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

Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf.
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DOI:
10.1016/j.bcp.2010.01.004
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发表时间:
2010-05-15
影响因子:
5.8
通讯作者:
Lee, Hyong Joo
Lee, Hyong Joo
中科院分区:
医学2区
文献类型:
--
作者:
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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长期暴露于太阳紫外线(UV)光会导致皮肤光老化。许多研究表明,天然存在的植物化学物质具有抗光老化作用,但其直接靶分子和机制尚不清楚。我们发现,杨梅苷,浆果和红葡萄酒中的主要黄酮类化合物,抑制皱纹的形成,在小鼠皮肤诱导的慢性UVB照射(0.18 J/cm 2,3天/周,15周)。杨梅素治疗减少UVB诱导的小鼠皮肤表皮增厚,也抑制UVB诱导的基质金属蛋白酶-9(MMP-9)的蛋白表达和酶活性。杨梅素似乎通过抑制UVB诱导的Raf激酶活性和随后的UVB诱导的MEK和ERK磷酸化的衰减来发挥其抗衰老作用。在体外和体内的下拉实验表明,杨梅素结合Raf在ATP的非竞争性方式。总体而言,这些结果表明,杨梅素通过抑制Raf激酶活性调节MMP-9的表达发挥有效的抗光老化活性。
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/wk for 15 wk). 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.
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