Geniposide enhances melanogenesis by stem cell factor/c-Kit signalling in norepinephrine-exposed normal human epidermal melanocyte

Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):88-93. doi: 10.1111/j.1742-7843.2008.00251.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Enzyme-Linked Immunosorbent Assay
  • Epidermal Cells*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flow Cytometry
  • Humans
  • Iridoids / pharmacology*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Melanins / metabolism*
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Norepinephrine / pharmacology*
  • Oxidoreductases / physiology
  • Phosphorylation
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-kit / physiology*
  • Signal Transduction
  • Stem Cell Factor / antagonists & inhibitors
  • Stem Cell Factor / physiology*

Substances

  • Iridoids
  • Melanins
  • Stem Cell Factor
  • geniposide
  • Oxidoreductases
  • tyrosinase-related protein-1
  • Proto-Oncogene Proteins c-kit
  • Extracellular Signal-Regulated MAP Kinases
  • Norepinephrine