1. Evidence that geniposide abrogates norepinephrine-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in melanocyte.
- Author
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Wen-Jun L, Hai-Yan W, Wei L, Ke-Yu W, and Rui-Ming W
- Subjects
- Cell Line, Flow Cytometry, Glucagon-Like Peptide-1 Receptor, Humans, Hypopigmentation metabolism, Iridoids isolation & purification, Keratinocytes drug effects, Keratinocytes metabolism, Medicine, Chinese Traditional, Melanocytes drug effects, Melanocytes metabolism, Norepinephrine, Proto-Oncogene Proteins c-kit drug effects, Receptors, Glucagon drug effects, Receptors, Glucagon metabolism, Signal Transduction drug effects, Up-Regulation drug effects, Vitiligo drug therapy, Vitiligo metabolism, Gardenia chemistry, Hypopigmentation drug therapy, Iridoids pharmacology, Proto-Oncogene Proteins c-kit metabolism
- Abstract
Geniposide (GP) as an agonist of glucagon-like peptide-1 receptor (GLP-1R) is an iridoid glycoside from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of vitiligo vulgaris. Interaction of c-kit receptor with its ligand-SCF potent enhances the melanocytic melanogenesis, which can be repressed by norepinephrine (NE). To discover economic and efficient drug against vitiligo vulgaris, this paper addresses the action and mechanism of GP abrogating the NE-induced hypopigmentation in melanocyte. Flow cytometry exhibited the up-regulation effect of GP on NE-suppressed production of c-kit by normal human epidermal melanocyte (HEMn) in a concentration-dependent manner, and exendin-(9-39) (selective GLP-1R antagonist) appeared to alleviate the GP-stimulated expression of c-kit. However, neither NE nor GP affected the production of SCF by normal human epidermal keratinocyte (HEKn) assessed by cellular enzyme-linked immunosorbent assay. Spectrophotometry documented that GP abrogated the repression effect of NE on tyrosinase activity and melanin production in HEMn in the presence of recombination SCF significantly. The response of melanocytic melanogenesis to GP was blocked by exendin-(9-39) or K44.2 antibody (c-kit inhibitory antibody). Data from this paper provide the evidence that GP abrogates the NE-induced hypopigmentation by the activation of GLP-1R-dependent c-kit receptor signaling in which c-kit expression is augmented in HEMn.
- Published
- 2008
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