{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:38:45Z","timestamp":1772649525412,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Project of Natural Science Foundation by the Science and Technology Bureau of Xiamen","award":["3502Z202374040"],"award-info":[{"award-number":["3502Z202374040"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2024J011395"],"award-info":[{"award-number":["2024J011395"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Taxifolin, a natural flavonoid, consistently exerts cytoprotective effects against various oxidative stresses. In this study, we systematically evaluated its photoprotective efficacy and underlying mechanisms against ultraviolet B (UVB)-induced injury in human immortalized keratinocytes (HaCaT). Cell viability and apoptosis were assessed by MTT, fluorescence staining, and flow cytometry, while integrative transcriptomic and proteomic analyses were employed to identify core pathways and key mediators. Taxifolin exhibited antioxidant capacity comparable to that of ascorbic acid under identical in vitro radical-scavenging assays. Moreover, it displayed a strong absorption peak at 289 nm that overlaps the UVB spectrum (280\u2013320 nm), enabling it to act as a chemical sunscreen. In UVB-challenged HaCaT cells, taxifolin markedly reduced intracellular reactive oxygen species (ROS) and attenuated JNK\/p38 MAPK activation, as evidenced by Western blot, thereby breaking the ROS-MAPK vicious cycle. Multi-omics revealed that taxifolin was associated with attenuation of UVB-imposed G1\/S arrest concomitant with restored Cyclin expression, while up-regulating MYC, FOXQ1, HMOX1 and AP-1 components c-Jun\/c-Fos and thereby switching on a pro-survival transcriptional program. Consequently, apoptosis was suppressed and survival was significantly improved. Collectively, taxifolin integrated chemical filtration, ROS scavenging and signaling modulation to support a multi-target photoprotective network, which provides mechanistic insight into taxifolin-mediated cytoprotection and identifies candidate molecular nodes for further validation.<\/jats:p>","DOI":"10.3390\/biom16030387","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:17:31Z","timestamp":1772641051000},"page":"387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Target Photoprotection by Taxifolin Against UVB-Induced Keratinocyte Injury Through UVB Filtration, ROS Scavenging and Transcriptomic-Proteomic Reprogramming"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-7200","authenticated-orcid":false,"given":"Fangfang","family":"Chen","sequence":"first","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"},{"name":"Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihan","family":"Cai","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxiong","family":"Wu","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nengzhen","family":"Fang","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7562-2026","authenticated-orcid":false,"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"},{"name":"Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongtan","family":"Wu","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"},{"name":"Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-5756","authenticated-orcid":false,"given":"Yu-Pei","family":"Chen","sequence":"additional","affiliation":[{"name":"The School of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"},{"name":"Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/php.12668","article-title":"The cartography of UV-induced DNA damage formation and DNA repair","volume":"93","author":"Hu","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6414","DOI":"10.3390\/ijms14036414","article-title":"Molecular mechanisms of UV-induced apoptosis and its effects on skin residential cells: The implication in UV-based phototherapy","volume":"14","author":"Lee","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117346","DOI":"10.1016\/j.biopha.2024.117346","article-title":"Enhancing ocular protection against UVB: The role of irigenin in modulating oxidative stress and apoptotic pathways In Vivo","volume":"179","author":"Yeh","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1080\/13880209.2025.2583837","article-title":"Cedrol prevents UVB-induced photoaging by restoring mitochondrial function, metabolic homeostasis, and skin barrier integrity in HaCaT cells","volume":"63","author":"Xu","year":"2025","journal-title":"Pharm. Biol."},{"key":"ref_5","first-page":"e04682","article-title":"Scientific Opinion on taxifolin-rich extract from Dahurian Larch (Larix gmelinii)","volume":"15","author":"Turck","year":"2017","journal-title":"EFSA J."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sim, H.H., Ko, J.Y., Gong, D.S., Kim, D.W., Kim, J.J., Lim, H.K., Kim, H.J., and Oak, M.H. (2025). Exploring the protective effects of taxifolin in cardiovascular health: A comprehensive review. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202507.2100.