期刊
PLANTA MEDICA
卷 73, 期 12, 页码 1267-1274出版社
GEORG THIEME VERLAG KG
DOI: 10.1055/s-2007-990220
关键词
flavonoid; matrix metalloproteinase; activator protein-1; mitogen-activated protein kinase; skin inflammation
资金
- National Research Foundation of Korea [핵06B3405] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Some plant flavonoids in the form of whole plant extracts have been used topically for skin inflammatory disorders. Since matrix metalloproteinase-1 (MMP-1, collagenase-1) plays an important role in unbalanced turn-over or rapid breakdown of Collagen molecules in human inflamed/UV-irradiated skin, the effects of natural flavonoids on MMP-1 activity and MMP-1 expression were studied to establish the therapeutic potential. Against recombinant human MMP-1, flavonols such as quercetin and kaempferol were strong inhibitors with IC50 values of 39.6 and 43.7 mu M, respectively, while flavones such as apigenin and wogonin showed only weak inhibitory activity. In addition, quercetin, kaempferol, apigenin and wogonin (12.5 - 25.0 mu M) strongly inhibited MMP-1 induction in 12-O-tetradecanoylphorbol 13-acetate-treated human dermal fibroblasts, but naringenin (a flavanone) did not. By means of the electrophoretic mobility shift assay, these flavonoids were also found to inhibit activation of the transcription factor, activator protein-1 (AP-1). Moreover, quercetin inhibited extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) activation, and kaempferol inhibited p38 MAPK and c-Jun N-terminal kinase (JNK) activation among the MAPI(s tested. In contrast, flavones and naringenin did not inhibit the activation of these three MAPI(s. These results have shown, for the first time, that naturally-occurring flavonoids (quercetin, kaempferol, apigenin and wogonin) inhibit MMP-1 and down-regulate MMP-1 expression via an inhibition of the AP-1 activation although the cellular inhibitory mechanisms differ depending on their chemical structures. Therefore, certain plant flavonoids or plant extracts with these flavonoids as major components may be beneficial to treat some skin inflammatory disorders and to protect skin from photoaging.
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