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Many such anti\u2010melanogenic agents are associated with side effects, such as contact dermatitis and high toxicity, and also exhibit poor skin penetration. Considerable recent research has focused on plant\u2010derived products as alternatives to chemotherapeutic agents that possess fewer side effects. In the current study, we investigated the anti\u2010melanogenic effects of extracellular vesicles (EVs) extracted from leaves and stems of\n                    <jats:italic>Dendropanax morbifera<\/jats:italic>\n                    . Using spectrophotometric and biochemical approaches, we found that leaf\u2010derived extracellular vesicles (LEVs) and stem\u2010derived extracellular vesicles (SEVs) reduced melanin content and tyrosinase (TYR) activity in the B16BL6\u00a0mouse melanoma cell line in a concentration\u2010dependent manner. An electron microscopy analysis further confirmed that LEVs and SEVs induce a concentration\u2010dependent decrease in melanin content in melanoma cells. Both LEVs and SEVs exerted a greater whitening effect on melanoma cells than arbutin, used as a positive control, with LEVs producing the greater effect. Notably, neither LEVs nor SEVs induced significant cytotoxicity. We also examined the effects of plant\u2010derived EVs on the expression of tyrosinase\u2010related proteins (TRPs) in melanoma cells. LEVs inhibited expression of melanogenesis\u2010related genes and proteins, including microphthalmia\u2010associated transcription factor (MITF), TYR, TRP\u20101 and TRP\u20102. In a human epidermis model, LEVs exerted a stronger inhibitory effect on melanin production than arbutin. Collectively, our data suggest that LEVs from\n                    <jats:italic>D. morbifera<\/jats:italic>\n                    may be a novel candidate natural substance for use as an anti\u2010melanogenic agent in cosmeceutical formulations.\n                  <\/jats:p>","DOI":"10.1080\/20013078.2019.1703480","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T06:21:05Z","timestamp":1576650065000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":186,"title":["Anti\u2010melanogenic effects of extracellular vesicles derived from plant leaves and stems in mouse melanoma cells and human healthy skin"],"prefix":"10.1002","volume":"9","author":[{"given":"Ruri","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Integrative Biosciences University of Brain Education Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Ju","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Integrative Biosciences University of Brain Education Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biosciences University of Brain Education Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yehjoo","family":"Sohn","sequence":"additional","affiliation":[{"name":"Department of Integrative Biosciences University of Brain Education Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Yun","family":"Min","sequence":"additional","affiliation":[{"name":"Biomedical Omics Group Korea Basic Science Institute Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Omics Group Korea Basic Science Institute Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dokyun","family":"Na","sequence":"additional","affiliation":[{"name":"School of Integrative Engineering Chung\u2010Ang University Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju Hun","family":"Yeon","sequence":"additional","affiliation":[{"name":"Department of Integrative Biosciences University of Brain Education Cheonan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,18]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2006.00345.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1995.01690240119022"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.136.7.841"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4725.2004.30058.x"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1701"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.09.016"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2009.06.003"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1473-2165.2005.40202.x"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2007.04.012"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsi.2014.07.003"},{"issue":"4","key":"e_1_2_10_12_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/molecules22040514","article-title":"Anti\u2010melanogenic properties of Greek plants. 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