title: Flavonoids as phospholipase A2 inhibitors: importance of their structure for selective inhibition of group II phospholipase A2.
abstract: The inhibitory effect of the plant flavonoid, rutin, on group I phospholipase A2 (PLA2-I) from porcine pancreas and Naja naja, and on group II phospholipase A2 (PLA2-II) from Vipera russelli and Crotalus atrox was investigated. Rutin efficiently inhibited PLA2-II from both Vipera russelli and Crotalus atrox but was only a weak inhibitor of PLA2-I from porcine pancreas and Naja naja. The lack of strong inhibition of pancreatic PLA2-I was not due to contaminating proteins in the enzyme preparation, since the same weak inhibition was obtained against pancreatic PLA2 purified to homogeneity as judged by two-dimensional gel electrophoresis. Rutin also efficiently inhibited human PLA2-II from synovial fluid but was only a weak inhibitor of human PLA2-I from pancreatic juice, suggesting that rutin is a selective PLA2-I from porcine pancreas. The results obtained indicate that the hydroxyl group in 5-position as well as the double bond and the double-bonded oxygen in the oxane ring are all important for the overall ability of flavonoids to inhibit PLA2 activity, and that the hydroxyl groups in 3'- and 4'- position are required for selective inhibition of PLA2-II.
authors.affiliation: Department of Occupational and Environmental Medicine Faculty of Health Sciences, University of Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lindahl
authors.forename: C
authors.initials: C
authors.lastname: Tagesson
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017839:Crotalus; D017815:Elapidae; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D010179:Pancreas / Q000201:enzymology; D010189:Pancreatic Juice / Q000201:enzymology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000145:classification; D054467:Phospholipases A2; D017840:Daboia; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D013582:Synovial Fluid / Q000201:enzymology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D018836:Inflammation Mediators; D012431:Rutin; D010741:Phospholipases A; D054467:Phospholipases A2