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 muM. 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.
Dharmappa
Kattepura K
KK
Department of Studies in Biochemistry, University of Mysore, Mysore, India.
Kumar
Raju Venkatesh
RV
Nataraju
Angaswamy
A
Mohamed
Riyaz
R
Shivaprasad
Holenarasipura V
HV
Vishwanath
Bannikuppe S
BS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D009828:Oleanolic Acid / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010994:Pleura / Q000187:drug effects; D012910:Snake Venoms / Q000201:enzymology; D013582:Synovial Fluid / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D012910:Snake Venoms; D009828:Oleanolic Acid; D054497:Phospholipases A2, Secretory; D002118:Calcium