{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:59:42Z","timestamp":1790006382277,"version":"4.0.1"},"reference-count":65,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T00:00:00Z","timestamp":1584662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["AGL2015-67995-C3-1-R, AGL2015-67995-C3-2-R AGL2015-67995-C3-3-R, RTI2018-096724-B-C21 and 2018-096724-B-C22"],"award-info":[{"award-number":["AGL2015-67995-C3-1-R, AGL2015-67995-C3-2-R AGL2015-67995-C3-3-R, RTI2018-096724-B-C21 and 2018-096724-B-C22"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conselleria d'Educaci\u00f3, Investigaci\u00f3, Cultura i Esport","doi-asserted-by":"publisher","award":["APOSTD\/2018\/097"],"award-info":[{"award-number":["APOSTD\/2018\/097"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012514","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red-Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n","doi-asserted-by":"publisher","award":["CIBERonb"],"award-info":[{"award-number":["CIBERonb"]}],"id":[{"id":"10.13039\/501100012514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Overexposure to solar ultraviolet (UV) radiation is the major cause of a variety of cutaneous disorders, including sunburn, photoaging, and skin cancers. UVB radiation (290\u2013320 nm) causes multiple forms of DNA damage, p53 induction, protein and lipid oxidation, and the generation of harmful reactive oxygen species (ROS). In recent years, botanicals containing polyphenols with antioxidant and anti-inflammatory properties as skin photoprotective agents have emerged. This study evaluated the protective effects of two formulations against UVB-induced damage in a skin cell model. One of the formulations (F2) contained a combination of citrus and olive extracts and the other one (F1) also contained a rosemary extract. The antioxidant capacity of both formulations was estimated by different in vitro methods, and the cell viability, intracellular ROS generation, mitochondrial depolarization, and DNA damage were studied in UVB-irradiated human keratinocytes. Both formulations exerted photoprotective effects on skin cells and decreased mitochondrial depolarization and DNA damage. F1 which contained iridoids, rosemary diterpenes, glycosides and aglycones of citrus flavanones, and monohydroxylated flavones exhibited higher cellular photoprotective effects and mitochondrial membrane potential restoration, as well as an enhanced capacity to decrease DNA double strand breaks and the DNA damage response. In contrast, F2, which contained mostly iridoids, citrus flavanone aglycones, and mono- and dihydroxylated flavones, exhibited a higher capacity to decrease intracellular ROS generation and radical scavenging capacity related to metal ion chelation. Both formulations showed a similar capability to decrease the number of apoptotic cells upon UVB radiation. Based on our results and those of others, we postulate that the stronger capacity of F1 to protect against UVB-induced DNA damage in human keratinocytes is related to the presence of rosemary diterpenes and citrus flavanone aglycones. Nevertheless, the presence of the dihydroxylated flavones in F2 may contribute to inhibiting the generation of metal-related free radicals. To confirm the efficacy of these formulations as potential candidates for oral\/topical photoprotection, human trials are required to circumvent the limitations of the cellular model.<\/jats:p>","DOI":"10.3390\/antiox9030255","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T11:42:11Z","timestamp":1584704531000},"page":"255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model"],"prefix":"10.3390","volume":"9","author":[{"given":"Noelia","family":"S\u00e1nchez-Marzo","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Instituto de Biolog\u00eda Molecular y Celular (IBMC), Miguel Hern\u00e1ndez University (UMH), 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-9671","authenticated-orcid":false,"given":"Almudena","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Instituto de Biolog\u00eda Molecular y Celular (IBMC), Miguel Hern\u00e1ndez University (UMH), 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-0795","authenticated-orcid":false,"given":"Enrique","family":"Barraj\u00f3n-Catal\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Instituto de Biolog\u00eda Molecular y Celular (IBMC), Miguel Hern\u00e1ndez University (UMH), 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n","family":"Castillo","sequence":"additional","affiliation":[{"name":"Nutrafur S.A., Camino Viejo de Pliego, km.2, 30820 Alcantarilla, Murcia, Spain"},{"name":"Department of Food Technology and Nutrition, Universidad Cat\u00f3lica San Antonio, 30107 Guadalupe de Maciascoque, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-7978","authenticated-orcid":false,"given":"Mar\u00eda","family":"Herranz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Instituto de Biolog\u00eda Molecular y Celular (IBMC), Miguel Hern\u00e1ndez University (UMH), 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-0696","authenticated-orcid":false,"given":"Vicente","family":"Micol","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n