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s11658-017-0066-9","article-title":"The mechanism of (+) taxifolin\u2019s protective antioxidant effect for \u2022OH-treated bone marrow-derived mesenchymal stem cells","volume":"22","author":"Li","year":"2017","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"674","DOI":"10.3109\/14756366.2015.1057723","article-title":"Antioxidant activity of taxifolin: An activity-structure relationship","volume":"31","author":"Topal","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155199","DOI":"10.1016\/j.phymed.2023.155199","article-title":"Taxifolin inhibits melanoma proliferation\/migration impeding USP18\/Rac1\/JNK\/\u03b2-catenin oncogenic signaling","volume":"123","author":"Xu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112517","DOI":"10.1016\/j.intimp.2024.112517","article-title":"Promotion of apoptosis in melanoma cells by taxifolin through the PI3K\/AKT signaling pathway: Screening of natural products using WGCNA and CMAP platforms","volume":"138","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"177100","DOI":"10.1016\/j.ejphar.2024.177100","article-title":"Taxifolin attenuates hepatic ischemia-reperfusion injury by enhancing PINK1\/Parkin-mediated mitophagy","volume":"985","author":"Zhang","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","first-page":"2617","article-title":"A study on the role of Taxifolin in inducing apoptosis of pancreatic cancer cells: Screening results using weighted gene co-expression network analysis","volume":"16","author":"Chen","year":"2024","journal-title":"Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ptr.8031","article-title":"Taxifolin-mediated Nrf2 activation ameliorates oxidative stress and apoptosis for the treatment of glucocorticoid-induced osteonecrosis of the femoral head","volume":"38","author":"Jiang","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s12012-025-09962-w","article-title":"Taxifolin protects against 5-fluorouracil-induced cardiotoxicity in mice through mitigating oxidative stress, inflammation, and apoptosis: Possible involvement of Sirt1\/Nrf2\/HO-1 signaling","volume":"25","author":"Abukhalil","year":"2025","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e70129","DOI":"10.1002\/mnfr.70129","article-title":"Taxifolin inhibits platelet activation and thrombosis by regulating the PI3K\/Akt and MAPK signaling pathways","volume":"69","author":"Guo","year":"2025","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.freeradbiomed.2025.09.015","article-title":"Taxifolin modulates diabetic neuropathy and inhibits insulin fibrillation: A dual mechanistic insight","volume":"241","author":"Imam","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","first-page":"520","article-title":"Taxifolin protects RPE cells against oxidative stress-induced apoptosis","volume":"23","author":"Xie","year":"2017","journal-title":"Mol. Vis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s43630-021-00140-9","article-title":"Effect of the flavonoids quercetin and taxifolin on UVA-induced damage to human primary skin keratinocytes and fibroblasts","volume":"21","author":"Vrba","year":"2022","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1158\/1940-6207.CAPR-11-0397","article-title":"Taxifolin suppresses UV-induced skin carcinogenesis by targeting EGFR and PI3K","volume":"5","author":"Oi","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkae1011","article-title":"The PRIDE database at 20 years: 2025 update","volume":"53","author":"Bandla","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1038\/sj.onc.1205239","article-title":"Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20","volume":"21","author":"She","year":"2002","journal-title":"Oncogene"},{"key":"ref_22","first-page":"554","article-title":"Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis","volume":"14","author":"Zhang","year":"2022","journal-title":"Chin. Herb. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s13197-017-2573-0","article-title":"Antioxidant and iron-chelating properties of taxifolin and its condensation product with glyoxylic acid","volume":"54","author":"Shubina","year":"2017","journal-title":"J. Food Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fagundes, R., and Teixeira, L.K. (2021). Cyclin E\/CDK2: DNA replication, replication stress and genomic instability. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.774845"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13287-020-1580-7","article-title":"Exosomal microRNA-144 from bone marrow-derived mesenchymal stem cells inhibits the progression of non-small cell lung cancer by targeting CCNE1 and CCNE2","volume":"11","author":"Liang","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s13046-018-0829-9","article-title":"Motor neuron and pancreas homeobox 1\/HLXB9 promotes sustained proliferation in bladder cancer by upregulating CCNE1\/2","volume":"37","author":"Chen","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"148957","DOI":"10.1016\/j.ijbiomac.2025.148957","article-title":"The dual role of cyclin D1: Unraveling its tumor-promoting mechanisms and opportunities for therapeutics","volume":"333","author":"Taheri","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nirala, B.K., and Yustein, J.T. (2025). The role of MYC in tumor immune microenvironment regulation: Insights and future directions. Front. Biosci., 30.","DOI":"10.31083\/FBL37304"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.bbagrm.2014.03.013","article-title":"Myc and cell cycle control","volume":"1849","author":"Bretones","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"109235","DOI":"10.1016\/j.clim.2023.109235","article-title":"Increased CYR61 expression activates CCND1\/c-Myc pathway to promote nasal epithelial cells proliferation in chronic rhinosinusitis with nasal polyps","volume":"247","author":"Luo","year":"2023","journal-title":"Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kalampounias, G., Androutsopoulou, T., and Katsoris, P. (2025). JUNB and JUND in urological cancers: A literature review. