Effect of flavones on rat brain and lung matrix metalloproteinase activity measured by film in-situ zymography.
We have evaluated the inhibitory activity of flavone, nobiletin, and heptamethoxyflavone on matrix metalloproteinase (MMP) activity in the rat. MMP in 9000-g supernatant fraction of lung homogenate was activated by p-aminophenyl mercuric acetate (APMA), and gelatinolytic activity was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by Coomassie staining. This activity should be related to MMP-2 and/or MMP-9 and was confirmed by gelatin zymography. Fluorescent-conjugated collagen used as a substrate for collagenolytic activity wasinvestigated by SDS-PAGE also. The film in-situ zymography method was applied to rat brain and lung tissue in the same manner. Flavone and nobiletin inhibited the APMA-stimulated gelatinolytic activity and also the collagenolytic activity by more than 75%. The film in-situ zymography method indicated that these compounds might be potent inhibitors of MMP, suggesting the specific inhibition of localized MMP in brain hippocampus and/or lung terminal bronchioles, which may contribute to the prevention of some types of brain disease or cancer invasion and metastasis.
Sasaki
K
K
Tohoku Pharmaceutical University, 4-1 Komatsushima 4-chome, Aoba-ku, Sendai 981-8558, Japan. kenrs@tohoku-pharm.ac.jp
Tateoka
N
N
Ando
H
H
Yoshizaki
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005780:Gelatin / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D047309:Flavones; D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; C059294:3,3',4',5,6,7,8-heptamethoxyflavone; D005780:Gelatin; D003094:Collagen; C008661:nobiletin; D020782:Matrix Metalloproteinases; C043562:flavone