Flavonoids as phospholipase A(2) inhibitors: Importance of their structure for selective inhibition of group II phospholipase A(2)

The inhibitory effect of the plant flavonoid, rutin, on group I phospholipase A(2) (PLA(2)-I) from porcine pancreas and Naja naja, and on group II phospholipase A(2), (PLA(2)-II) from Vipera russelli and Crotalus atrox was investigated. Rutin efficiently inhibited PLA(2)-II from both Vipera russelli and Crotalus atrox but was only a weak inhibitor of PLA(2)-I from porcine pancreas and Naja naja. The lack of strong inhibition of pancreatic PLA(2)-I was not due to contaminating proteins in the enzyme preparation, since the same weak inhibition was obtained against pancreatic PLA(2) purified to homogeneity as judged by two-dimensional gel electrophoresis. Rutin also efficiently inhibited human PLA(2)-II from synovial fluid but was only a weak inhibitor of human PLA(2)-I from pancreatic juice, suggesting that rutin is a selective PLA(2)-II inhibitor. A number of structurally similar flavonoids were tested for their ability to inhibit PLA(2)-II from Crotalus atrox and, for comparison, PLA(2)-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 PLA(2) activity, and that the hydroxyl groups in 3'- and 4'-position are required for selective inhibition of PLA(2)-II.