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47090741"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112570","DOI":"10.1016\/j.mce.2025.112570","article-title":"c-Jun regulates postpartum \u03b2-cell apoptosis and survival downstream of prolactin signaling","volume":"606","author":"Chung","year":"2025","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/sj.cdd.4401946","article-title":"c-Jun promotes cellular survival by suppression of PTEN","volume":"14","author":"Hettinger","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1365-2184.2007.00444.x","article-title":"Role of c-Fos\/JunD in protecting stress-induced cell death","volume":"40","author":"Zhou","year":"2007","journal-title":"Cell Prolif."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1038\/onc.2008.120","article-title":"Multiple facets of junD gene expression are atypical among AP-1 family members","volume":"27","author":"Hernandez","year":"2008","journal-title":"Oncogene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1111\/j.1365-2826.2008.01734.x","article-title":"Measurement of immediate-early gene activation- c-fos and beyond","volume":"20","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"ref_37","first-page":"209","article-title":"c-Fos expression differentially acts in the healthy brain compared with Alzheimer\u2019s disease","volume":"24","author":"Babaei","year":"2025","journal-title":"J. Gene Expr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1038\/ncb0502-e131","article-title":"AP-1 as a regulator of cell life and death","volume":"4","author":"Shaulian","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.3748\/wjg.14.6339","article-title":"c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1","volume":"14","author":"Legrand","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.neuint.2009.04.003","article-title":"Bcl-2 or bcl-XL gene therapy increases neural plasticity proteins nestin and c-fos expression in PC12 cells","volume":"55","author":"Gal","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7423","DOI":"10.1128\/MCB.25.17.7423-7431.2005","article-title":"p53-Dependent transcriptional repression of c-myc is required for G1 cell cycle arrest","volume":"25","author":"Ho","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4289","DOI":"10.1158\/0008-5472.CAN-11-3549","article-title":"Proteomic identification of a direct role for cyclin d1 in DNA damage repair","volume":"72","author":"Jirawatnotai","year":"2012","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Feng, X., Zhang, L., Shi, P., and Hu, Y. (2025). Advances in the study of FOXQ1: Biological functions and mechanisms. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1650022"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"722","DOI":"10.29271\/jcpsp.2025.06.722","article-title":"FOXQ1 suppressing apoptosis in colorectal cancer cells by p53 deacetylation","volume":"35","author":"Yang","year":"2025","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5077","DOI":"10.18632\/aging.205600","article-title":"FOXQ1 inhibits the progression of osteoarthritis by regulating pyroptosis","volume":"16","author":"Luo","year":"2024","journal-title":"Aging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"146272","DOI":"10.1016\/j.ijbiomac.2025.146272","article-title":"Dual role of Heme oxygenase-1 in disease progression and treatment: A literature review","volume":"321","author":"Ma","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bcp.2016.12.009","article-title":"Heme oxygenase (HO)-1 induction prevents Endoplasmic Reticulum stress-mediated endothelial cell death and impaired angiogenic capacity","volume":"127","author":"Maamoun","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.theriogenology.2024.03.003","article-title":"Heme oxygenase 1 (HO1) regulates autophagy and apoptosis via the PI3K\/AKT\/mTOR signaling pathway of yak Sertoli cells","volume":"220","author":"Yan","year":"2024","journal-title":"Theriogenology"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Huang, J., and Tan, R. (2024). HMOX1: A pivotal regulator of prognosis and immune dynamics in ovarian cancer. BMC Womens Health, 24.","DOI":"10.1186\/s12905-024-03309-3"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0021-5198(19)36228-6","article-title":"Anti-inflammatory activity of taxifolin","volume":"21","author":"Gupta","year":"1971","journal-title":"Jpn. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yang, C.J., Wang, Z.B., Mi, Y.Y., Gao, M.J., Lv, J.N., Meng, Y.H., Yang, B.Y., and Kuang, H.X. (2016). UHPLC-MS\/MS determination, pharmacokinetic, and bioavailability study of taxifolin in rat plasma after oral administration of its nanodispersion. Molecules, 21.","DOI":"10.3390\/molecules21040494"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.phymed.2008.10.002","article-title":"Determination and pharmacokinetic study of taxifolin in rabbit plasma by high-performance liquid chromatography","volume":"16","author":"Pozharitskaya","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.2174\/1567201815666180116090258","article-title":"Taxifolin: Evaluation through ex vivo permeations on human skin and porcine vaginal mucosa","volume":"15","author":"Alves","year":"2018","journal-title":"Curr. Drug Deliv."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:35:30Z","timestamp":1772642130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/3\/387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["biom16030387"],"URL":"https:\/\/doi.org\/10.3390\/biom16030387","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]}}}