title: Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf.
abstract: Chronic exposure to solar ultraviolet (UV) light causes skin photoaging. Many studies have shown that naturally occurring phytochemicals have anti-photoaging effects, but their direct target molecule(s) and mechanism(s) remain unclear. We found that myricetin, a major flavonoid in berries and red wine, inhibited wrinkle formation in mouse skin induced by chronic UVB irradiation (0.18J/cm(2), 3 days/week for 15 weeks). Myricetin treatment reduced UVB-induced epidermal thickening of mouse skin and also suppressed UVB-induced matrix metalloproteinase-9 (MMP-9) protein expression and enzyme activity. Myricetin appeared to exert its anti-aging effects by suppressing UVB-induced Raf kinase activity and subsequent attenuation of UVB-induced phosphorylation of MEK and ERK in mouse skin. In vitro and in vivo pull-down assays revealed that myricetin bound with Raf in an ATP-noncompetitive manner. Overall, these results indicate that myricetin exerts potent anti-photoaging activity by regulating MMP-9 expression through the suppression of Raf kinase activity.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Republic of Korea.
authors.forename: Sung Keun
authors.initials: SK
authors.lastname: Jung
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Oh
authors.forename: Sanguine
authors.initials: S
authors.lastname: Byun
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Lim
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.forename: Nam Joo
authors.initials: NJ
authors.lastname: Kang
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D047468:Immunoprecipitation; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008812:Mice, Hairless; D008813:Mice, Inbred ICR; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048490:raf Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; C040015:myricetin; D048490:raf Kinases; D020780:Matrix Metalloproteinase 9