title: Effects of flavonoids on Naja naja and human recombinant synovial phospholipases A2 and inflammatory responses in mice.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Valencia, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Gil
authors.forename: M J
authors.initials: MJ
authors.lastname: Sanz
authors.forename: M C
authors.initials: MC
authors.lastname: Terencio
authors.forename: M L
authors.initials: ML
authors.lastname: Ferrándiz
authors.forename: G
authors.initials: G
authors.lastname: Bustos
authors.forename: M
authors.initials: M
authors.lastname: Payá
authors.forename: R
authors.initials: R
authors.lastname: Gunasegaran
authors.forename: M J
authors.initials: MJ
authors.lastname: Alcaraz
mesh_terms: 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
chemical_list: 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