en Biotecnolog\u00eda Sanitaria de Elche (IDiBE), Instituto de Biolog\u00eda Molecular y Celular (IBMC), Miguel Hern\u00e1ndez University (UMH), 03202 Elche, Spain"},{"name":"CIBER, Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n, CIBERobn, Instituto de Salud Carlos III (ISCIII) (CB12\/03\/30038), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S247","DOI":"10.1016\/S0151-9638(09)72527-X","article-title":"Anatomy and physiology of skin and cutaneous annexes","volume":"136","author":"Dreno","year":"2009","journal-title":"Ann. Dermatol. Venereol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1600-0625.2006.00466.x","article-title":"Botanical antioxidants in the prevention of photocarcinogenesis and photoaging","volume":"15","author":"Afaq","year":"2006","journal-title":"Exp. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1365-4632.2004.02222.x","article-title":"Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis","volume":"43","author":"Sander","year":"2004","journal-title":"Int. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1046\/j.1468-3083.2003.00751.x","article-title":"Antioxidant activity, lipid peroxidation and skin diseases. What\u2019s new","volume":"17","author":"Briganti","year":"2003","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0300-483X(03)00150-1","article-title":"UV-induced skin damage","volume":"189","author":"Ichihashi","year":"2003","journal-title":"Toxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/PAT.0b013e32835f515c","article-title":"Non-melanoma skin cancer: Carcinogenesis and chemoprevention","volume":"45","author":"Chen","year":"2013","journal-title":"Pathology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000077461","article-title":"Mechanisms of DNA double strand break repair and chromosome aberration formation","volume":"104","author":"Iliakis","year":"2004","journal-title":"Cytogenet. Genome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1034\/j.1600-0781.2000.160501.x","article-title":"Molecular mechanisms of UV-induced apoptosis","volume":"16","author":"Kulms","year":"2000","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.1751-1097.2007.00226.x","article-title":"The protective role of melanin against UV damage in human skin","volume":"84","author":"Brenner","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s00403-009-0994-y","article-title":"The UV response of the skin: A review of the MAPK, NFkappaB and TNFalpha signal transduction pathways","volume":"302","author":"Muthusamy","year":"2010","journal-title":"Arch. Dermatol. Res."},{"key":"ref_11","first-page":"97939","article-title":"EGFR activation and ultraviolet light-induced skin carcinogenesis","volume":"2007","author":"Hansen","year":"2007","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1749-6632.2002.tb04602.x","article-title":"Ultraviolet-B irradiation and matrix metalloproteinases: From induction via signaling to initial events","volume":"973","author":"Brenneisen","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0041-008X(02)00014-5","article-title":"Prevention of short-term ultraviolet B radiation-mediated damages by resveratrol in SKH-1 hairless mice","volume":"186","author":"Afaq","year":"2003","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","first-page":"3864","article-title":"Green tea polyphenol treatment to human skin prevents formation of ultraviolet light B-induced pyrimidine dimers in DNA","volume":"6","author":"Katiyar","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_15","first-page":"233","article-title":"Apigenin and cancer chemoprevention: Progress, potential and promise (review)","volume":"30","author":"Patel","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1093\/carcin\/17.1.73","article-title":"Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein","volume":"17","author":"Wei","year":"1996","journal-title":"Carcinogenesis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1021\/jf900344d","article-title":"Inhibition of UVA and UVB radiation-induced lipid oxidation by quercetin","volume":"57","author":"Fahlman","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.5487\/TR.2017.33.2.097","article-title":"Terpenes from Forests and Human Health","volume":"33","author":"Cho","year":"2017","journal-title":"Toxicol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1111\/php.12711","article-title":"Phytochemicals for the Prevention of Photocarcinogenesis","volume":"93","author":"Pearlman","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1039\/c5pp00409h","article-title":"Mechanism of Aloe Vera extract protection against UVA: Shelter of lysosomal membrane avoids photodamage","volume":"15","author":"Rodrigues","year":"2016","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/j.1751-1097.2007.00157.x","article-title":"Inhibition of UVB-mediated oxidative stress and markers of photoaging in immortalized HaCaT keratinocytes by pomegranate polyphenol extract POMx","volume":"83","author":"Zaid","year":"2007","journal-title":"Photochem. Photobiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Feher, P., Ujhelyi, Z., Varadi, J., Fenyvesi, F., Roka, E., Juhasz, B., Varga, B., Bombicz, M., Priksz, D., and Bacskay, I. (2016). Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes. Molecules, 21.","DOI":"10.3390\/molecules21101269"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-S\u00e1nchez, A., Barraj\u00f3n-Catal\u00e1n, E., Herranz-L\u00f3pez, M., and Micol, V. (2018). Nutraceuticals for skin care: A comprehensive review of human clinical studies. Nutrients, 10.","DOI":"10.3390\/nu10040403"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jdermsci.2016.08.004","article-title":"Lemon balm extract (Melissa officinalis, L.) promotes melanogenesis and prevents UVB-induced oxidative stress and DNA damage in a skin cell model","volume":"84","author":"Castillo","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jphotobiol.2014.04.007","article-title":"Protective effects of citrus and rosemary extracts on UV-induced damage in skin cell model and human volunteers","volume":"136","author":"Caturla","year":"2014","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.5344\/ajev.1965.16.3.144","article-title":"Colorimetry of Total Phenolics with Phosphomolybdic-Phosphotungstic Acid Reagents","volume":"16","author":"Singleton","year":"1965","journal-title":"Am. J. Enol. Vitic."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nprot.2007.102","article-title":"Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent","volume":"2","author":"Ainsworth","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1021\/jf030723c","article-title":"The chemistry behind antioxidant capacity assays","volume":"53","author":"Huang","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.1021\/jf010586o","article-title":"Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe","volume":"49","author":"Ou","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The ferric reducing ability of plasma (FRAP) as a measure of \u201cantioxidant power\u201d: The FRAP assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.dnarep.2014.03.002","article-title":"Cytolethal distending toxin (CDT) is a radiomimetic agent and induces persistent levels of DNA double-strand breaks in human fibroblasts","volume":"18","author":"Fahrer","year":"2014","journal-title":"DNA Repair"},{"key":"ref_32","first-page":"286","article-title":"Interexperimental and interindividual variations of DNA repair capacities after UV-B and UV-C irradiations of human keratinocytes and fibroblasts","volume":"79","author":"Chazal","year":"2004","journal-title":"Photochem. Photobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1517\/13543776.2014.1000863","article-title":"Natural compounds for solar photoprotection: A patent review","volume":"25","author":"Serafini","year":"2015","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/med.21301","article-title":"Flavonoid-metal ion complexes: A novel class of therapeutic agents","volume":"34","author":"Selvaraj","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Martinez, R.M., Pinho-Ribeiro, F.A., Steffen, V.S., Silva, T.C., Caviglione, C.V., Bottura, C., Fonseca, M.J., Vicentini, F.T., Vignoli, J.A., and Baracat, M.M. (2016). Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146296"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/1750-3841.13613","article-title":"Antioxidant Effect of Natural Table Olives Phenolic Extract Against Oxidative Stress and Membrane Damage in Enterocyte-Like Cells","volume":"82","author":"Serreli","year":"2017","journal-title":"J. Food Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.fct.2008.11.026","article-title":"Rosmarinic acid, a photo-protective agent against UV and other ionizing radiations","volume":"47","author":"Gabaldon","year":"2009","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1021\/jf950374p","article-title":"Antioxidant Activity of a Rosemary Extract and Its Constituents, Carnosic Acid, Carnosol, and Rosmarinic Acid, in Bulk Oil and Oil-in-Water Emulsion","volume":"44","author":"Frankel","year":"1996","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10068-013-0226-2","article-title":"Carnosic acid protects biomolecules from free radical-mediated oxidative damage in vitro","volume":"22","author":"Xiang","year":"2013","journal-title":"Food Sci. Biotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/exd.12138","article-title":"Carnosic acid, a phenolic diterpene from rosemary, prevents UV-induced expression of matrix metalloproteinases in human skin fibroblasts and keratinocytes","volume":"22","author":"Park","year":"2013","journal-title":"Exp. