title: Inhibition of c-Kit signaling by diosmetin isolated from Chrysanthemum morifolium.
abstract: The interaction of stem cell factor (SCF) with its cognate receptor c-Kit is closely associated with the survival and maturation of melanocytes. To investigate novel depigmentation agents, we screened 2,000 plant extracts for c-Kit inhibitors to identify active small molecules by using time-resolved fluorescence enzyme assays. For the active extracts identified as inhibitors of c-Kit enzyme, we evaluated the effects of the active extracts and isolated flavonoids on c-Kit phosphorylation in MO7e/melanocytes. Anti-melanogenic activity was also examined in melanocytes and melanoderm model. The flavonoids such as diosmetin, apigenin, acacetin and luteolin isolated from Chrysanthemum morifolium were found to be active in inhibiting c-Kit both at enzyme and cellular levels. In addition, these flavonoids attenuated SCF-induced proliferation of human primary melanocytes without toxicity and suppressed ultraviolet (UV) B irradiation-mediated melanin synthesis significantly. Among the active flavonoids, diosmetin was found to inhibit SCF-induced melanogenesis in a human melanoderm model. These results strongly suggest that C. morifolium extract and diosmetin have potential to suppress SCF-/UVB-induced melanogenesis, and could be developed as anti-pigmentation agents.
authors.affiliation: Pharmacology Research Group, Drug Discovery Division, Korea Research Institute of Chemical Technology, Gajeongno 141, Yuseong-gu, Daejeon, 305-343, Korea.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Hojeong
authors.initials: H
authors.lastname: Kim
authors.forename: Daeyoung
authors.initials: D
authors.lastname: Jeong
authors.forename: Gildon
authors.initials: G
authors.lastname: Choi
authors.forename: Woo-Kyu
authors.initials: WK
authors.lastname: Park
authors.forename: Jae Yang
authors.initials: JY
authors.lastname: Kong
authors.forename: Mu-Hyun
authors.initials: MH
authors.lastname: Jin
authors.forename: Heeyeong
authors.initials: H
authors.lastname: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D031202:Chrysanthemum / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry; D015200:Fluoroimmunoassay; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008858:Microscopy, Phase-Contrast; D008954:Models, Biological; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors* / Q000235:genetics; D061987:Sf9 Cells; D015398:Signal Transduction / Q000187:drug effects*; D018411:Spodoptera; D019089:Stem Cell Factor / Q000494:pharmacology / Q000502:physiology; D014466:Ultraviolet Rays
chemical_list: D005419:Flavonoids; D008543:Melanins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; C039602:diosmetin