Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf.
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.
Jung
Sung Keun
SK
Department of Agricultural Biotechnology, Seoul National University, Republic of Korea.
Lee
Ki Won
KW
Kim
Ho Young
HY
Oh
Mi Hyun
MH
Byun
Sanguine
S
Lim
Sung Hwan
SH
Heo
Yong-Seok
YS
Kang
Nam Joo
NJ
Bode
Ann M
AM
Dong
Zigang
Z
Lee
Hyong Joo
HJ
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
D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; C040015:myricetin; D048490:raf Kinases; D020780:Matrix Metalloproteinase 9