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jnutbio.2005.05.009","article-title":"The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells","volume":"17","author":"Gao","year":"2006","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.chemphyslip.2009.11.004","article-title":"Effects of verbascoside, a phenylpropanoid glycoside from lemon verbena, on phospholipid model membranes","volume":"163","author":"Funes","year":"2010","journal-title":"Chem. Phys. Lipids"},{"key":"ref_43","first-page":"25","article-title":"Correlation between the cellular metabolism of quercetin and its glucuronide metabolite and oxidative stress in hypertrophied 3T3-L1 adipocytes","volume":"25","author":"Galvez","year":"2017","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/cr.2010.178","article-title":"Crosstalk of reactive oxygen species and NF-kappaB signaling","volume":"21","author":"Morgan","year":"2011","journal-title":"Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.phymed.2015.03.015","article-title":"Lemon verbena (Lippia citriodora) polyphenols alleviate obesity-related disturbances in hypertrophic adipocytes through AMPK-dependent mechanisms","volume":"22","author":"Menendez","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1021\/acs.jnatprod.5b00198","article-title":"Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice","volume":"78","author":"Martinez","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3797\/scipharm.0912-18","article-title":"Oleuropein in olive and its pharmacological effects","volume":"78","author":"Omar","year":"2010","journal-title":"Sci. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2011.02.005","article-title":"Carnosol: A promising anti-cancer and anti-inflammatory agent","volume":"305","author":"Johnson","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1289\/ehp.02110301","article-title":"Mitochondrial membrane potential: A novel biomarker of oxidative environmental stress","volume":"110","author":"Kreps","year":"2002","journal-title":"Environ. Health Perspect."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.phrs.2015.12.027","article-title":"Epigallocatechin gallate and mitochondria-A story of life and death","volume":"104","author":"Oliveira","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.abb.2008.04.003","article-title":"(-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells","volume":"476","author":"Na","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3892\/ijmm.2017.3134","article-title":"Naringenin reduces oxidative stress and improves mitochondrial dysfunction via activation of the Nrf2\/ARE signaling pathway in neurons","volume":"40","author":"Wang","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.0022-202X.2005.23670.x","article-title":"Ultraviolet A irradiation induces NF-E2-related factor 2 activation in dermal fibroblasts: Protective role in UVA-induced apoptosis","volume":"124","author":"Hirota","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tiv.2015.12.005","article-title":"Protective effect of carnosic acid against paraquat-induced redox impairment and mitochondrial dysfunction in SH-SY5Y cells: Role for PI3K\/Akt\/Nrf2 pathway","volume":"32","author":"Ferreira","year":"2016","journal-title":"Toxicol. In Vitro"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1093\/carcin\/bgl152","article-title":"Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes","volume":"28","author":"Bivik","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1038\/jid.2010.124","article-title":"The flavonoid luteolin increases the resistance of normal, but not malignant keratinocytes, against UVB-induced apoptosis","volume":"130","author":"Verschooten","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1751-1097.2007.00255.x","article-title":"Naringenin protects HaCaT human keratinocytes against UVB-induced apoptosis and enhances the removal of cyclobutane pyrimidine dimers from the genome","volume":"84","author":"Zhu","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.dnarep.2004.03.024","article-title":"H2AX: The histone guardian of the genome","volume":"3","author":"Lee","year":"2004","journal-title":"DNA Repair"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/php.12368","article-title":"Oxidatively generated damage to cellular DNA by UVB and UVA radiation","volume":"91","author":"Cadet","year":"2015","journal-title":"Photochem. Photobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"42462","DOI":"10.1074\/jbc.C100466200","article-title":"ATM phosphorylates histone H2AX in response to DNA double-strand breaks","volume":"276","author":"Burma","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11113","DOI":"10.1073\/pnas.95.19.11113","article-title":"Indirect mutagenesis by oxidative DNA damage: Formation of the pyrimidopurinone adduct of deoxyguanosine by base propenal","volume":"95","author":"Dedon","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1021\/jf0581574","article-title":"Radioprotective-antimutagenic effects of rosemary phenolics against chromosomal damage induced in human lymphocytes by gamma-rays","volume":"54","author":"Castillo","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1259\/bjr\/30930369","article-title":"Liposoluble antioxidants provide an effective radioprotective barrier","volume":"82","author":"Alcaraz","year":"2009","journal-title":"Br. J. Radiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"a012559","DOI":"10.1101\/cshperspect.a012559","article-title":"DNA base damage by reactive oxygen species, oxidizing agents, and UV radiation","volume":"5","author":"Cadet","year":"2013","journal-title":"Cold Spring Harb. Perspect. 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