{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:32:58Z","timestamp":1790155978751,"version":"4.0.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["GINOP- 2.3.2-15-2016-00005"],"award-info":[{"award-number":["GINOP- 2.3.2-15-2016-00005"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian National Research Development and Innovation Fund","award":["OTKA K120206"],"award-info":[{"award-number":["OTKA K120206"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.<\/jats:p>","DOI":"10.3390\/molecules24091652","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T10:03:17Z","timestamp":1556272997000},"page":"1652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Silymarin: Friend or Foe of UV Exposed Keratinocytes?"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-6862","authenticated-orcid":false,"given":"Eszter","family":"Fidrus","sequence":"first","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Ujhelyi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1lma","family":"Feh\u00e9r","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Heged\u0171s","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter Anna","family":"Janka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Paragh","sequence":"additional","affiliation":[{"name":"Departments of Dermatology and Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bos","family":"Vasas","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildik\u00f3","family":"B\u00e1cskay","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Debrecen, Nagyerdei k\u00f6r\u00fat 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9va","family":"Remenyik","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.freeradbiomed.2016.10.488","article-title":"Oxidatively-Generated damage to DNA and proteins mediated by photosensitized UVA","volume":"107","author":"Brem","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0076-6879(00)19035-4","article-title":"Photocarcinogenesis: UVA vs. UVB","volume":"319","year":"2000","journal-title":"Methods Enzymol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/09553000902740150","article-title":"Cellular and sub-cellular responses to UVA in relation to carcinogenesis","volume":"85","author":"Ridley","year":"2009","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1039\/b504573h","article-title":"Endogenous UVA-photosensitizers: Mediators of skin photodamage and novel targets for skin photoprotection","volume":"5","author":"Wondrak","year":"2006","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jphotobiol.2005.03.011","article-title":"Changes in ultraviolet absorbance and hence in protective efficacy against lipid peroxidation of organic sunscreens after UVA irradiation","volume":"82","author":"Damiani","year":"2006","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1046\/j.1523-1747.2002.01708.x","article-title":"Photoaging is associated with protein oxidation in human skin in vivo","volume":"118","author":"Sander","year":"2002","journal-title":"J. Investig. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"13538","DOI":"10.1073\/pnas.0504497102","article-title":"UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae","volume":"102","author":"Kozmin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1111\/j.1349-7006.2011.02005.x","article-title":"Downregulation of Cockayne syndrome B protein reduces human 8-oxoguanine DNA glycosylase-1 expression and repair of UV radiation-induced 8-oxo-7,8-dihydro-2\u2019-deoxyguanine","volume":"102","author":"Javeri","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10058","DOI":"10.1073\/pnas.0502311102","article-title":"DNA lesions induced by UV A1 and B radiation in human cells: Comparative analyses in the overall genome and in the p53 tumor suppressor gene","volume":"102","author":"Besaratinia","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1039\/c1pp05219e","article-title":"Unravelling UVA-induced mutagenesis","volume":"11","author":"Sage","year":"2012","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9221","DOI":"10.1021\/bi034593c","article-title":"Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation","volume":"42","author":"Douki","year":"2003","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mrfmmm.2004.07.011","article-title":"Larger yield of cyclobutane dimers than 8-oxo-7,8-dihydroguanine in the DNA of UVA-irradiated human skin cells","volume":"556","author":"Courdavault","year":"2004","journal-title":"Mutat. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.dnarep.2005.05.001","article-title":"Repair of the three main types of bipyrimidine DNA photoproducts in human keratinocytes exposed to UVB and UVA radiations","volume":"4","author":"Courdavault","year":"2005","journal-title":"DNA Repair"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lo, H.L., Nakajima, S., Ma, L., Walter, B., Yasui, A., Ethell, D.W., and Owen, L.B. (2005). Differential biologic effects of CPD and 6-4PP UV-induced DNA damage on the induction of apoptosis and cell-cycle arrest. BMC Cancer, 5.","DOI":"10.1186\/1471-2407-5-135"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/sj.cdd.4401224","article-title":"Apoptosis and efficient repair of DNA damage protect human keratinocytes against UVB","volume":"10","author":"Teson","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1751-1097.1997.tb03213.x","article-title":"UVB-induced cyclobutane pyrimidine dimer frequency correlates with skin cancer mutational hotspots in p53","volume":"66","author":"Drouin","year":"1997","journal-title":"Photochem. Photobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"44688","DOI":"10.1074\/jbc.M107696200","article-title":"Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations induced by UVB irradiation in mammalian cells","volume":"276","author":"You","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Szabados-Furjesi, P., Pajtas, D., Barta, A., Csepanyi, E., Kiss-Szikszai, A., Tosaki, A., and Bak, I. (2018). Synthesis, in Vitro Biological Evaluation, and Oxidative Transformation of New Flavonol Derivatives: The Possible Role of the Phenyl-N,N-Dimethylamino Group. Molecules, 23.","DOI":"10.3390\/molecules23123161"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3892\/mmr.2016.5517","article-title":"Luteolin decreases the UVA-induced autophagy of human skin fibroblasts by scavenging ROS","volume":"14","author":"Yan","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1111\/php.12619","article-title":"Photoprotective Potential of Baccharis antioquensis (Asteraceae) as Natural Sunscreen","volume":"92","author":"Winkler","year":"2016","journal-title":"Photochem. Photobiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1007\/BF02977608","article-title":"Structure activity relationship of antioxidative property of flavonoids and inhibitory effect on matrix metalloproteinase activity in UVA-irradiated human dermal fibroblast","volume":"30","author":"Sim","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/ijc.10730","article-title":"The green tea polyphenol, epigallocatechin-3-gallate, protects against the oxidative cellular and genotoxic damage of UVA radiation","volume":"102","author":"Tobi","year":"2002","journal-title":"Int. J. