title: Geniposide enhances melanogenesis by stem cell factor/c-Kit signalling in norepinephrine-exposed normal human epidermal melanocyte.
abstract: Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of generalized vitiligo. Stem cell factor from keratinocyte recognizes and activates its receptor c-kit carried by melanocyte to potent enhance melanocytic melanogenesis that can be suppressed by norepinephrine. This study addresses the action and mechanism of geniposide enhancing melanogenesis in norepinephrine-exposed normal human epidermal melanocyte. Flow cytometry results from this study exhibited the augmentation effect of geniposide on production of c-kit receptor by norepinephrine-exposed normal human epidermal melanocyte. However, geniposide did not affect the production of stem cell factor by norepinephrine-exposed normal human epidermal keratinocyte assessed by cellular enzyme-linked immunosorbent assay (ELISA). ELISA indicated that at the presence of stem cell factor, geniposide was capable of elevating the level of extracellular signal-regulated kinase 1/2 phosphorylation within norepinephrine-exposed normal human epidermal melanocyte, which is known to be involved in stem cell factor/c-kit downstream signalling. And inhibition of c-kit with inhibitory antibody K44.2 completely blocked the increase in geniposide-stimulated extracellular signal-regulated kinase 1/2 phosphorylation. In addition, spectrophotometry demonstrated the enhancement effect of geniposide on melanogenesis (tyrosinase activity and melanin production) in norepinephrine-exposed normal human epidermal melanocyte at the presence of stem cell factor, which was blocked by c-kit inhibitory antibody K44.2. Data from this study suggest that geniposide can enhance melanogenesis by stem cell factor/c-kit signalling in which the expression of c-kit receptor is augmented in norepinephrine-exposed normal human epidermal melanocyte.
authors.affiliation: Laboratory for Drug Discovery, Shandong Institute of Light Industry, Jinan, China. lanwenjun0522@sina.com
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Lan
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lan
authors.forename: Ke-Yu
authors.initials: KY
authors.lastname: Wang
mesh_terms: D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010088:Oxidoreductases / Q000502:physiology; D010766:Phosphorylation; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D039823:Iridoids; D008543:Melanins; D019089:Stem Cell Factor; C007835:geniposide; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D019009:Proto-Oncogene Proteins c-kit; D048049:Extracellular Signal-Regulated MAP Kinases; D009638:Norepinephrine