{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:17:28Z","timestamp":1788585448786,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"crossref","award":["2026\u20130026"],"award-info":[{"award-number":["2026\u20130026"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2026\u20130026"],"award-info":[{"award-number":["2026\u20130026"]}],"id":[{"id":"https:\/\/ror.org\/03qjsrb10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Bioactive polyphenols have emerged as multi-target regulators of cellular processes involved in the pathogenesis of skin diseases. Skin disorders, including inflammatory conditions, photoaging, and skin cancers, are characterized by complex pathogenic mechanisms associated with oxidative stress, mitochondrial dysfunction, dysregulated signaling pathways, and metabolic imbalance. Excessive production of reactive oxygen species (ROS) and persistent inflammatory signaling contribute to disease progression and cellular adaptation under stress conditions. Unlike conventional agents that typically target a single pathway, polyphenols act on interconnected signaling and metabolic networks. These compounds regulate key signaling pathways, including phosphoinositide 3-kinase\/protein kinase B (PI3K\/Akt), mitogen-activated protein kinase\/extracellular signal-regulated kinase (MAPK\/ERK), AMP-activated protein kinase (AMPK), nuclear factor-\u03baB (NF-\u03baB), and nuclear factor erythroid 2-related factor 2 (Nrf2), thereby regulating cell survival, proliferation, inflammatory responses, antioxidant defense, and metabolic adaptation. Polyphenols also influence mitochondrial function by maintaining redox homeostasis, regulating energy metabolism, and affecting apoptosis-related signaling pathways. This review provides a mechanistic overview of the effects of polyphenols on oxidative stress, mitochondrial function, and cell survival signaling in skin diseases. In addition, the therapeutic implications and current limitations of polyphenol-based approaches are discussed, with particular emphasis on the translational gap between experimental findings and physiological relevance. Factors such as concentration, bioavailability, and cellular microenvironment are highlighted as major determinants of polyphenol activity and key challenges for clinical translation. Finally, the need for further in vivo and clinical investigations is emphasized to support the development of effective polyphenol-based therapeutic strategies for skin diseases.<\/jats:p>","DOI":"10.3390\/ijms27177877","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"7877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphenols as Multi-Target Regulators of Oxidative Stress, Mitochondrial Function, and Cell Survival Signaling in Skin Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Moon-Kyun","family":"Cho","sequence":"first","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31511, Republic of Korea"},{"name":"Department of Dermatology, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1273-6444","authenticated-orcid":false,"given":"Min Hyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Dam","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-179X","authenticated-orcid":false,"given":"Sukh Que","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Soonchunhyang University Hospital, Seoul 04401, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Han","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31511, Republic of Korea"},{"name":"Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-Seon","family":"Nam","sequence":"additional","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31511, Republic of Korea"},{"name":"Department of Tropical Medicine, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-1284","authenticated-orcid":false,"given":"Yoon-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Molecular Cancer Research, Soonchunhyang Medical Research Institute, Soonchunhyang University, Cheonan 31511, Republic of Korea"},{"name":"Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31511, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1093\/inthealth\/ihaf070","article-title":"Global, regional and national burden of skin and subcutaneous diseases: A systematic analysis of the Global Burden of Disease Study 2021","volume":"18","author":"Li","year":"2026","journal-title":"Int. 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