title: [6]-Shogaol inhibits α-MSH-induced melanogenesis through the acceleration of ERK and PI3K/Akt-mediated MITF degradation.
abstract: [6]-Shogaol is the main biologically active component of ginger. Previous reports showed that [6]-shogaol has several pharmacological characteristics, such as antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties. However, the effects of [6]-shogaol on melanogenesis remain to be elucidated. The study aimed to evaluate the potential skin whitening mechanisms of [6]-shogaol. The effects of [6]-shogaol on cell viability, melanin content, tyrosinase activity, and the expression of the tyrosinase and microphthalmia-associated transcription factor (MITF) were measured. The results revealed that [6]-shogaol effectively suppresses tyrosinase activity and the amount of melanin and that those effects are more pronounced than those of arbutin. It was also found that [6]-shogaol decreased the protein expression levels of tyrosinase-related protein 1 (TRP-1) and microphthalmia-associated transcriptional factor (MITF). In addition, the MITF mRNA levels were also effectively decreased in the presence of 20 μM [6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1-inhibitor (U0126) or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor) (LY294002). Further immunofluorescence staining assay implied the involvement of the proteasome in the downregulation of MITF by [6]-shogaol. Our confocal assay results also confirmed that [6]-shogaol inhibited α-melanocyte stimulating hormone- (α-MSH-) induced melanogenesis through the acceleration of extracellular responsive kinase (ERK) and phosphatidylinositol-3-kinase- (PI3K/Akt-) mediated MITF degradation.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, College of Health Care, China Medical University, Taichung, Taiwan.
authors.forename: Huey-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Applied Cosmetology and Master Program of Cosmetic Sciences, Hung Kuang University, Taichung, Taiwan.
authors.forename: Chia-Yin
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Applied Cosmetology and Master Program of Cosmetic Sciences, Hung Kuang University, Taichung, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Ke
authors.affiliation: Department of Applied Cosmetology and Master Program of Cosmetic Sciences, Hung Kuang University, Taichung, Taiwan.
authors.forename: Tsong-Min
authors.initials: TM
authors.lastname: Chang
mesh_terms: D000818:Animals; D002396:Catechols / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism*
chemical_list: D002396:Catechols; D004791:Enzyme Inhibitors; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D012333:RNA, Messenger; D000521:alpha-MSH; C040115:shogaol; D019869:Phosphatidylinositol 3-Kinases