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0891-5849(98)00212-3","article-title":"Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line","volume":"26","author":"Saliou","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1177\/1534735407301441","article-title":"Chemopreventive efficacy of silymarin in skin and prostate cancer","volume":"6","author":"Deep","year":"2007","journal-title":"Integr. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0944-7113(00)80017-3","article-title":"Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase","volume":"7","author":"Gupta","year":"2000","journal-title":"Phytomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bcp.2013.01.026","article-title":"Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells","volume":"85","author":"Vaid","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jdermsci.2007.06.008","article-title":"Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes","volume":"48","year":"2007","journal-title":"J. Dermatol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/jnci\/89.8.556","article-title":"Protective effects of silymarin against photocarcinogenesis in a mouse skin model","volume":"89","author":"Katiyar","year":"1997","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Vost\u00e1lov\u00e1, J., Tinkov\u00e1, E., Biedermann, D., Kosina, P., Ulrichov\u00e1, J., and Rajnochov\u00e1 Svobodov\u00e1, A. (2019). Skin Protective Activity of Silymarin and its Flavonolignans. Molecules, 24.","DOI":"10.3390\/molecules24061022"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jphotobiol.2017.03.015","article-title":"Hydrogel containing silibinin-loaded pomegranate oil based nanocapsules exhibits anti-inflammatory effects on skin damage UVB radiation-induced in mice","volume":"170","author":"Marchiori","year":"2017","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/carcin\/bgw106","article-title":"Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis","volume":"38","author":"Rigby","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/j.1751-1097.2011.01050.x","article-title":"Silibinin is a potent sensitizer of UVA radiation-induced oxidative stress and apoptosis in human keratinocyte HaCaT cells","volume":"88","author":"Narayanapillai","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jphotobiol.2016.01.011","article-title":"Phototoxic potential of silymarin and its bioactive components","volume":"156","author":"Biedermann","year":"2016","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1158\/1535-7163.207.4.2","article-title":"Silymarin induces apoptosis primarily through a p53-dependent pathway involving Bcl-2\/Bax, cytochrome c release, and caspase activation","volume":"4","author":"Katiyar","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/php.12716","article-title":"Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways","volume":"93","author":"Baptista","year":"2017","journal-title":"Photochem. Photobiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Feh\u00e9r, P., Ujhelyi, Z., V\u00e1radi, J., Fenyvesi, F., R\u00f3ka, E., Juh\u00e1sz, B., Varga, B., Bombicz, M., Priksz, D., and B\u00e1cskay, 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_37","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1111\/php.12048","article-title":"Hydrochlorothiazide enhances UVA-induced DNA damage","volume":"89","author":"Kunisada","year":"2013","journal-title":"Photochem. Photobiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.tiv.2010.03.007","article-title":"Cyclobutane pyrimidine dimers are photosensitised by carprofen plus UVA in human HaCaT cells","volume":"24","author":"Robinson","year":"2010","journal-title":"Toxicol. In Vitro"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0021-9673(02)01971-4","article-title":"Analysis of the active components of silymarin","volume":"990","author":"Kvasnicka","year":"2003","journal-title":"J. Chromatogr. A"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1093\/carcin\/bgg188","article-title":"Dual efficacy of silibinin in protecting or enhancing ultraviolet B radiation-caused apoptosis in HaCaT human immortalized keratinocytes","volume":"25","author":"Dhanalakshmi","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.pdpdt.2018.04.018","article-title":"Photodynamic therapy does not induce cyclobutane pyrimidine dimers in the presence of melanin","volume":"22","author":"Mudambi","year":"2018","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1083\/jcb.106.3.761","article-title":"Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line","volume":"106","author":"Boukamp","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_43","unstructured":"Kahol, A.P., Singh, K.L., Tandon, S., and Kumar, S. (2001). Process for Isolation of Hepatoprotective Agent Silymarin from the Seeds of the Plant Silybum marianum. (US6309678B1), U.S. Patent."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10337-011-2163-7","article-title":"Identification of Silymarin Constituents: An Improved HPLC-MS Method","volume":"75","author":"Kuki","year":"2012","journal-title":"Chromatographia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jphotobiol.2013.09.010","article-title":"Transfection of pseudouridine-modified mRNA encoding CPD-photolyase leads to repair of DNA damage in human keratinocytes: A new approach with future therapeutic potential","volume":"129","author":"Boros","year":"2013","journal-title":"J. Photochem. Photobiol. B"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1652\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:47:27Z","timestamp":1760186847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/9\/1652"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,26]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["molecules24091652"],"URL":"https:\/\/doi.org\/10.3390\/molecules24091652","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,26]]}}}