Effects of flavonoids on Naja naja and human recombinant synovial phospholipases A2 and inflammatory responses in mice.
Six flavonoid derivatives were tested for their influence on Naja naja and human recombinant synovial phospholipase A2. They showed a selectivity for the last enzyme with IC50 = 14.3, 17.6, 12.2 and 28.2 microM for quercetagetin, kaempferol-3-O-galactoside, scutellarein and scutellarein-7-O-glucuronide, respectively, while reduced effects were observed for hispidulin and hibifolin. After topical application all the flavonoids inhibited 12-O-tetradecanoylphorbol-13-acetate-induced ear oedema in mice with a potency comparable to that of indomethacin and they were also able to inhibit carrageenan-induced mouse paw oedema at a dose of 150 mg/kg p.o. The blockade of the free hydroxyl at C-7 or C-6 reduced the anti-inflammatory activity and also the inhibitory effect on human recombinant synovial phospholipase A2. These results are in accordance with the notion that group II phospholipases A2 may play a role in experimental inflammation, although several mechanisms seems to be involved in the anti-inflammatory effect of this group of flavonoids.
Gil
B
B
Department of Pharmacology, University of Valencia, Spain.
Sanz
M J
MJ
Terencio
M C
MC
Ferrándiz
M L
ML
Bustos
G
G
Payá
M
M
Gunasegaran
R
R
Alcaraz
M J
MJ
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D005697:Galactosides / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D044949:Kaempferols; D008297:Male; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012911:Snakes; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D047310:Apigenin
D002867:Chromones; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D005697:Galactosides; D044949:Kaempferols; D010741:Phospholipases A; D054467:Phospholipases A2; D011794:Quercetin; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate; C066407:kaempferol-3-O-galactoside; C087346:hibifolin; C055957:hispidulin; C458179:scutellarein; D047310:Apigenin; C079163:quercetagetin