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 (0.18 J/cm2, 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.
Bibliographical noteFunding Information:
This study was supported by a grant from the BioGreen21 Program (Nos. 20070301-034-027 and 042 ) of the Rural Development Administration; World Class University Program ( R31-2008-00-10056-0 ) and Priority Research Centers Program ( 2009-0093824 ), the National Research Foundation of Korea, the Ministry of Education, Science, and Technology, Republic of Korea. Work was also supported by The Hormel Foundation and NIH grants CA120388 , R37CA081064 , CA077646 , CA027502 , and CA111536 .