10.3390\/antiox9121246"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Di Renzo, L., Smeriglio, A., Ingegneri, M., Gualtieri, P., and Trombetta, D. (2023). The Pharmaceutical Formulation Plays a Pivotal Role in Hydroxytyrosol Pharmacokinetics. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030743"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"118578","DOI":"10.1016\/j.foodres.2026.118578","article-title":"Does Hydroxytyrosol Deserve a Health Claim? Effects of Its Supplementation on Ageing Mechanism from Preclinical to Human Intervention Studies","volume":"231","author":"Mateos","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Gao, Y., Liu, W., Pan, S., Li, J., Wang, J., Chen, L., Ma, X., and Leng, H. (2025). Hydroxytyrosol: Biological Activities and Potential Application in Livestock Production. Front. Vet. Sci., 12.","DOI":"10.3389\/fvets.2025.1632596"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2015.06.021","article-title":"Mechanisms of Activation of the Transcription Factor Nrf2 by Redox Stressors, Nutrient Cues, and Energy Status and the Pathways Through Which It Attenuates Degenerative Disease","volume":"88","author":"Tebay","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5036572","DOI":"10.1155\/2020\/5036572","article-title":"Hydroxytyrosol Plays Antiatherosclerotic Effects through Regulating Lipid Metabolism via Inhibiting the p38 Signal Pathway","volume":"2020","author":"Zhang","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_75","first-page":"6455","article-title":"Hydroxytyrosol Suppresses LPS-Induced Intrahepatic Inflammatory Responses via Inhibition of ERK Signalling Pathway Activation in Acute Liver Injury","volume":"24","author":"Yu","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/oby.20239","article-title":"Effect of the Mediterranean Diet with and Without Weight Loss on Markers of Inflammation in Men with Metabolic Syndrome","volume":"21","author":"Richard","year":"2013","journal-title":"Obesity"},{"key":"ref_77","first-page":"1531","article-title":"Hydroxytyrosol Promotes Autophagy by Regulating SIRT1 Against Advanced Oxidation Protein Product-Induced NADPH Oxidase and Inflammatory Response","volume":"44","author":"Sun","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e12963","DOI":"10.1016\/j.heliyon.2023.e12963","article-title":"Hydroxytyrosol: Its Role in the Prevention of Cardiovascular Diseases","volume":"9","year":"2023","journal-title":"Heliyon"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Wang, Z., Lei, Z., Zhang, H., Liu, Z., Chen, W., Jia, Y., Shi, R., and Wang, C. (2025). From Biosynthesis to Legislation: A Review of Hydroxytyrosol\u2019s Biological Functions and Safety. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104470"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Covas, M.I., Fit\u00f3, M., and de la Torre, R. (2015). Minor Bioactive Olive Oil Components and Health: Key Data for Their Role in Providing Health Benefits in Humans. Olive and Olive Oil Bioactive Constituents, AOCS Press.","DOI":"10.1016\/B978-1-63067-041-2.50008-2"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sciubba, F., Chronopoulou, L., Pizzichini, D., Lionetti, V., Fontana, C., Aromolo, R., Socciarelli, S., Gambelli, L., Bartolacci, B., and Finotti, E. (2020). Olive Mill Wastes: A Source of Bioactive Molecules for Plant Growth and Protection against Pathogens. Biology, 9.","DOI":"10.3390\/biology9120450"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Albini, A., Albini, F., Corradino, P., Dugo, L., Calabrone, L., and Noonan, D.M. (2023). From Antiquity to Contemporary Times: How Olive Oil By-Products and Waste Water Can Contribute to Health. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1254947"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Cuffaro, D., Bertolini, A., Bertini, S., Ricci, C., Cascone, M.G., Danti, S., Saba, A., Macchia, M., and Digiacomo, M. (2023). Olive Mill Wastewater as Source of Polyphenols with Nutraceutical Properties. Nutrients, 15.","DOI":"10.3390\/nu15173746"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Morelli, D., Nofri, S., Corradino, P., Pellegrini-Giampietro, D.E., Caruso, C., Aiello, A., and Albini, A. (2026). A Polyphenol-Rich Olive Oil Byproduct-Derived Nutraceutical Preserves Muscle Health in Adults at Metabolic Risk: A Secondary Analysis of a Pilot Study. Nutrients, 18.","DOI":"10.3390\/nu18101551"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Bender, C., Stra\u00dfmann, S., and Heidrich, P. (2021). Cellular Antioxidant Effects and Bioavailability of Food Supplements Rich in Hydroxytyrosol. Appl. Sci., 11.","DOI":"10.3390\/app11114763"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Roberts, J.D., Lillis, J., Pinto, J.M., Willmott, A.G.B., Gautam, L., Davies, C., L\u00f3pez-Samanes, \u00c1., Del Coso, J., and Chichger, H. (2022). The Impact of a Natural Olive-Derived Phytocomplex (OliPhenolia\u00ae) on Exercise-Induced Oxidative Stress in Healthy Adults. Nutrients, 14.","DOI":"10.3390\/nu14235156"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Bender, C., Strassmann, S., and Golz, C. (2023). Oral Bioavailability and Metabolism of Hydroxytyrosol from Food Supplements. Nutrients, 15.","DOI":"10.3390\/nu15020325"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Bender, C., Candi, I., and Rogel, E. (2023). Efficacy of Hydroxytyrosol-Rich Food Supplements on Reducing Lipid Oxidation in Humans. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065521"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0891-5849(99)00264-6","article-title":"Measurement of F(2)-Isoprostanes as an Index of Oxidative Stress In Vivo","volume":"28","author":"Roberts","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-61779-170-3_13","article-title":"Measurement of Isoprostanes as Markers of Oxidative Stress","volume":"758","author":"Milatovic","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Aiello, A., Calabrone, L., Noonan, D.M., Corradino, P., Nofri, S., Cristoni, S., Accardi, G., Candore, G., Caruso, C., and Zinellu, A. (2024). Effect of a Phytochemical-Rich Olive-Derived Extract on Anthropometric, Hematological, and Metabolic Parameters. Nutrients, 16.","DOI":"10.20944\/preprints202408.0102.v1"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1007\/s00394-023-03133-9","article-title":"Positive Contribution of Hydroxytyrosol-Enriched Wheat Bread to HbA1c Levels, Lipid Profile, Markers of Inflammation and Body Weight in Subjects with Overweight\/Obesity and Type 2 Diabetes Mellitus","volume":"62","author":"Binou","year":"2023","journal-title":"Eur. J. Nutr."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zoubdane, N., Abdo, R.A., Nguyen, M., Bentourkia, M., Turcotte, E.E., Berrougui, H., Fulop, T., and Khalil, A. (2024). High Tyrosol and Hydroxytyrosol Intake Reduces Arterial Inflammation and Atherosclerotic Lesion Microcalcification in Healthy Older Populations. Antioxidants, 13.","DOI":"10.20944\/preprints202401.0357.v1"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e1900019","DOI":"10.1002\/mnfr.201900019","article-title":"Olive-Oil-Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF-\u03baB Pathway","volume":"63","author":"Redhu","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s41702-018-0031-x","article-title":"Anti-Inflammatory and Anti-Ageing Effects of Hydroxytyrosol on Human Dermal Fibroblasts (HDFs)","volume":"2","author":"Jeon","year":"2018","journal-title":"Biomed. Dermatol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Menicacci, B., Cipriani, C., Margheri, F., Mocali, A., and Giovannelli, L. (2017). Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112275"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11509","DOI":"10.1021\/jf300883h","article-title":"Novel, biocatalytically produced hydroxytyrosol dimer protects against ultraviolet-induced cell death in human immortalized keratinocytes","volume":"60","author":"Zwane","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Batarfi, W.A., Mohd Yunus, M.H., and Hamid, A.A. (2023). Hydroxytyrosol in Epithelial-Mesenchymal Transition during Wound Healing. Molecules, 28.","DOI":"10.3390\/molecules28062652"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Acedo, A., Ramos-Torrecillas, J., Illescas-Montes, R., Costela-Ruiz, V.J., Ruiz, C., Melguizo-Rodr\u00edguez, L., and Garc\u00eda-Mart\u00ednez, O. (2023). The Benefits of Olive Oil for Skin Health: Study on the Effect of Hydroxytyrosol, Tyrosol, and Oleocanthal on Human Fibroblasts. Nutrients, 15.","DOI":"10.3390\/nu15092077"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/ptr.5339","article-title":"Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 De Novo Synthesis and Stabilization","volume":"29","author":"Zrelli","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40199-019-00274-3","article-title":"Safety and Efficacy of Hydroxytyrosol-Based Formulation on Skin Inflammation: In Vitro Evaluation on Reconstructed Human Epidermis Model","volume":"27","author":"Smeriglio","year":"2019","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1080\/09637486.2021.1996542","article-title":"Dietary Polyphenol Oleuropein and Its Metabolite Hydroxytyrosol Are Moderate Skin Permeable Elastase and Collagenase Inhibitors with Synergistic Cellular Antioxidant Effects in Human Skin Fibroblasts","volume":"73","author":"Li","year":"2022","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1080\/08923973.2022.2143373","article-title":"Anti-Psoriasis Activities of Hydroxytyrosol on HaCaT Cells Under Psoriatic Inflammation In Vitro","volume":"45","author":"Chen","year":"2023","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"30125","DOI":"10.1038\/s41598-025-16198-9","article-title":"Hydroxytyrosol Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis by Modulating ERK and NF-\u03baB Signalling Pathways in Mice","volume":"15","author":"Liu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/wrr.13217","article-title":"Polyphenol Hydroxytyrosol Present Olive Oil Improves Skin Wound Healing of Diabetic Mice","volume":"32","author":"Duarte","year":"2024","journal-title":"Wound Repair Regen."