{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:02:12Z","timestamp":1789038132892,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,25]],"date-time":"2018-12-25T00:00:00Z","timestamp":1545696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Applied Basic Research Programs of Qinghai Province","award":["2015-ZJ-733"],"award-info":[{"award-number":["2015-ZJ-733"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81303185"],"award-info":[{"award-number":["81303185"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a racemic mixture and has an anxiolytic effect in rodents. Previously, we have shown that fluoxetine can up-regulate melanin synthesis in B16F10 melanoma cells and normal human melanocytes (NMHM). However, the role of r-fluoxetine and s-fluoxetine, in the regulation of melanin synthesis, is still unknown. Here, we show how r-fluoxetine plays a critical role in fluoxetine enhancing melanogenesis, both in vivo and vitro, by up-regulating tyrosinase (TYR) and the microphthalmia-associated transcription factor (MITF) expression, whereas, s-fluoxetine does not show any effect in the vivo and vitro systems. In addition, we found that r-fluoxetine induced melanin synthesis through the serotonin1A receptor (5-HT1A) and serotonin 2A receptor (5-HT2A). Furthermore, r-fluoxetine increased the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), without affecting the phosphorylation of extracellularly responsive kinase (ERK1\/2) and c-Jun N-terminal kinase (JNK). These data suggest that r-fluoxetine may be used as a drug for skin hypopigmentation disorders.<\/jats:p>","DOI":"10.3390\/ijms20010080","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T11:31:21Z","timestamp":1545823881000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["R-Fluoxetine Increases Melanin Synthesis Through a 5-HT1A\/2A Receptor and p38 MAPK Signaling Pathways"],"prefix":"10.3390","volume":"20","author":[{"given":"Li","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengsi","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siran","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1600-0625.2007.00675.x","article-title":"Regulation of melanogenesis--controversies and new concepts","volume":"17","author":"Schallreuter","year":"2008","journal-title":"Exp. 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