Anti-Inflammatory Activity of Oleanolic Acid by Inhibition of Secretory Phospholipase A2

Oleanolic acid, a triterpenoid known for its anti-inflammatory properties, is commonly present in several medicinal plants. The present study evaluated the effect of oleanolic acid on sPLA 2 , a key enzyme in inflammatory reactions. Oleanolic acid inhibited sPLA 2 activities of human synovial fluid (HSF), human pleural fluid (HPF) and Vipera russelli (VRV-PL-V) and Naja naja (NN-PL-I) snake venoms in a concentration-dependent manner. The IC 50 values of sPLA 2 from these sources ranged from 3.08 to 7.78 μ M. Increasing calcium (Ca 2+ ) concentrations from 2.5 to 15 mM and substrate concentration up to 180 nM did not affect the level of inhibition. Oleanolic acid enhanced the relative intrinsic fluorescence intensity of sPLA 2 (VRV-PL-V). In the presence of oleanolic acid, an apparent shift in the far UV-CD spectrum of sPLA 2 was observed. These studies indicate direct interaction with the enzyme and formation of an sPLA 2 -oleanolic acid complex. The complex formed resulted in irreversible inhibition of sPLA 2 . Oleanolic acid inhibited indirect hemolytic activity and mouse paw edema induced by sPLA 2 . Inhibition of in vitro and in vivo sPLA 2 activity by oleanolic acid explains the observed anti-inflammatory properties of several oleanolic acid-containing medicinal plants. Abbreviations COX.1/2:cyclooxygenase-1/2 HPF:human pleural fluid HSF:human synovial fluid LOX:lipoxygenase NN-PL-I: Naja naja phospholipase-I PAF:platelet activation factor p -BPB: para -bromophenacyl bromide sPLA 2 :secretory phospholipase A 2 UV-CD:ultraviolet circular dichroism VRV-PL-V: Vipera russelli venom phospholipase-V