Flavonoids as phospholipase A2 inhibitors: importance of their structure for selective inhibition of group II phospholipase A2

Inflammation. 1997 Jun;21(3):347-56. doi: 10.1023/a:1027306118026.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Crotalus
  • Elapidae
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators / antagonists & inhibitors
  • Molecular Structure
  • Pancreas / enzymology
  • Pancreatic Juice / enzymology
  • Phospholipases A / antagonists & inhibitors*
  • Phospholipases A / classification
  • Phospholipases A2
  • Russell's Viper
  • Rutin / chemistry
  • Rutin / pharmacology*
  • Structure-Activity Relationship
  • Swine
  • Synovial Fluid / enzymology

Substances

  • Antioxidants
  • Enzyme Inhibitors
  • Flavonoids
  • Inflammation Mediators
  • Rutin
  • Phospholipases A
  • Phospholipases A2