Effects of aristolochic acid on phospholipase A 2 activity and arachidonate metabolism of human neutrophils

Abstract

Aristolochic acid is an alkaloid which has recently been shown to have anti-inflammatory activity against edema in mouse foot pads induced by phospholipases A 2 from human synovial fluid. The present study has investigated the effects of aristolochic acid on phospholipase activity and arachidonic acid mobilization in human neutrophils. We find that aristolochic acid is a dose-dependent inhibitor of the calcium-dependent neutral active phospholipase A 2 isolated from human neutrophils. As much as 90% of the A23187-stimulated release of previously incorporated [ 3H]arachidonate from intact neutrophils is inhibited by aristolochic acid; the effect is dose-dependent, with an IC 50 of 40 μM, and quite rapid, with near maximal inhibition within 5 min. Aristolochic acid inhibits the A23187-stimulated loss of [ 3H]arachidonate from both choline- and inositol-phospholipids. Decreased release of free [ 3H]arachidonate is accompanied by a concominant decrease in synthesis of [ 3]]leukotriene B 4 and [ 3H]hydroxyeicosatetraenoic acids. Furthermore, aristolochic acid also inhibits the A23187-stimulated synthesis of [ 3H]alkylacetylglycerophosphocholine from cellular [ 3H]alkylacylglycerophosphocholine. These results indicate that aristolochic acid is an effective inhibitor of the A23187-stimulated phospholipase A 2 activity in human neutrophils.