Document Detail


Group IIA secretory PLA2 inhibition by ursolic acid: a potent anti-inflammatory molecule.
MedLine Citation:
PMID:  17456043     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) isolated from many medicinal plants has diverse pharmacologically important properties, including strong anti-inflammatory activity. However its interaction with pro-inflammatory PLA2 is not known. Ursolic acid inhibited secretory PLA2 (sPLA2) enzymes purified from Vipera russelli, Naja naja venom and human pleural fluid and synovial fluid. IC50 values determined for these enzymes ranged from 12 to 18 microM. Group II secretory PLA2 from both venoms & human inflammatory source were found to be sensitive to inhibition in comparison with group I cobra venom sPLA2. Variation in Ca2+ concentration from 2.5-15 mM did not alter the level of inhibition. Similarly sPLA2 inhibition by ursolic acid is independent of substrate concentration. Ursolic acid interacts with purified venom sPLA2 enzymes and enhances relative fluorescence intensity in a dose dependent manner. In the presence of ursolic acid apparent shift in the far UV-CD spectra of sPLA2 was observed, indicating a direct interaction with the enzyme and formation of enzyme-ursolic acid complex. This complex results in irreversible inhibition of sPLA2 as evident by dialysis study. Inhibition of sPLA2 induced mouse paw edema and indirect hemolytic activity confirmed its sPLA2 inhibitory activity in vivo and in situ respectively. These studies revealed that the strong anti-inflammatory activity of ursolic acid is by inhibiting sPLA2 enzymes.
Authors:
A Nataraju; C D Raghavendra Gowda; R Rajesh; B S Vishwanath
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current topics in medicinal chemistry     Volume:  7     ISSN:  1873-4294     ISO Abbreviation:  Curr Top Med Chem     Publication Date:  2007  
Date Detail:
Created Date:  2007-04-25     Completed Date:  2007-05-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101119673     Medline TA:  Curr Top Med Chem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  801-9     Citation Subset:  IM    
Affiliation:
Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore-570 006, Karnataka, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents / pharmacology
Calcium / pharmacology
Edema / drug therapy
Enzyme Inhibitors / therapeutic use*
Group II Phospholipases A2
Hemolysis / drug effects
Humans
Inhibitory Concentration 50
Mice
Phospholipases A / antagonists & inhibitors*,  isolation & purification
Phospholipases A2
Pleural Cavity / enzymology
Snake Venoms
Spectrum Analysis
Synovial Fluid / enzymology
Triterpenes / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Enzyme Inhibitors; 0/Snake Venoms; 0/Triterpenes; 7440-70-2/Calcium; 77-52-1/ursolic acid; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Group II Phospholipases A2; EC 3.1.1.4/Phospholipases A2

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