Inhibition of c-Kit signaling by diosmetin isolated from Chrysanthemum morifolium

• Published in: Archives of pharmacal research Vol. 37; no. 2; pp. 175 - 185
• Main Authors: Lee, Seong Jin, Jung, Tae-Hoon, Kim, Hojeong, Jeong, Daeyoung, Choi, Gildon, Park, Woo-Kyu, Kong, Jae Yang, Jin, Mu-Hyun, Cho, Heeyeong
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2014; 대한약학회
• Subjects: Animals; apigenin; Blotting, Western; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation - drug effects; Chrysanthemum - chemistry; Chrysanthemum morifolium; Flavonoids - isolation & purification; Flavonoids - pharmacology; Flowers - chemistry; fluorescence; Fluoroimmunoassay; Humans; luteolin; Medicine; melanin; Melanins - antagonists & inhibitors; Melanins - biosynthesis; melanocytes; Melanocytes - drug effects; Melanocytes - metabolism; Melanocytes - radiation effects; melanogenesis; Mice; Microscopy, Phase-Contrast; Models, Biological; Pharmacology/Toxicology; Pharmacy; phosphorylation; plant extracts; Proto-Oncogene Proteins c-kit - antagonists & inhibitors; Proto-Oncogene Proteins c-kit - genetics; Research Article; Sf9 Cells; Signal Transduction - drug effects; Spodoptera; stem cell factor; Stem Cell Factor - pharmacology; Stem Cell Factor - physiology; toxicity; Ultraviolet Rays; 약학; Diosmetin; c-Kit; Flavonoid; Depigmentation
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-013-0158-7

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.