Inhibition of mammalian collagenase, matrix metalloproteinase-1, by naturally-occurring flavonoids

被引:86
作者
Lim, Hyun [1 ]
Kim, Hyun Pyo [1 ]
机构
[1] Kangwon Natl Univ, Coll Pharm, Chunchon 200701, South Korea
关键词
flavonoid; matrix metalloproteinase; activator protein-1; mitogen-activated protein kinase; skin inflammation;
D O I
10.1055/s-2007-990220
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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.
引用
收藏
页码:1267 / 1274
页数:8
相关论文
共 30 条
[1]   Lipopolysaccharide enhancement of 12-o-tetradecanoylphorbol 13-acetate-mediated transformation in rat glioma C6, accompanied by induction of inducible nitric oxide synthase [J].
Chen, TJ ;
Shen, SC ;
Lin, HY ;
Chien, LL ;
Chen, YC .
TOXICOLOGY LETTERS, 2004, 147 (01) :1-13
[2]  
Choe TB, 2003, J COSMET SCI, V54, P229
[3]  
Fisher G J, 1998, J Investig Dermatol Symp Proc, V3, P61
[4]   Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo [J].
Fisher, GJ ;
Talwar, HS ;
Lin, JY ;
Lin, PP ;
McPhillips, F ;
Wang, ZQ ;
Li, XY ;
Wan, YS ;
Kang, SW ;
Voorhees, JJ .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (06) :1432-1440
[5]   Luteolin, a flavonoid, inhibits AP-1 activation by basophils [J].
Hirano, T ;
Higa, S ;
Arimitsu, J ;
Naka, T ;
Ogata, A ;
Shima, Y ;
Fujimoto, M ;
Yamadori, T ;
Ohkawara, T ;
Kuwabara, Y ;
Kawai, M ;
Matsuda, H ;
Yoshikawa, M ;
Maezaki, N ;
Tanaka, T ;
Kawase, I ;
Tanaka, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 340 (01) :1-7
[6]  
Ishiwa J, 2000, J RHEUMATOL, V27, P20
[7]   Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo [J].
Kang, S ;
Chung, JH ;
Lee, JH ;
Fisher, GJ ;
Wan, YS ;
Duell, EA ;
Voorhees, JJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2003, 120 (05) :835-841
[8]   Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts [J].
Kim, HH ;
Shin, CM ;
Park, CH ;
Kim, KH ;
Cho, KH ;
Eun, HC ;
Chung, JH .
JOURNAL OF LIPID RESEARCH, 2005, 46 (08) :1712-1720
[9]  
KIM HK, 1995, J IMMUNOL, V154, P4741
[10]   Anti-inflammatory plant flavonoids and cellular action mechanisms [J].
Kim, HP ;
Son, KH ;
Chang, HW ;
Kang, SS .
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2004, 96 (03) :229-245