Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf

Sung Keun Jung, Ki Won Lee, Ho Young Kim, Mi Hyun Oh, Sanguine Byun, Sung Hwan Lim, Yong Seok Heo, Nam Joo Kang, Ann M. Bode, Zigang Dong, Hyong Joo Lee

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

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 (0.18 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.

Original languageEnglish (US)
Pages (from-to)1455-1461
Number of pages7
JournalBiochemical Pharmacology
Volume79
Issue number10
DOIs
StatePublished - May 15 2010

Bibliographical note

Funding 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 .

Keywords

  • Anti-wrinkle
  • Myricetin
  • Photoaging
  • Raf
  • UVB

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