{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:21:29Z","timestamp":1790968889787,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Long term exposure to solar ultraviolet B (UVB) radiation is one of the primary factors of premature skin aging and is referred to as photoaging. Also, mammalian skin exposed to UVB triggers an increase in production of \u03b1\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010MSH), which is critically involved in the pathogenesis of hyperpigmentary skin diseases. This study investigated the protective effect of limonene on UVB\u2010induced photodamage and photoaging in immortalized human skin keratinocytes (HaCaT) in vitro. Initially, we determined cell viability and levels of reactive oxygen species (ROS) in UVB\u2010irradiated HaCaT cells. Pretreatment with limonene increased cell viability followed by inhibition of intracellular ROS generation in UVB\u2010irradiated HaCaT cells. Interestingly, the antioxidative activity of limonene was directly correlated with an increase in expression of endogenous antioxidants, including heme oxygenase 1 (HO\u20101), NAD(P)H:quinone oxidoreductase 1 (NQO\u20101), and \u03b3\u2010glutamylcysteine synthetase (\u03b3\u2010GCLC), which was associated with enhanced nuclear translocation and activation of NF\u2010E2\u2010related factor\u20102 (Nrf2). Indeed, Nrf2 knockdown reduced limonene's protective effects. Additionally, we observed that limonene treatment inhibited UVB\u2010induced \u03b1\u2010MSH secretion followed by inhibition of proopiomelanocortin (POMC) via suppression of p53 transcriptional activation. Moreover, limonene prevented UVB\u2010mediated depletion of tight junction regulatory proteins, including occludin and zonula occludens\u20101. On the other hand, limonene treatment significantly decreased matrix metalloproteinase\u20102 levels in UVB\u2010irradiated HaCaT cells. Based on these results, limonene may have a dermato\u2010protective effect in skin cells by activating the Nrf2\u2010dependent cellular antioxidant defense system.<\/jats:p>","DOI":"10.1002\/tox.23646","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T08:57:03Z","timestamp":1662368223000},"page":"2897-2909","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Limonene protects human skin keratinocytes against\n                    <scp>UVB<\/scp>\n                    \u2010induced photodamage and photoaging by activating the Nrf2\u2010dependent antioxidant defense system"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8310-0546","authenticated-orcid":false,"given":"K. J. Senthil","family":"Kumar","sequence":"first","affiliation":[{"name":"Bachelor Program of Biotechnology National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gokila","family":"Vani","sequence":"additional","affiliation":[{"name":"Department of Forestry National Chung Hsing University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8579-3569","authenticated-orcid":false,"given":"Sheng\u2010Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Forestry National Chung Hsing University  Taichung Taiwan"},{"name":"Agricultural Biotechnology Research Center Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2007.12.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/skinbio.2013.176"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2009.00615.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jidsymp.2009.12"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms14059126"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/930164"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1189"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5507\/bp.2003.019"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01610-07"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.045"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.4953"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091973"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.385"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-8-13"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803833335"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13566"},{"issue":"12","key":"e_1_2_8_18_1","first-page":"1672","article-title":"Essential 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