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

Myricetin inhibited UVB-induced wrinkle formation and MMP-9 expression by directly inhibiting Raf kinase activity in mouse skin. Chronic exposure to solar ultraviolet (UV) light causes skin photoaging. Many studies have shown that naturally occurring phytochemicals have anti-photoaging effects, but...

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Veröffentlicht in:Biochemical pharmacology 2010-05, Vol.79 (10), p.1455-1461
Hauptverfasser: Jung, Sung Keun, Lee, Ki Won, Kim, Ho Young, Oh, Mi Hyun, Byun, Sanguine, Lim, Sung Hwan, Heo, Yong-Seok, Kang, Nam Joo, Bode, Ann M., Dong, Zigang, Lee, Hyong Joo
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container_end_page 1461
container_issue 10
container_start_page 1455
container_title Biochemical pharmacology
container_volume 79
creator Jung, Sung Keun
Lee, Ki Won
Kim, Ho Young
Oh, Mi Hyun
Byun, Sanguine
Lim, Sung Hwan
Heo, Yong-Seok
Kang, Nam Joo
Bode, Ann M.
Dong, Zigang
Lee, Hyong Joo
description Myricetin inhibited UVB-induced wrinkle formation and MMP-9 expression by directly inhibiting Raf kinase activity in mouse skin. 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/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.
doi_str_mv 10.1016/j.bcp.2010.01.004
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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/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. 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Drug treatments ; Photoaging ; Raf ; raf Kinases - antagonists &amp; inhibitors ; raf Kinases - physiology ; Skin Aging - drug effects ; Skin Aging - radiation effects ; Skin involvement in other diseases. Miscellaneous. General aspects ; Ultraviolet Rays - adverse effects ; UVB</subject><ispartof>Biochemical pharmacology, 2010-05, Vol.79 (10), p.1455-1461</ispartof><rights>2010 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>2010 Elsevier Inc. All rights reserved.</rights><rights>2010 Elsevier Inc. 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Overall, these results indicate that myricetin exerts potent anti-photoaging activity by regulating MMP-9 expression through the suppression of Raf kinase activity.</description><subject>Animals</subject><subject>Anti-wrinkle</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Dermatology</subject><subject>Epidermis - drug effects</subject><subject>Epidermis - enzymology</subject><subject>Epidermis - radiation effects</subject><subject>Female</subject><subject>Flavonoids - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>Immunoprecipitation</subject><subject>Matrix Metalloproteinase 9 - biosynthesis</subject><subject>Matrix Metalloproteinase Inhibitors</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Hairless</subject><subject>Mice, Inbred ICR</subject><subject>Myricetin</subject><subject>Pharmacology. Drug treatments</subject><subject>Photoaging</subject><subject>Raf</subject><subject>raf Kinases - antagonists &amp; inhibitors</subject><subject>raf Kinases - physiology</subject><subject>Skin Aging - drug effects</subject><subject>Skin Aging - radiation effects</subject><subject>Skin involvement in other diseases. Miscellaneous. 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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/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. 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subjects Animals
Anti-wrinkle
Biological and medical sciences
Blotting, Western
Dermatology
Epidermis - drug effects
Epidermis - enzymology
Epidermis - radiation effects
Female
Flavonoids - pharmacology
Gene Expression - drug effects
Immunoprecipitation
Matrix Metalloproteinase 9 - biosynthesis
Matrix Metalloproteinase Inhibitors
Medical sciences
Mice
Mice, Hairless
Mice, Inbred ICR
Myricetin
Pharmacology. Drug treatments
Photoaging
Raf
raf Kinases - antagonists & inhibitors
raf Kinases - physiology
Skin Aging - drug effects
Skin Aging - radiation effects
Skin involvement in other diseases. Miscellaneous. General aspects
Ultraviolet Rays - adverse effects
UVB
title Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf
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