Effect of thielocin A1 beta on bee venom phospholipase A2-induced edema in mouse paw

Several investigators have reported that inactivation of secretory phospholipase A2 purified from bee venom with p-bromophenacyl bromide, an irreversible inhibitor, before injection resulted in attenuation of the subsequent inflammatory reaction in the mouse paw edema model. Recently, thielocin A1 beta, a novel secretory phospholipase A2 inhibitor from fungi, was found to suppress histamine release from mast cells stimulated with secretory phospholipase A2. These observations led us to examine the effect of thielocin A1 beta against secretory phospholipase A2-induced paw edema. Thielocin A1 beta inhibited bee venom phospholipase A2 in a dose-dependent manner (IC50 = 1.4 microM). In addition, the inhibition of bee venom phospholipase A2 was noncompetitive (Ki = 0.57 microM) and reversible. Subplantar injection of bee venom phospholipase A2 produced a rapid but transient edematous response. Coinjection of thielocin A1 beta (1 microgram/paw) with bee venom phospholipase A2 resulted in a 44.7 +/- 4.6% reduction of edema formation. This anti-edema action was not enhanced by cyproheptadine (antihistamine/antiserotonin). These results suggest that thielocin A1 beta shows edema-reducing activity via inhibition of the phospholipase A2 activity which participates in histamine release by mast cells.