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phanu.2016.10.002","article-title":"An Olive Polyphenol-Based Nutraceutical Improves Cutaneous Manifestations of Psoriasis in Humans","volume":"4","author":"Acosta","year":"2016","journal-title":"PharmaNutrition"},{"key":"ref_107","first-page":"48","article-title":"A Pilot Clinical Study to Evaluate the Effectiveness of Olive Extract Containing Hydroxytyrosol for Oral and Topical Treatment of Melasma","volume":"17","author":"Bagatin","year":"2020","journal-title":"Biomed. Biopharm. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13008-024-00107-z","article-title":"Role of Reactive Oxygen Species in Ultraviolet-Induced Photodamage of the Skin","volume":"19","author":"Wei","year":"2024","journal-title":"Cell Div."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/ptr.2943","article-title":"The Protective Effects of Hydroxytyrosol Against UVB-Induced DNA Damage in HaCaT Cells","volume":"24","author":"Guo","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s43094-024-00700-7","article-title":"Hydroxytyrosol in Cancer Research: Recent and Historical Insights on Discoveries and Mechanisms of Action","volume":"10","author":"Kumar","year":"2024","journal-title":"Future J. Pharm. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"41008","DOI":"10.1038\/s41598-025-24845-4","article-title":"Combined Protection Against UVB-Induced Photoageing by Oleuropein, Hydroxytyrosol, and Verbascoside Through Modulation of Inflammation, Oxidative Stress, and Collagen Homeostasis","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1002\/ptr.70387","article-title":"Hydroxytyrosol Improves UV-Induced Skin Photoageing via PI3K-AKT\/MAPK\/JAK-STAT and NF-\u03baB Pathways: Insights From Keratinocytes and In Vivo Validation","volume":"40","author":"Wang","year":"2026","journal-title":"Phytother. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.freeradbiomed.2004.12.015","article-title":"Hydroxytyrosol, a Natural Antioxidant From Olive Oil, Prevents Protein Damage Induced by Long-Wave Ultraviolet Radiation in Melanoma Cells","volume":"38","author":"Ingrosso","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Schlupp, P., Schmidts, T.M., P\u00f6ssl, A., Wildenhain, S., Lo Franco, G., Lo Franco, A., and Lo Franco, B. (2019). Effects of a Phenol-Enriched Purified Extract from Olive Mill Wastewater on Skin Cells. Cosmetics, 6.","DOI":"10.3390\/cosmetics6020030"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Costantini, F., Di Sano, C., and Barbieri, G. (2020). The Hydroxytyrosol Induces the Death for Apoptosis of Human Melanoma Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218074"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Brito, C., Tom\u00e1s, A., Silva, S., Bronze, M.R., Serra, A.T., and Pojo, M. (2021). The Impact of Olive Oil Compounds on the Metabolic Reprogramming of Cutaneous Melanoma Cell Models. Molecules, 26.","DOI":"10.3390\/molecules26020289"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Tovar-Parra, D., and Mangion, M.Z. (2025). Hydroxytyrosol Reprograms the Tumor Microenvironment in 3D Melanoma Models by Suppressing ERBB Family and Kinase Pathways. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146957"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Gervasi, F., and Pojero, F. (2024). Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine. Biomedicines, 12.","DOI":"10.3390\/biomedicines12030502"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Boss, A., Bishop, K.S., Marlow, G., Barnett, M.P., and Ferguson, L.R. (2016). Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions. Nutrients, 8.","DOI":"10.3390\/nu8080513"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Imperatrice, M., Lasfar, A., van Kalkeren, C.A.J., and Troost, F. (2024). Olive Leaf Extract Supplementation Improves Postmenopausal Symptoms: A Randomised, Double-Blind, Placebo-Controlled Parallel Study on Postmenopausal Women. Nutrients, 16.","DOI":"10.3390\/nu16223879"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e202401714","DOI":"10.1002\/cbdv.202401714","article-title":"New Insights Into the Antibacterial Activity of Hydroxytyrosol Extracted From Olive Leaves: Molecular Docking Simulations of Its Antibacterial Mechanisms","volume":"22","author":"Abidi","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/5584_2015_5013","article-title":"Antioxidant Hydroxytyrosol-Based Polyacrylate with Antimicrobial and Antiadhesive Activity Versus Staphylococcus epidermidis","volume":"901","author":"Crisante","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1080\/14786419.2017.1356830","article-title":"Antibacterial Activity of Hydroxytyrosol Acetate From Olive Leaves (Olea europaea L.)","volume":"32","author":"Wei","year":"2018","journal-title":"Nat. Prod. Res."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1095\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:31:07Z","timestamp":1788769867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/9\/1095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":123,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["antiox15091095"],"URL":"https:\/\/doi.org\/10.3390\/antiox15091095","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]}}}