Interaction of aristolochic acid with Vipera russelli phospholipase A2: its effect on enzymatic and pathological activities

Aristolochic acid, an alkaloid from the plant Aristolochia species, interacts with the major basic phospholipase A2 from Vipera russelli venom. It is an uncompetitive inhibitor with a Ki of 9.9 X 10(-4)M when phosphatidylcholine is used as substrate. The inhibition of direct and indirect hemolysis is higher compared to the inhibition of phosphatidylcholine hydrolysis. Edema-inducing activity of Vipera russelli phospholipase A2 is inhibited by aristolochic acid when injected either as a mixture or separately. Both i.m. and i.p. administration of aristolochic acid following phospholipase injection are equally effective in inhibiting edema. The alkaloid inhibits the edema-inducing activity as soon as it reaches the site, but does not aid in recovery. Aristolochic acid failed to inhibit other pathological activities of the enzyme.