{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:20:52Z","timestamp":1792120852871,"version":"4.4.0"},"reference-count":48,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T00:00:00Z","timestamp":1589587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skin is a major target of oxidative stress. Increasing evidence suggests that oxidative stress is the cause of melanocyte disappearance in vitiligo, which is an acquired pigmentary skin disorder characterized by patches of skin that have lost pigmentation. New herbal extracts with antioxidant activity are therefore being studied. 6-Shogaol (6-SG), an active compound from ginger, is capable of attenuating oxidative stress-induced ageing and neurotoxicity. Subsequently, to investigate whether 6-SG could protect melanocytes from oxidative stress, cultured human primary epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of 6-SG. The 6-SG exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, the 6-SG treatment activated the Nrf2-antioxidant response element signaling pathway by upregulating the mRNA expression of the antioxidant enzyme heme oxygenase 1 (HO-1), and protein expression of Nrf2, NAD(P)H: quinine oxidoreductase 1 (Nqo1), and HO-1. Furthermore, the 6-SG also displayed protective effects on melanocytes against Rhododendrol-induced oxidative stress. We concluded that 6-SG protects melanocytes against oxidative stress in vitro, and its protective effect is associated with the activation of the Nrf2-antioxidant response element signaling pathway. 6-SG, therefore, has potential for use in the prevention of melanocyte loss in the early stages of vitiligo or other pigmentary disorders.<\/jats:p>","DOI":"10.3390\/ijms21103537","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T02:43:42Z","timestamp":1589769822000},"page":"3537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["6-Shogaol Protects Human Melanocytes against Oxidative Stress through Activation of the Nrf2-Antioxidant Response Element Signaling Pathway"],"prefix":"10.3390","volume":"21","author":[{"given":"Lingli","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 545-0041, Japan"},{"name":"Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanting","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Pigmentation Research and Therapeutics, Graduate School of Medicine, Osaka City University, Osaka 545-0041, Japan"},{"name":"Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1038\/jid.2014.65","article-title":"Melanocytes as instigators and victims of oxidative stress","volume":"134","author":"Denat","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","first-page":"160","article-title":"Clinical practice. Vitiligo","volume":"360","author":"Taieb","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_3","first-page":"15011","article-title":"Vitiligo. Nature reviews","volume":"1","author":"Picardo","year":"2015","journal-title":"Dis. Prim."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1034\/j.1600-0749.13.s8.9.x","article-title":"Intrinsic and extrinsic pathomechanisms in vitiligo","volume":"13","author":"Taieb","year":"2000","journal-title":"Pigment. Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/1523-1747.ep12335801","article-title":"Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo","volume":"109","author":"Maresca","year":"1997","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/sj.jidsp.5640189","article-title":"In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase","volume":"4","author":"Schallreuter","year":"1999","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1600-0749.1998.tb00714.x","article-title":"Epidermal oxidative stress in vitiligo","volume":"11","author":"Passi","year":"1998","journal-title":"Pigment Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1468-3083.2004.01080.x","article-title":"The role of oxidants and antioxidants in generalized vitiligo at tissue level","volume":"18","author":"Yildirim","year":"2004","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1346-8138.2003.tb00356.x","article-title":"The role of oxidants and antioxidants in generalized vitiligo","volume":"30","author":"Yildirim","year":"2003","journal-title":"J. Dermatol."},{"key":"ref_10","first-page":"701","article-title":"Evaluation of total oxidant and antioxidant status in localized and generalized vitiligo","volume":"38","author":"Akoglu","year":"2013","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/ejlt.200600127","article-title":"Natural antioxidants from herbs and spices","volume":"108","author":"Yanishlieva","year":"2006","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1515\/DMDI.2001.18.3-4.159","article-title":"Ginger: An ethnomedical, chemical and pharmacological review","volume":"18","author":"Afzal","year":"2001","journal-title":"Drug Metab. Drug Interact."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1089\/rej.2012.1389","article-title":"Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats","volume":"16","author":"Zeng","year":"2013","journal-title":"Rejuvenation Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.neuropharm.2012.03.016","article-title":"6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection","volume":"63","author":"Ha","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.fct.2011.03.005","article-title":"[6]-Gingerol attenuates beta-amyloid-induced oxidative cell death via fortifying cellular antioxidant defense system","volume":"49","author":"Lee","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bellei, B., Pitisci, A., Ottaviani, M., Ludovici, M., Cota, C., Luzi, F., Dell\u2019Anna, M.L., and Picardo, M. (2013). Vitiligo: A possible model of degenerative diseases. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059782"},{"key":"ref_17","first-page":"202","article-title":"Clinical trial of certain ayurvedic medicines indicated in vitiligo","volume":"9","author":"Donata","year":"1990","journal-title":"Anc. Sci. Life"},{"key":"ref_18","first-page":"40","article-title":"Clinical Observation on The Curative Effect of Plum Blossom Needle, Ginger and Acupoint Injection of Autologous Venous Blood in The Treatment of Vitilligo","volume":"2012","author":"She","year":"2012","journal-title":"J. Pract. Tradit. Chin. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.fct.2006.11.002","article-title":"Cancer preventive properties of ginger: A brief review","volume":"45","author":"Shukla","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_20","first-page":"836","article-title":"Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol","volume":"7","author":"Suekawa","year":"1984","journal-title":"J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.bbrc.2005.07.076","article-title":"[6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivo","volume":"335","author":"Kim","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0049-3848(01)00338-3","article-title":"Gingerols and related analogues inhibit arachidonic acid-induced human platelet serotonin release and aggregation","volume":"103","author":"Koo","year":"2001","journal-title":"Thromb. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jep.2009.10.004","article-title":"Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol","volume":"127","author":"Dugasani","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1002\/mnfr.201000108","article-title":"Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells","volume":"54","author":"Weng","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.fitote.2011.12.028","article-title":"Cytotoxic, cytoprotective and antioxidant effects of isolated phenolic compounds from fresh ginger","volume":"83","author":"Peng","year":"2012","journal-title":"Fitoterapia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/med.2610080405","article-title":"Progress in the chemistry of melanins and related metabolites","volume":"8","author":"Prota","year":"1988","journal-title":"Med. Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1128\/MCB.15.3.1833","article-title":"Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene","volume":"15","author":"Yasumoto","year":"1995","journal-title":"Mol. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.molmed.2004.09.003","article-title":"Nrf2-Keap1 defines a physiologically important stress response mechanism","volume":"10","author":"Motohashi","year":"2004","journal-title":"Trends Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.freeradbiomed.2009.07.035","article-title":"Nrf2:INrf2 (Keap1) signaling in oxidative stress","volume":"47","author":"Kaspar","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.jdermsci.2015.02.001","article-title":"Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma","volume":"77","author":"Tokura","year":"2015","journal-title":"J. Dermatol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/pcmr.12275","article-title":"Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: Implications for melanocyte toxicity","volume":"27","author":"Ito","year":"2014","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3164\/jcbn.16-38","article-title":"Generation of hydroxyl radicals and singlet oxygen during oxidation of rhododendrol and rhododendrol-catechol","volume":"60","author":"Miyaji","year":"2017","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jdermsci.2018.06.007","article-title":"Substantial evidence for the rhododendrol-induced generation of hydroxyl radicals that causes melanocyte cytotoxicity and induces chemical leukoderma","volume":"91","author":"Gabe","year":"2018","journal-title":"J Dermatol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1038\/jid.2011.56","article-title":"Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway","volume":"131","author":"Jian","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1046\/j.0022-202X.2004.22230.x","article-title":"Perturbed 6-tetrahydrobiopterin recycling via decreased dihydropteridine reductase in vitiligo: More evidence for H2O2 stress","volume":"122","author":"Hasse","year":"2004","journal-title":"J. Investig. Dermatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/sj.jid.5700538","article-title":"Oxidative stress via hydrogen peroxide affects proopiomelanocortin peptides directly in the epidermis of patients with vitiligo","volume":"127","author":"Spencer","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1210\/en.2007-1317","article-title":"The Ca2+-binding capacity of epidermal furin is disrupted by H2O2-mediated oxidation in vitiligo","volume":"149","author":"Spencer","year":"2008","journal-title":"Endocrinology"},{"key":"ref_39","first-page":"2403","article-title":"Abnormal nuclear translocation of nuclear factor-E2 related factor 2 in the lesion of vitiligo","volume":"88","author":"Guan","year":"2008","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/j.1600-0625.2008.00752.x","article-title":"The susceptibility to vitiligo is associated with NF-E2-related factor2 (Nrf2) gene polymorphisms: A study on Chinese Han population","volume":"17","author":"Guan","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1038\/jid.2014.241","article-title":"Oxidative stress and vitiligo: The Nrf2-ARE signaling connection","volume":"134","author":"Qiu","year":"2014","journal-title":"J. Invest Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1038\/jid.2014.152","article-title":"Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: A possible mechanism for melanocyte degeneration in vitiligo","volume":"134","author":"Jian","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1177\/0260106013506668","article-title":"Attenuation of gentamycin-induced nephrotoxicity in rats by dietary inclusion of ginger (Zingiber officinale) and turmeric (Curcuma longa) rhizomes","volume":"21","author":"Ademiluyi","year":"2012","journal-title":"Nutr. Health"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jep.2004.11.011","article-title":"Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats","volume":"97","author":"Bhandari","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.fct.2006.11.014","article-title":"Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure","volume":"45","author":"Ajith","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3109\/10715762.2013.778403","article-title":"Time course of Keap1-Nrf2 pathway expression after experimental intracerebral haemorrhage: Correlation with brain oedema and neurological deficit","volume":"47","author":"Shang","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jid.2017.10.007","article-title":"Uncoupling of ER\/Mitochondrial Oxidative Stress in mTORC1 Hyperactivation-Associated Skin Hypopigmentation","volume":"138","author":"Yang","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1038\/jid.2014.120","article-title":"Histamine Contributes to Tissue Remodeling via Periostin Expression","volume":"134","author":"Yang","year":"2014","journal-title":"J. Investig. Dermatol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/10\/3537\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:29:37Z","timestamp":1760174977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/10\/3537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,16]]},"references-count":48,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21103537"],"URL":"https:\/\/doi.org\/10.3390\/ijms21103537","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,16]]}}}